7-9, 1994, the National Institute of Diabetes and
Digestive and Kidney Diseases, together with the Office of Medical
Applications of Research of the National Institutes of Health, convened
a Consensus Development Conference on Helicobacter pylori in Peptic
Ulcer Disease, cosponsored by the National Institute of Allergy and
Infectious Diseases, admitting that Helicobacter pylori infection is
the cause of gastritis and ulcers, and directing that "All patients
with gastric or duodenal ulcers who are infected with H. pylori should
be treated with antimicrobials regardless of whether they are suffering
from the initial presentation of the disease or from a recurrence."
(Perhaps not coincidentally, a few
weeks later on Feb. 21, 1994, Mary Lasker croaked.)
(Helicobacter pylori in peptic ulcer disease. NIH Consens Statement
Online 1994 Jan 7-9 [cited 2006-07-29] 12(1):1-23.)
working group on schistosomes, liver flukes and Helicobacter pylori of
the International Agency for Research on Cancer met in Lyon, France,
and issued a report concluding that "infections of humans with H.
pylori is causally associated with the risk of developing gastric
cancer" (Infection with Helicobacter pylori (Group 1). In: Vol. 61,
Schistosomes, Liver Flukes and Helicobacter pylori. IARC Monographs on
the Evaluation of Carcinogenic Risks to Humans, 7-14 June 1994).
"5.1 Exposure data ...H. pylori occurs worldwide and
causes a chronic infection which rarely resolves spontaneously. Its
prevalence is highest in developing countries and increases rapidly
during the first two decades of life, such that 80-90% of the
population may be infected by early adulthood. In most developed
countries, the prevalence of infection is substantially lower at all
ages, and especially in childhood. The prevalence increases gradually
throughout life up to the age of 70-80 years. The prevalence in both
developed and developing countries is higher among people in lower
socioeconomic classes and may be associated with crowding in childhood.
A progressive reduction in the rate of infection early in life of
people in successive birth cohorts has been observed in developed
"H. pylori causes gastritis
in all infected people. This is accompanied by a specific, systemic
immunoglobulin G response. Nevertheless, many such infections are
asymptomatic. In some people, the infection gives rise to duodenal or
gastric ulceration. The infection can be eradicated successfully with
several regimens in which different drugs are combined. Eradication of H. pylori resolves gastritis,
prevents recurrence of peptic ulcer disease and leads to a significant
decline in immunoglobulin response within six months."
"5.2 Human carcinogenicity data
Six studies in which estimates of prevalence of infection by H. pylori were related to estimates
of concurrent or earlier incidence of or mortality from cancer of the
stomach in five or fewer populations show no consistent association
between these variables. Significantly positive geographical
correlations were observed, however, in two larger studies in which the
ranges of cancer incidence and mortality were much wider: one in 46
rural populations in China and the other in 17 populations in Europe,
Japan and the USA. The populations of certain developing countries,
including many in Africa and some in Asia, have low rates of gastric
cancer; the prevalence of H. pylori
has been studied in some of these populations and is known to be high."
"The association between prior seropositivity for H. pylori and subsequent gastric
cancer has been evaluated in three cohort studies, yielding 29-109
cases of gastric cancer. Significant positive associations were
observed in all three, with estimated relative risks, based on
case-control analyses within the cohorts, varying from 2.8 to 6.0. In a
pooled analysis of the three studies, the relative risk was 3.8, which
was significant, and there was a significant trend towards increasing
estimated relative risks with increasing length of followup... Nine
retrospective case-control studies have addressed the association
between sero-prevalence for H. pylori
infection and incidence of gastric cancer. The estimated relative risks
for gastric cancer were evaluated in six studies, ranging from 1.2 to
4.2, and were significant in three studies. In a number of studies, the
control series may not have been representative of the population that
gave rise to the cases, either because of the method of sampling (e.g.
subjects requiring gastrointestinal investigation) or because of
exclusions on the basis of a history of gastric symptoms or disease."
"When appropriate stratifications of the results of the prospective
and retrospective studies were reported, the association between
infection with H. pylori and
gastric cancer was stronger in younger patients and for cancers at
sites other than the cardia. The association was similarly strong for
the intestinal and diffuse histological types of cancer."
"The association between H. pylori
infection and gastric lymphoma has been investigated in some studies.
In two series of 110 and 178 patients with gastric B-cell
mucosa-associated lymphoid tissue lymphomas, 92 and 98%, respectively,
had histological evidence of H.
pylori infection. In two studies of treatment, five of six
patients and 12 of 16 patients showed tumour regression after therapy
to eradicate H. pylori.
Thirty-three cases of gastric non-Hodgkins lymphoma were observed in a
cohort study of patients with H.
pylori infection in the USA and Norway, giving a significant
estimated relative risk of 6.3."
5.5 Evaluation There is sufficient evidence in humans for
the carcinogenicity of infection with Helicobacter
Overall Evaluation Infection with Helicobacter pylori is
carcinogenic to humans (Group 1).
Helicobacter pylori and ulcers: a paradigm revised. Nancy A. Lynch. Federation of American Societies for Experimental Biology (FASEB), Office of Public Affairs.Lynch / FASEB (pdf, 9pp)
Helicobacter pylori: epidemiology and routes of transmission. LM
Brown [of Biostatistics Branch, Division of Epidemiology and Genetics,
National Cancer Institute, National Institutes of Health, Bethesda,
MD]. Epidemiol Rev 2000;22(2):283-297. Review. "Most of the recent
studies found no significant association with current smoking or any
other measure of tobacco use (52, 55, 60, 66-68), and one recent study
from Japan (69) reported a significant negative association with
Pathogenesis of Helicobacter pylori infection. JG Kusters, AHM van
Vliet, EJ Kuipers. Clin Microbiol Rev 2006 July 1;19(3):449-490. Review.
Global burden of gastric cancer attributable to pylori. M Plummer, S Franceschi, J Vignat, D Forman, C de Martel. Int J Cancer 2015 Jan 15;136(2):487-490. "We previously estimated that 660,000 cases of cancer in the year 2008 were attributable to the bacterium Helicobacter pylori (H. pylori), corresponding to 5.2% of the 12.7 million total cancer cases that occurred worldwide. In recent years, evidence has accumulated that immunoblot (western blot) is more sensitive for detection of anti-H. pylori antibodies than ELISA, the detection method used in our previous analysis... Using the immunoblot-based data, the worldwide AF for H. pylori in [non-cardia gastric cancer] increased from 74.7% to 89.0%. This implies approximately 120,000 additional cases of NCGC attributable to H. pylori infection for a total of around 780,000 cases (6.2% instead of 5.2% of all cancers)."Plummer - Int J Cancer 2015 abstract / PubMed
Association between infection with Helicobacter pylori and risk of
gastric cancer: evidence from a prospective investigation. D Forman, DG
Newell, F Fullerton, JW Yarnell, AR Stacey, N Wald, F. Sitas. BMJ 1991
Jun 1;302(6788):1302-1305. "20 of the 29 cases (69%) and 54 of the 116
controls (47%) were positive for H pylori specific antibody. The median
specific IgG concentration was significantly higher in the cases than
controls (90 micrograms/ml v 3.6 micrograms/ml, p less than 0.01). The
estimated odds ratio for the risk of gastric cancer in those with a
history of infection with H pylori was 2.77 (95% confidence interval
1.04 to 7.97, 2p = 0.039)."
The association of Helicobacter pylori with gastric cancer and preneoplastic gastric lesions in Chiapas, Mexico. J Guarner, A Mohar, J Parsonnet, D Halperin. Cancer 1993 Jan 15;71(2):297-301. In 183 subjects tested by enzyme-linked immunosorbent assay (ELISA) for anti-H. pylori immunoglobulin G, "There was a strong association between H. pylori in the tissue and atrophy (relative risk, 15.0; 95% confidence interval, 4.2-56.6), intestinal metaplasia (relative risk, 5.7; 95% confidence interval, 1.9-16.8), and dysplasia or cancer (relative risk, 4.0; 95% confidence interval, 1.1-14.8)... In this high-risk population, precursor lesions for adenocarcinoma were associated universally with H. pylori infection."Guarner - Cancer 1993 abstract / PubMed
Helicobacter pylori, pepsinogen, and risk for gastric adenocarcinoma. J Parsonnet, IM Samloff, LM Nelson, N Orentreich, JH Vogelman, GD Friedman. Cancer Epidemiol Biomarkers Prev 1993 Sep-Oct;2(5):461-466. In 136 cases of gastric adenocarcinoma and 136 matched controls without adenocarcinoma from a large cohort that had contributed serum in the 1960's, "By univariate analysis, H. pylori infection [odds ratio (OR), 3.6; P < 0.001] and serum pepsinogen I < 50 ng/ml (OR = 2.9; P = 0.003) were both associated with development of distal cancer. In multivariate analysis, there was interaction between the two variables; H. pylori in the absence of low pepsinogen I was independently associated with cancer (OR, 2.4; P = 0.04) but low pepsinogen I in the absence of H. pylori infection was not associated with cancer (OR, 0.8; P > 0.5). In combination, however, H. pylori infection and a low pepsinogen I were associated with a marked increase in the risk of developing distal malignancy (OR, 10.0; P = 0.08)."Parsonnet - Cancer Epidemiol Biomarkers Prev 1993 abstract / PubMed
Helicobacter pylori infection: independent risk indicator of gastric
adenocarcinoma. LE Hansson, L Engstrand, O Nyren, DJ Evans Jr, A
Lindgren, R Bergstrom, B Andersson, L Athlin, O Bendtsen, P Tracz.
Gastroenterology 1993 Oct;105(4):1098-1103. In sera from 112 incident
gastric cancer patients and 103 control patients with
nongastroenterological diseases, "The odds ratio (OR) was 2.60 (95%
confidence interval, 1.35-5.02). The increased OR associated with H.
pylori infection was confined to tumors with a noncardia location (OR,
3.06) and men (OR, 4.27). OR increased with decreasing age at cancer
diagnosis to reach 9.33 in patients < 60 years of age."
Helicobacter pylori infection in a randomly selected population,
healthy volunteers, and patients with gastric ulcer and gastric
adenocarcinoma. A seroprevalence study in Taiwan. JT Lin, JT Wang, TH
Wang, MS Wu, TK Lee, CJ Chen. Scand J Gastroenterol 1993
Dec;28(12):1067-72. In serum IgG antibodies of 823 randomly selected
subjects, 92 healthy volunteers, 117 patients with gastric ulcer, and
148 with gastric adenocarcinomas, "Gastric ulcer patients had a higher
seropositivity (83.8%) than healthy volunteers (62.0%) and gastric
adenocarcinoma patients (62.2%) (P < 0.001). Gender difference,
blood type, and habit of smoking were not associated with the
seroprevalence in any study groups. Gastric ulcer coexistent with
duodenal ulcer had a higher seropositivity (94.7%) (P < 0.05). The
seropositivity of H. pylori in gastric adenocarcinoma patients was
higher than in healthy volunteers only in younger age and was not
associated with histologic type, invasion, and location of major
Serum anti-Helicobacter pylori antibody and gastric carcinoma among
young adults. Research Group on Prevention of Gastric Carcinoma among
Young Adults. S Kikuchi, O Wada, T Nakajima, T Nishi, O Kobayashi, T
Konishi, Y Inaba. Cancer 1995 Jun 15;75(12):2789-2793. For serum IgG to
HP in 105 hospitalized patients younger than 40, 102 hospital controls,
and 101 screening controls, "The OR (95% confidence interval) was 13.3
(5.3-35.6). For women, the OR was 32.8, whereas for men it was 6.8. The
OR for patients with early gastric carcinoma was 20.8, and for patients
with advanced disease, it was 10.8. The OR for intestinal-type
carcinoma was 18.0, and for diffuse-type carcinoma, it was 12.8. The OR
for proximal carcinoma was 11.3, and for distal carcinoma it was 14.8.
CONCLUSION: The OR for these young subjects was considerably larger
than that for the older subjects in previously published studies."
IgG immune response to Helicobacter pylori antigens in patients with
gastric cancer as defined by ELISA and immunoblotting. K Klaamas, M
Held, T Wadstrom, A Lipping, O Kurtenkov. Int J Cancer 1996 Jul
3;67(1):1-5. In 182 gastric cancer patients and 306 blood donor
controls in Estonia, "A significantly higher H. pylori seroprevalence
was found in patients in the early stages of tumor development compared
with both advanced cancer patients and controls."
Helicobacter pylori in tumor tissues of patients with advanced
gastric adenocarcinoma: high prevalence but failure to detect
integration. JT Wang, CT Sung, JT Lin, TH Wang. Zhonghua Min Guo Wei
Sheng Wu Ji Mian Yi Xue Za Zhi 1996 Aug;29(3):134-142. In 32 patients
with gastric adenocarcinoma, "For serum antibody, eighteen (56%) of
these patients were positive by ELISA while 24 (75%) were positive by
Western blot. For tissue H. pylori genome, 14 were positive by
histology while 28 (87%) were positive by PCR."
Risk for gastric cancer in people with CagA positive or CagA
negative Helicobacter pylori infection. J Parsonnet, GD Friedman, N
Orentreich, H Vogelman. Gut 1997 Mar;40(3):297-301. Among 90 cases and
89 controls, all HP-infected, versus 63 uninfected [?] controls,
including 13 gastric cancer patients, "Subjects infected with H pylori
who had CagA antibodies were 5.8-fold more likely than uninfected
subjects to develop gastric cancer (95% confidence interval (95% CI) =
2.6-13.0). This was true for both intestinal (odds ratio (OR) 5.1, 95%
CI = 2.1-12.2) and diffuse type (OR 10.1, 95% CI = 2.2-47.4) cancers.
By contrast, H pylori infected subjects without CagA antibodies were
only slightly, and not significantly, at increased risk for cancer (OR
2.2, 95% CI = 0.9-5.4) and any possible association was restricted to
diffuse type carcinoma (OR 9.0, 95% CI = 1.2-65.8)... Educational
attainment, cigarette smoking, and ABO blood group were not associated
Association between Helicobacter pylori and gastric carcinoma in the
city of Malmo, Sweden. A prospective study. JH Siman, A Forsgren, G
Berglund, CH Floren. Scand J Gastroenterol 1997 Dec;32(12):1215-1221.
56 cases of gastric adenocarcinoma and 224 matched controls from a
cohort of 32,906 residents recruited from 1974 through 1992. "The
overall seropositivity prevalence in gastric cancer cases was 82%,
compared with 49% in controls, giving an odds ratio (OR) of 5.0 (95%
confidence interval (CI), 2.2-11.5)... Tumours of the cardia were not
associated with H. pylori (OR, 0.92; 95% CI, 0.23-3.7), which is in
contrast to tumours of the fundus, corpus, and antrum, which were
significantly associated (OR, 11.1; 95% CI, 2.4-71.8)."
Helicobacter pylori infection and gastric neoplasia: correlations
with histological gastritis and tumor histology. K Komoto, K Haruma, T
Kamada, S Tanaka, M Yoshihara, K Sumii, G Kajiyama, NJ Talley. Am J
Gastroenterol 1998 Aug;93(8):1271-1276. "105 patients with gastric
carcinoma, 36 patients with gastric adenoma, and 105 age- and
sex-matched control subjects were examined for H. pylori infection and
histological gastritis. H. pylori status was evaluated by Giemsa
staining and IgG serology... H. pylori seroprevalence was higher in
patients with gastric carcinoma (98 of 105, 93%) and adenoma (34 of 36,
94%) than in control subjects (82 of 105, 71%, p < 0.05). H. pylori
was more prevalent in patients with noncardia (OR, 5.67; 95% CI,
2.25-14.44) than cardia (OR, 5.20; 95% CI, 0.65-41.68) tumors.
Histologic types and tumor stage (early; OR, 6.60; 95% CI, 2.23-19.69,
advanced; OR, 4.27; 95% CI, 1.21-15.03) showed no difference in H.
pylori prevalence." A supposed smoking risk of 3.05 (95% CI, 1.58-5.93).
Helicobacter pylori infection and risk of cardia cancer and
non-cardia gastric cancer. A nested case-control study. S Hansen, KK
Melby, S Aase, E Jellum, SE Vollset. Scand J Gastroenterol 1999
Apr;34(4):353-360. 208 gastric adenocarcinoma cases among 101,601
subjects whose serum was collected between 1972 and 1986 in the
Norwegian JANUS study: H. pylori infection and non-cardia gastric
cancer (odds ratio (OR), 5.15; 95% confidence interval (CI), 2.83-9.37).
Helicobacter pylori infection on the risk of stomach cancer and
chronic atrophic gastritis. ZF Zhang, RC Kurtz, DS Klimstra, GP Yu, M
Sun, S Harlap, JR Marshall. Cancer Detect Prev 1999;23(5):357-367.
"This study included 134 patients with adenocarcinoma of the stomach
(ACS), 67 patients with chronic atrophic gastritis (CAG), and 65 normal
controls recruited at Memorial Sloan-Kettering Cancer Center... H.
pylori infection was diagnosed by pathological evaluation... The odds
ratio (OR) associated with H. pylori infection was 10.4 [95% confidence
interval (CI): 2.6-41.6] for CAG and 11.2 (95% CI: 2.5-50.3) for
gastric cancer in comparison with normal controls, with adjustment for
pack-years of smoking, alcohol drinking, body mass index, total caloric
intake, dietary fat and fiber intake, and Barrett's esophagus."
Helicobacter pylori infection and risk of gastric cancer in
Shanghai, China: updated results based upon a locally developed and
validated assay and further follow-up of the cohort. JM Yuan, MC Yu, WW
Xu, M Cockburn, YT Gao, RK Ross. Cancer Epidemiol Biomarkers Prev 1999
Jul;8(7):621-624. Their previous study failed to show an association
between H. pylori and gastric cancer; "That previous study had a
relatively short time period of follow-up and the enzyme-linked
immunosorbent assay (ELISA) used was based on strains found in Southern
England and without validation among the Chinese... An ELISA developed
and validated among Shanghai residents was used in the present study to
reexamine specific antibodies to H. pylori in 188 gastric cancer
patients and 548 control subjects... Using this alternative assay,
combined with increased follow-up, our latest data contradict our
earlier findings and show a statistically significant association
between H. pylori seropositivity and gastric cancer risk (odds ratio,
1.84; 95% confidence interval, 1.08–3.11). We noted an increasing rate
of seropositivity among cases as the time interval between cohort
enrollment and cancer diagnosis increased. Among subjects followed for
5 or more years after enrollment, the odds ratio for gastric cancer
related to H. pylori seropositivity was 3.74 (95% confidence interval,
Association between infections with CagA-positive or -negative
strains of Helicobacter pylori and risk for gastric cancer in young
adults. Research Group on Prevention of Gastric Carcinoma Among Young
Adults. S Kikuchi, JE Crabtree, D Forman, M Kurosawa. Am J
Gastroenterol 1999 Dec;94(12):3455-3459. In 103 gastric cancer patients
<40 yr of age, 100 inpatients with benign diseases, and 101
screenees younger than age 43 yr: "The overall odds ratios (95%
confidence intervals) for gastric cancer in the H. pylori+/CagA- and
the H. pylori+/CagA+ groups were 15.0 (6.4, 35.2) and 14.6 (6.7, 31.9),
respectively. Between these two groups, no significant difference was
observed in risks for intestinal-type, diffuse-type, early, advanced,
proximal, or distal gastric cancer."
Assessment of gastric carcinoma risk associated with Helicobacter
pylori may vary depending on the antigen used: CagA specific
enzyme-linked immunoadsorbent assay (ELISA) versus commercially
available H. pylori ELISAs. S Maeda, H Yoshida, K Ogura, Y Yamaji, T
Ikenoue, T Mitsushima, H Tagawa, R Kawaguchi, K Mori, K Mafune, T
Kawabe, Y Shiratori, M Omata. Cancer 2000 Apr 1;88(7):1530-1535.
"Anti-CagA seropositivity differed significantly between gastric
carcinoma patients and controls (92.5% vs. 55.0%; P = 0. 0001), showing
an odds ratio of 10.4 (95% confidence interval [CI]: 4.23-29.74). The
difference was less prominent for the seropositivity of HEL-p (77.5%
vs. 58.8%; P = 0.0139; odds ratio: 2. 38; 95% CI: 1.20-4.82) and
insignificant for that of HM-CAP (65.0% vs. 57.5%; P = 0.4325; odds
ratio: 1.30; 95% CI: 0.68-2.49). CONCLUSIONS: The current study
revealed that the antibody assay system used could be one important
factor in the assessment of gastric carcinoma risk for patients with H.
Gastric cancer and Helicobacter pylori: a combined analysis of 12
case control studies nested within prospective cohorts. Helicobacter
and Cancer Collaborative Group. Gut 2001 Sep;49(3):347-353. "Twelve
studies with 1228 gastric cancer cases were considered. The association
with H pylori was restricted to non-cardia cancers (OR 3.0; 95% CI
2.3-3.8) and was stronger when blood samples for H pylori serology were
collected 10+ years before cancer diagnosis (5.9; 3.4-10.3). H pylori
infection was not associated with an altered overall risk of cardia
cancer (1.0; 0.7-1.4). CONCLUSIONS: These results suggest that 5.9 is
the best estimate of the relative risk of non-cardia cancer associated
with H pylori infection and that H pylori does not increase the risk of
cardia cancer. They also support the
idea that when H pylori status is
assessed close to cancer diagnosis, the magnitude of the non-cardia
association may be underestimated [emphasis added]." "Assuming
an average prevalence of
H pylori of 35% in developed countries and 85% in developing countries,
an OR of 5.9 suggests that between about 65% and 80%, respectively, of
non-cardia gastric cancers are attributable to H pylori infection and
therefore potentially preventable by control of the infection."
Helicobacter pylori in gastric cancer established by CagA immunoblot as a marker of past infection. AM Ekstrom, M Held, LE Hansson, L Engstrand, O Nyren. Gastroenterology 2001 Oct;121(4):784-791. HP infection may disappear spontaneously during progression to gastric cancer, so antibodies that persist longer after eradication were used. "RESULTS: Using IgG ELISA only, the adjusted OR for noncardia gastric cancer among H. pylori-positive subjects was 2.2 (95% confidence interval [CI], 1.4-3.6). When ELISA-/CagA+ subjects (odds ratio [OR], 68.0) were removed from the reference, the OR rose to 21.0 (95% CI, 8.3-53.4) and the previous effect modification by age disappeared. ELISA+/CagA- subjects had an OR of 5.0 (95% CI, 1.1-23.6). There were no associations with cardia cancer. CONCLUSIONS: The weaker H. pylori-cancer relationships in studies based on IgG ELISA rather than CagA may be caused by misclassification of relevant exposure. A much stronger relationship emerges with more accurate exposure classification. In the general Swedish population, 71% of noncardia adenocarcinomas were attributable to H. pylori."Ekstrom - Gastroenterology 2001 abstract / PubMed
Helicobacter pylori CagA seropositivity and gastric carcinoma risk
in a Japanese American population. AM Nomura, J Lee, GN Stemmermann, RY
Nomura, GI Perez-Perez, MJ Blaser. J Infect Dis 2002 Oct
15;186(8):1138-1144. 261 incident cases of gastric carcinoma of the
distal stomach among 9963 Japanese American men recruited between 1967
and 1977: "Compared with H. pylori-negative, CagA-negative men, H.
pylori-positive, CagA-negative men had an odds ratio (OR) of 2.7 (95%
confidence interval [CI], 1.3-5.6) for intestinal gastric carcinoma.
Men seropositive for both H. pylori and CagA had an OR of 4.1 (95% CI,
Serum Helicobacter pylori IgG and IgA levels in patients with
gastric cancer. C Atalay, G Atalay, M Altinok. Neoplasma
2003;50(3):185-190. "Serological tests revealed IgA and IgG positivity
as 53.9% and 50.9%, respectively, while 74.5% had positive results for
either IgA or IgG. Serum IgA positivity was significantly higher in
gastric cancer group compared to control group (p=0.02). In contrast,
serum IgG positivity did not show a significant difference in both
groups and either IgG or IgA seropositivity was significantly higher in
patients with gastric cancer compared to control patients (p=0.04).
This study revealed a higher seroprevalence of Helicobacter pylori in
gastric cancer patients and IgA was a better predictor of
pylori seropositivity in gastric cancer patients"
Is Helicobacter pylori infection a necessary condition for noncardia
gastric cancer? H Brenner, V Arndt, C Stegmaier, H Ziegler, D
Rothenbacher. Am J Epidemiol 2004 Feb 1;159(3):252-258. "Although the
association between Helicobacter pylori infection and gastric cancer is
well established, this association might have been underestimated in
epidemiologic studies because of possible clearance of the infection in
the course of disease development [emphasis added]. The authors
hypothesis in a case-control study from Saarland, Germany (68 cases
first diagnosed between 1996 and 1998 and 360 controls), with serologic
assessment of H. pylori infection in which various exclusion criteria
were used to minimize potential bias from this source. Joint
application of three such exclusion criteria (blood sample taken more
than 90 days after gastrectomy, advanced (T4) gastric cancer, and CagA
positivity in Western blot analysis despite a negative result in
anti-H. pylori immunoglobulin G enzyme-linked immunosorbent assay)
increased the odds ratio of noncardia gastric cancer from 3.7 (95%
confidence interval (CI): 1.7, 7.9) to 18.3 (95% CI: 2.4, 136.7) for
any H. pylori infection and from 5.7 (95% CI: 2.6, 12.8) to 28.4 (95%
CI: 3.7, 217.1) for CagA-positive H. pylori infections. Furthermore,
there was no single H. pylori-negative patient out of 32 patients with
noncardia gastric cancer left after additional exclusion of subjects
with borderline levels in immunoglobulin G enzyme-linked immunosorbent
assay. The H. pylori-gastric cancer relation may be much stronger than
previously thought, and H. pylori infection may even be a (close to)
necessary condition for development of noncardia gastric cancer."
Is the association between Helicobacter pylori and gastric cancer
confined to CagA-positive strains? M Held, L Engstrand, LE Hansson, R
Bergstrom, T Wadstrom, O Nyren. Helicobacter 2004 Jun;9(3):271-277.
"100 case patients with a newly diagnosed gastric adenocarcinoma and 96
control patients with diseases unrelated to H. pylori status.
Antibodies to H. pylori were analyzed by enzyme-linked immunosorbent
assay (ELISA), and antibodies to CagA were detected by immunoblot...
ELISA positivity was associated with an increased risk of gastric
adenocarcinoma compared to ELISA negativity (OR for gastric cancer
regardless of site 3.9, 95% CI 1.9-8.2). The OR was 7.4 (95% CI
3.3-16.6) for CagA-positive relative to CagA-negative subjects. Among
ELISA-positive subjects the presence of CagA antibodies increased the
risk 3.6 times (95% CI 1.2-11.1). ELISA-positive CagA-negative
infections were associated with a fourfold increased risk (OR = 4.2,
95% CI 1.0-17.0) compared to no infection (ELISA-negative and
Association of Helicobacter pylori infection and environmental
factors in non-cardia gastric cancer in Japan. A Machida-Montani, S
Sasazuki, M Inoue, S Natsukawa, K Shaura, Y Koizumi, Y Kasuga, T
Hanaoka, S Tsugane. Gastric Cancer 2004;7(1):46-53. "H. pylori
infection was strongly associated with non-cardia gastric cancer after
adjustment for possible confounding factors (odds ratio [OR], 8.2; 95%
confidence interval [CI], 3.7-18.2)." They claim an OR of 2.8 for
smoking, which is likely due to false HP-negatives, because the cases
were newly diagnosed.
Relationship between Helicobacter pylori infection and the
prevalence, site and histological type of gastric cancer. M Kato, M
Asaka, Y Shimizu, A Nobuta, H Takeda, T Sugiyama; Multi-Centre Study
Group. Aliment Pharmacol Ther 2004 Jul;20 Suppl 1:85-89. "The
prevalence of H. pylori infection in gastric cancer patients was
markedly high in all age groups. In contrast, the rate increased with
age among control subjects. The overall prevalence of H. pylori
infection in control subjects was 50.2% (3300/6578) vs. 82.8% in
gastric cancer patients (2072/2503) (OR = 2.47; 95% CI: 2.19-2.79). The
prevalence of H. pylori in early gastric cancer was significantly
higher than that in advanced gastric cancer (86.5% vs. 75.7%; OR =
2.06; 95% CI: 1.66-2.55)."
Association of Helicobacter pylori IgA antibodies with the risk of
peptic ulcer disease and gastric cancer. TU Kosunen, K Seppala, S
Sarna, A Aromaa, P Knekt, J Virtamo, A Salomaa-Rasanen, H Rautelin.
World J Gastroenterol 2005 Nov 21;11(43):6871-6874. Versus controls
with chronic gastritis, IgA antibodies to H. pylori were more strongly
associated with gastric cancer and gastric ulcers than were IgG
antibodies. "Severe atrophic gastritis
may progress to a disease stage
when Helicobacters first gradually decrease in number, then disappear
and finally also Helicobacter antibodies, the longest lasting
indicators of the infection, fall to a normal level. In particular, in
elderly subjects with non-cardia cancer, there may be several
individuals who at the time of diagnosis may have lost all direct
indicators of their burnt out Helicobacter infection" [emphasis
Effect of Helicobacter pylori infection combined with CagA and
pepsinogen status on gastric cancer development among Japanese men and
women: a nested case-control study. S Sasazuki, M Inoue, M Iwasaki, T
Otani, S Yamamoto, S Ikeda, T Hanaoka, S Tsugane; Japan Public Health
Center Study Group. Cancer Epidemiol Biomarkers Prev 2006
Jul;15(7):1341-1347. 511 gastric cancer cases matched to 511 controls
from a cohort of 123,576. "The adjusted odds ratio (95% confidence
interval) of gastric cancer associated with H. pylori infection was 5.1
(3.2-8.0). Assuming all CagA-positive subjects are true H. pylori
positives doubled this risk. Atrophic gastritis was also associated
with an elevated risk of gastric cancer and the risk increased further
with pepsinogen levels."
Serum antibody positivity for distinct Helicobacter pylori antigens
in benign and malignant gastroduodenal disease. C Schumann, K
Triantafilou, FM Rasche, A Möricke, K Vogt, M Triantafilou, P
Hahn, EM Schneider, PM Lepper. Int J Med Microbiol 2006
Aug;296(4-5):223-228. "Serum samples were taken from 285 patients who
underwent gastroscopy. H. pylori infection was diagnosed by histology,
culture or rapid urease test (RUT). Serum IgG reactivity against H.
pylori-specific antigens was studied by Western blot. There was a
significant association between the diagnosis of gastric cancer and the
presence of IgG antibodies against the 19.5, 33 and 136 kDa (CagA)
antigens. Comparing all H. pylori-positive patients with the gastric
cancer group for the presence of the 19.5, 33 and 136 kDa (CagA)
antigens, the results were as follows: chi2: 17.482, p < 0.001,
power P = 0.994, odds ratio (OR) for the presence of gastric cancer:
19.5 (95% confidence interval (CI): 4.11-92.56). Antibodies against
CagA alone or other bands (except 33 and 19.5 kDa antigens), as well as
the age of patients were not related to a diagnosis of gastric cancer."
Age and severity of mucosal lesions influence the performance of
serologic markers in Helicobacter pylori-associated gastroduodenal
pathologies. M Camorlinga-Ponce, L Flores-Luna, E Lazcano-Ponce, R
Herrero, F Bernal-Sahagún, JM Abdo-Francis, J
Aguirre-García, N Muñoz, J Torres. Cancer Epidemiol
Biomarkers Prev 2008 Sep;17(9):2498-2504. 368 patients with
non–atrophic gastritis, 126 with precancerous lesions, 65 with gastric
cancer, and 59 with duodenal ulcer. "Detection of infection and IgG
against CagA had a significant increase from non–atrophic gastritis to
mild and up to advanced stages of metaplasia (P < 0.05), followed by
decreased infection and IgG to CagA in patients with gastric cancer (P
< 0.05). However, infection and CagA antibodies were associated with
young gastric cancer cases. Duodenal ulcer showed a significant
association with infection detected by histology and serology,
particularly among women, and a trend to associate with IgG to CagA." "H. pylori is able to colonize only
normal gastric epithelia and when it is altered because of mucosal
damage, such as during the appearance of preneoplastic lesions, the
infection tends to disappear. Fading of the infection would alter
diagnostic tests, and those documenting active infection such as
culture or histology become negative, whereas those testing the memory
of infection, such as humoral immune response, decline more gradually."
Factors contributing to the underestimation of Helicobacter
pylori-associated gastric cancer risk in a high-prevalence population.
B Peleteiro, N Lunet, R Barros, C La Vecchia, H Barros. Cancer Causes
Control 2010 Aug;21(8):1257-1264. 420 non-cardia gastric cancer
patients and 1389 population controls. "When assessing infection by
ELISA, the OR for its association with gastric cancer decreases and
reverts as IgG titers increased, from 1.96 (95% CI: 1.09-3.54) for
borderline positive results (16.0-21.9 RU/ml) to 0.52 (95% CI:
0.36-0.74) for the highest IgG levels (> or = 102.0 RU/ml)... The
presence of CagA (Western Blot) was associated with an increased risk
of gastric cancer (OR = 11.32; 95% CI: 5.64-22.73). CONCLUSION: The use
of methods with low sensitivity to detect past infection leads to a
substantial underestimation of gastric cancer risk in high-prevalence
A CagA-independent cluster of antigens related to the risk of non-cardia gastric cancer: Associations between helicobacter pylori antibodies and gastric adenocarcinoma explored by multiplex serology. H Song, A Michel, O Nyrén, AM Ekström, M Pawlita, W Ye. Int J Cancer 2014 Jun 15;134(12):2942-2950. Point estimates for all antibodies were above unity, 15 significant with top three being CagA (OR=9.2), GroEL (6.6), HyuA (3.6). ORs were substantially attenuated in individuals with chronic atrophic gastritis. Principal component analysis identified two significant factors: a CagA-dominant factor (antibodies against CagA, VacA, and Omp as prominent markers), and a non-CagA factor (antibodies against NapA and Catalase as prominent markers). Both factors showed dose-dependent associations with non-cardia GAC risk (CagA-dominant factor, highest vs. lowest quartiles, OR=16.2 [95% CI 4.8-54.9]; non-CagA factor OR=5.3 [95%CI 2.1-13.3])."Song - Int J Cancer 2014 abstract / PubMed
virus is also involved in gastric carcinoma.]
Helicobacter pylori infection and gastric lymphoma. J Parsonnet, S
Hansen, L Rodriguez, AB Gelb, RA Warnke, E Jellum, N Orentreich, JH
Vogelman, GD Friedman. N Engl J Med 1994 May 5;330(18):1267-1271. 33
patients with gastric non-Hodgkin's lymphoma, 31 patients with
nongastric non-Hodgkin's lymphoma, 132 controls. For gastric NHL and
previous H. pylori infection: matched odds ratio, 6.3; 95 percent
confidence interval, 2.0 to 19.9.
A comparison of Helicobacter pylori and H. heilmannii gastritis. A
matched control study involving 404 patients. M Stolte, G Kroher, A
Meining, A Morgner, E Bayerdorffer, B Bethke. Scand J Gastroenterol
1997 Jan;32(1):28-33. 202 patients with H. heilmannii gastritis and 202
matched control patients with H. pylori gastritis and duodenal ulcer.
"In a single case of H. heilmannii gastritis a concurrent gastric
carcinoma and in seven cases a low-grade gastric MALT lymphoma were
found... Whether the observed relatively frequent association of H.
heilmannii infection and gastric MALT lymphoma is coincidental, and
whether H. heilmannii gastritis is more commonly associated with MALT
lymphoma than is H. pylori gastritis must be investigated in further
Blood groups Lewis(b) and ABH expression in gastric mucosa: lack of
inter-relation with Helicobacter pylori colonisation and occurrence of
gastric MALT lymphoma. G Oberhuber, A Kranz, C Dejaco, B Dragosics, I
Mosberger, W Mayr, T Radaszkiewicz. Gut 1997 Jul;41(1):37-42.
"Colonisation with H pylori was found in 134 (72·8%) patients,
including 55 (61·1%) of MALT lymphoma negative and 79 (84%) of
MALT lymphoma positive cases. In two cases H pylori status remained
unclear. The occurrence of MALT lymphomas was highly significantly
associated with H pylori colonisation (p<0·0003)."
Helicobacter pylori and non-Helicobacter pylori bacterial flora in
gastric mucosal and tumour specimens of patients with primary gastric
lymphoma. D Jonkers, I Gisbertz, A de Bruine, F Bot, JW Arends, E
Stobberingh, H Schouten, R Stockbrugger. Eur J Clin Invest 1997
Nov;27(11):885-892. "In total, 32 (61.5%) patients were H. pylori
positive using IMM [specific immunohistochemical stain for H. pylori]
and 34 (65.4%) were non-H. pylori positive using MG [modified Giemsa
stain]. In 24 out of the 34 patients, the non-H. pylori flora consisted
mainly of cocci in combination with rods in 15 patients, mostly in
minor quantities; in another 10 patients, high numbers of both cocci
and different types of rods were present. Most non-H. pylori bacteria
were localized superficially, although in 22 patients minor quantities
of non-H. pylori were also seen in the glandular lumina."
Hematopoietic cancer and peptic ulcer: a multicenter case-control
study. P Vineis, P Crosignani, C Sacerdote, A Fontana, G Masala, L
Miligi, O Nanni, V Ramazzotti, S Rodella, E Stagnaro, R Tumino, C
Vigano, C Vindigni, AS Costantini. Carcinogenesis 1999
Aug;20(8):1459-1463. 2671 cases and 1718 controls. "Subjects who
reported a diagnosis of peptic ulcer had a relative risk of 5.6 [95%
confidence interval (CI) 3.8–8.0] for gastric NHL, whereas the estimate
for non-gastric NHL was 1.3 (1.0–1.6)... We found a strong effect
modification by educational level, with ORs for ulcer more elevated in
higher social groups. Gender was an effect modifier (OR = 4.1 in males,
9.2 in females; P = 0.03 for heterogeneity)... Almost all gastric
lymphomas were B-cell NHLs of intermediate grade according to the
working formulation; the majority belonged to the mucosa-associated
lymphoid tissue (MALT) type." Non-Hodgkin's lymphomas have been
increasing by 3-4% a year in Western countries.
Helicobacter pylori and gastric lymphoma: high seroprevalence of CagA in diffuse large B-cell lymphoma but not in low-grade lymphoma of mucosa-associated lymphoid tissue type. JC Delchier, D Lamarque, M Levy, EM Tkoub, C Copie-Bergman, L Deforges, MT Chaumette, C Haioun. Am J Gastroenterol 2001 Aug;96(8):2324-2328. 45/53 (85%) gastric lymphoma patients were positive for H. pylori (78% (29/37) in LGLM and 100% (16/16) in DLBCL).Delchier - Am J Gastroenterol 2001 abstract / PubMed
Helicobacter pylori and malignant lymphoma in Spain. S de Sanjose, A
Dickie, T Alvaro, V Romagosa, M Garcia Villanueva, E Domingo-Domenech,
A Fernandez de Sevilla, E El-Omar. Cancer Epidemiol Biomarkers Prev
2004 Jun;13(6):944-948. 536 cases. "H. pylori infection was not
associated with an overall increased risk of lymphoma. Within all
lymphoma categories, H. pylori was associated with an almost 4-fold
increased risk of splenic MZL (OR = 3.97, 95% CI = 0.92-17.16, P value
= 0.065). Of 26 patients with splenic MZL, 24 had detectable antibodies
against H. pylori... H. pylori was not associated with an overall
increased risk of extranodal lymphomas (OR = 0.73, 95% CI = 0.44-1.22).
However, when specific sites were explored, all 10 lymphomas localized
primarily in the stomach were H. pylori seropositive. No other lymphoma
category shown in Table 3 showed an association with H. pylori." HP
infection was not related to smoking.
A past history of gastric ulcers and Helicobacter pylori infection
increase the risk of gastric malignant lymphoma. T. Suzuki, K Matsuo, H
Ito, K Hirose, K Wakai, T Saito, S Sato, Y Morishima, S Nakamura, R
Ueda, K Tajima. Carcinogenesis 2006 Jul;27(7):1391-1397. 645 cases,
3445 controls. "An association with a history of gastric, but not
duodenal ulcers was found for gastric lymphoma [odds ratio (OR) = 5.41,
95% confidence interval (CI): 3.12-9.39]. In the examination according
to histological subtype, the OR was high for both gastric
mucous-associated lymphoid tissue (MALT) lymphoma (OR = 5.54, 95% CI:
2.56-12.01) and diffuse large B-cell lymphoma (DLBCL) (OR = 7.23, 95%
CI: 2.62-19.90). In the analysis of H. pylori antibody, the risk of
total gastric lymphoma was associated with H. pylori infection (OR =
5.34, 95% CI: 1.42-20.05). A high prevalence of H. pylori infection was
also found for both gastric MALT lymphoma (8 out of 10: 80.0%) and
DLBCL (8 out of 9: 88.9%)."
Helicobacter pylori infection and the risk of gastric malignancy. PI
Hsu, KH Lai, PN Hsu, GH Lo, HC Yu, WC Chen, FW Tsay, HC Lin, HH Tseng,
LP Ger, HC Chen. Am J Gastroenterol 2007 Apr;102(4):725-730. 1,225
patients with nonulcer dyspepsia, gastric ulcers, or duodenal ulcers.
"During a mean follow-up of 6.3 yr, gastric adenocarcinoma developed in
7 of the 618 H. pylori-infected patients, but in none of the 607
uninfected patients (1.1%vs 0.0%, P= 0.015). The incidence of gastric
lymphoma was 0.2% (1/618) and 0% in H. pylori-infected and uninfected
patients. Taken together, the development rate of gastric malignancy in
H. pylori-infected patients was significantly higher than that in
uninfected patients (1.3%vs 0%, P= 0.007). Among H. pylori-infected
subjects, the incidence of gastric malignancy was similar between those
receiving and not receiving eradication therapy (1.4%vs 1.2%).
Multivariate analysis showed that intestinal metaplasia was the only
independent factor predicting subsequent development of gastric
malignancy in H. pylori-infected subjects with an odds ratio of 4.5
(95% CI 1.1-19.1)."
The association between conjunctival MALT lymphoma and Helicobacter
pylori. SB Lee, JW Yang, CS Kim. Br J Ophthalmol 2008
Apr;92(4):534-536. "H pylori DNA was identified in all 15 specimens of
conjunctival MALT lymphomas and none of the controls. Of these 15 H
pylori positive lymphoma specimens, the vacA s1 and vacA m2 alleles
were detected in two, and only vacA s1 allele was detected in 11."
Primary low-grade and high-grade gastric MALT-lymphoma presentation.
A Zullo, C Hassan, A Andriani, F Cristofari, V Cardinale, GP Spinelli,
S Tomao, S Morini. J Clin Gastroenterol 2010 May-Jun;44(5):340-344.
Review of 2000 patients. "Helicobacter pylori infection was present in
88.8% of considered patients. At endoscopy, the ulcerative type was the
most frequent presentation, although low-grade lymphoma was diagnosed
on normal/hyperemic gastric mucosa in 9% of cases. Patients with
high-grade lymphoma presented alarm symptoms (anemia and/or melena
and/or hemorrhage, persistent vomiting, weight loss), an exophytic or
ulcerative lesion, a stage III-IV, and a H. pylori negative status more
frequently than low-grade lymphoma cases."
Repeating gastric biopsy for accuracy of gastric lymphoma diagnosis.
W Xu, C Zhou, G Zhang, H Wang, L Wang, J Guo. Gastroenterol Nurs 2010
Jul-Aug;33(4):313-317. 70.4% of 54 cases of gastric lymphoma were
positive for H. pylori. "Of these, 13 cases were diffuse large B-cell
lymphoma and 41 cases were marginal zone B-cell lymphoma."
Ocular adnexal lymphoma and Helicobacter pylori gastric infection. D
Decaudin, A Ferroni, A Vincent-Salomon, K Beldjord, P Validire, P de
Cremoux, P Validire, C Plancher, C Mathiot, E Macintyre, B Asselain, J
Girodet, F Mal, N Brousse, JL Beretti, R Dendale, L Lumbroso-Le Rouic,
O Hermine, M Lecuit. Am J Hematol 2010 Sep;85(9):645-649. 83 patients
with OAL, 101 with extraophthalmologic extragastric lymphoma, and 156
controls. "We found gastric Hp infection in 37 OAL patients (45%), in
25 extraophthalmologic extragastric lymphoma cases (25%), and in 18
controls individuals (12%) (P < 0.0001 OAL/C and P < 0.01
OAL/extra-OAL cases)... Gastric Hp infection only correlated with
MALT/LPL lymphoma (P = 0.03). There is a significant association
between gastric Hp infection and MALT/LPL OAL."
Helicobacter pylori and gastric mucosa-associated lymphoid tissue lymphoma: Recent progress in pathogenesis and management. S Nakamura, T Matsumoto. World J Gastroenterol 2013 Dec 7;19(45):8181-8187. Review. In approximately 90% of cases, Helicobacter pylori (H. pylori) infection plays the causative role in the pathogenesis, and H. pylori eradication is nowadays the first-line treatment for this disease, which leads to complete disease remission in 50%-90% of cases. In H. pylori-dependent cases, microbe-generated immune responses, including interaction between B and T cells involving CD40 and CD40L co-stimulatory molecules, are considered to induce the development of MALT lymphoma. In H. pylori-independent cases, activation of the nuclear factor-κB pathway by oncogenic products of specific chromosomal translocations such as t(11;18)/API2-MALT1, or inactivation of tumor necrosis factor alpha-induced protein 3 (A20) are considered to contribute to the lymphomagenesis."Nakamura - World J Gastroenterol 2013 full article / PubMed
[Treatment of low-grade gastric MALT lymphoma with Helicobacter
pylori eradication. Follow-up of the histological and molecular
response]. C Montalban, A Manzanal, D Boixeda, C Redondo, I Alvarez, B
Frutos, JL Calleja, P Sanchez-Godoy, C Bellas. Med Clin (Barc) 1998 Jan
24;110(2):41-44. After HP eradication, lymphomas regressed in 10/11
patients. Nine were still in remission 18 months later.
Treatment of low grade gastric mucosa-associated lymphoid tissue
lymphoma in stage I with Helicobacter pylori eradication. Long-term
results after sequential histologic and molecular follow-up. C
Montalban, A Santon, D Boixeda, C Redondo, I Alvarez, JL Calleja, CM de
Argila, C Bellas. Haematologica 2001 Jun;86(6):609-617. Regression in
18 of 19 consecutive patients with stage I gastric low grade MALT
lymphoma; 15 remaining patients are still in histologic remission after
a mean period of 43 months.
Changes in pattern of immunoglobulin heavy chain gene rearrangement
and MIB-1 staining before and after eradication of Helicobacter pylori
in gastric mucosa-associated lymphoid tissue (MALT) lymphoma. M Kanda,
J Suzumiya, K Ohshima, M Okada, K Tamura, M Kikuchi. Leuk Lymphoma 2001
Aug;42(4):639-647. 9/12 gastric MALT lymphomas regressed completely
after HP eradication.
Regression of low-grade gastric mucosa-associated lymphoid tissue
lymphoma after eradication of Helicobacter pylori: possible association
with p16 hypermethylation. YS Kim, JS Kim, HC Jung, CH Lee, CW Kim, IS
Song, CY Kim. J Gastroenterol 2002 Jan;37(1):17-22. "Eighteen patients
(90%) achieved complete remission, with a median duration of 15.7
months. The initial detection rate of p16 hypermethylation was 58% (7
of the 12 patients in whom p16 hypermethylation was evaluated
successfully). In a serial investigation, 3 patients who were
followed-up for a median 28 months showed that the p16 hypermethylation
Long-term persistence of molecular disease after histological
remission in low-grade gastric MALT lymphoma treated with H. pylori
eradication. Lack of association with translocation t(11;18): a 10-year
updated follow-up of a prospective study. C Montalban, S Santon,
C Redondo, M Garcia-Cosio, D Boixeda, E Vazquez-Sequeiros, F Norman, CM
de Argila, I Alvarez, V Abraira, C Bellas. Ann Oncol 2005
Sep;16(9):1539-1544. "Twenty-two of the 24 patients (91%) achieved
disappearance of the lymphoma. Eighteen (82%) of the 22 histologically
cured patients and 16 of the 19 (84%) with long follow-up had
monoclonality," but "Only one patient (6%) with persistent
HLA-DQA1*0103-DQB1*0601 haplotype and Helicobacter pylori-positive
gastric mucosa-associated lymphoid tissue lymphoma. Y Kawahara, M
Mizuno, T Yoshino, K Yokota, K Oguma, H Okada, S Fujiki, Y Shiratori.
Clin Gastroenterol Hepatol 2005 Sep;3(9):865-868. "After H pylori
eradication, the lymphomas regressed completely in all 10 patients who
possessed the DQA1*0103-DQB1*0601 haplotype but in only 4 of the 8
without this haplotype (P = .023)."
Long-term results of anti-Helicobacter pylori therapy in early-stage gastric high-grade transformed MALT lymphoma. LT Chen, JT Lin, JJ Tai, GH Chen, HZ Yeh, SS Yang, HP Wang, SH Kuo, BS Sheu, CM Jan, WM Wang, TE Wang, CW Wu, CL Chen, IJ Su, J Whang-Peng, AL Cheng. J Natl Cancer Inst 2005 Sep 21;97(18):1345-1353. "H. pylori was eradicated in 97% (30 of 31) of evaluable H. pylori-positive low-grade patients and in 92% (22 of 24) of high-grade patients, which led to CR in 80% (24 of 30, 95% confidence interval [CI] = 65% to 95%) and 64% (14 of 22, 95% CI = 42% to 86%) of patients, respectively. None of the five patients who were either initially H. pylori negative or had persistent H. pylori infection after antibiotics achieved CR. After median follow-up of more than 5 years in complete responders, tumor recurrence was observed in three (13%) low-grade patients but not in high-grade patients."Chen - J Natl Cancer Inst 2005 abstract / PubMed
Comparison of localized gastric mucosa-associated lymphoid tissue
(MALT) lymphoma with and without Helicobacter pylori infection. T
Akamatsu, T Mochizuki, Y Okiyama, A Matsumoto, H Miyabayashi, H Ota.
Helicobacter 2006 Apr;11(2):86-95. "Complete regression was achieved
with antibiotic therapy against H. pylori-negative gastric MALT
lymphoma in one of nine patients (11.1%), compared to 28 of 38 patients
(73.7%) with H. pylori-positive gastric MALT lymphoma (p < .001)...
Two of 16 patients (12.5%) with H. pylori-negative gastric MALT
lymphoma died because of the transformation of the disease into diffuse
large B-cell lymphoma."
Successful antibiotic treatment of Helicobacter pylori negative
gastric mucosa associated lymphoid tissue lymphomas. M Raderer, B
Streubel, S Wohrer, M Hafner, A Chott. Gut 2006 May;55(5):616-618. In
six patients with MALT lymphoma of the stomach, "H pylori infection was
ruled out by histology, urease breath test, serology, and stool antigen
testing." After antibiotic treatment, lymphomas regressed completely in
four patients and partially in one.
Gastric MALT lymphoma: epidemiology and high adenocarcinoma risk in
a nation-wide study. LG Capelle, AC de Vries, CW Looman, MK Casparie, H
Boot, GA Meijer, EJ Kuipers. Eur J Cancer 2008 Nov;44(16):2470-2476.
"1419 patients were newly diagnosed with gMALT, compatible with an
incidence of 0.41/100,000/year. GC was diagnosed in 34 (2.4%) patients
of the cohort. Patients with gMALT had a sixfold increased risk for GC
in comparison with the general population (p<0.001). This risk was
16.6 times higher in gMALT patients aged between 45 and 59 years than
in the Dutch population (p<0.001)."
Effects of Helicobacter pylori eradication on early stage gastric
mucosa-associated lymphoid tissue lymphoma. A Zullo, C Hassan, F
Cristofari, A Andriani, V De Francesco, E Ierardi, S Tomao, M Stolte, S
Morini, D Vaira. Clin Gastroenterol Hepatol 2010 Feb;8(2):105-110.
Review of 32 studies, with 1408
patients treated only by H pylori
eradication. "The MALT lymphoma remission rate was 77.5% (95%
confidence interval, 75.3-79.7), and was significantly higher in
patients with stage I than stage II(1) lymphoma (78.4% vs 55.6%; P =
.0003) and in Asian than in Western groups (84.1% vs 73.8%; P =
.0001)... In an analysis of data from 994 patients, 7.2% experienced
lymphoma relapse during 3253 patient-years of follow-up evaluation,
with a yearly recurrence rate of 2.2%. Infection and lymphoma were
cured by additional eradication therapy in all patients with H pylori
Decreasing incidence of gastric MALT lymphomas in the era of
anti-Helicobacter pylori interventions: results from a population-based
study on extranodal marginal zone lymphomas. S Luminari, M Cesaretti, L
Marcheselli, I Rashid, S Madrigali, A Maiorana, M Federico. Ann Oncol
2010 Apr;21(4):855-859. 165 cases from the Modena Cancer Registry.
"[T]he incidence of gastric mucosa-associated lymphoid tissue (g-MALT)
lymphomas (N = 51) markedly declined during the study period, dropping
from 1.4 in 1997 to 0.2 in 2002 and then remaining stable until 2007;
the calculated annual percent change for g-MALT was -17.0% (95%
confidence interval -26.6% to -6.2%). We also observed a significant
decrease in the rate of g-MALT associated with Helicobacter pylori (HP)
infection from 61% to 17% of patients diagnosed before and after 2002
(P = 0.007; P for trend = 0.016)."
Gastric MALT lymphoma: old and new insights. A Zullo, C Hassan, L Ridola, A Repici, R Manta, A Andriani. Ann Gastroenterol 2014;27(1):27-33. Review.Zullo - Ann Gastroenterol 2014 full article / PubMed Central
Smoking does not contribute to duodenal ulcer relapse after
Helicobacter pylori eradication. TJ Borody, LL George, S Brandl, P
Andrews, E Jankiewicz, N Ostapowicz. Am J Gastroenterol 1992
Oct;87(10):1390-1393. 80 smokers and 117 nonsmokers: "In the 197
patients with eradicated H. pylori and cured DU, there has been no
recurrence of ulcer, regardless of smoking status. We conclude that in
patients with DU in whom H. pylori infection is eradicated, ulcer
disease does not recur, as observed for up to 6 yr. Furthermore,
cigarette smoking is not a risk factor for DU recurrence, provided H.
pylori is eradicated."
Helicobacter pylori infection, cigarette smoking and alcohol
consumption. A histological and clinical study on 286 subjects. G
Battaglia, F Di Mario, M Pasini, PM Donisi, P Dotto, ME Benvenuti, V
Stracca-Pansa, M Pasquino. Ital J Gastroenterol 1993 Oct;25(8):419-424.
"Hp infection was found to be significantly correlated with presence of
ulcer symptoms, gastritis, lymphoid follicles and, among DU patients,
with active DU. The other parameters considered did not influence Hp
infection. In conclusion smoking habits and alcohol consumption do not
affect Hp infection of the stomach."
Helicobacter pylori infection and the risk for duodenal and gastric
ulceration. A Nomura, GN Stemmermann, PH Chyou, GI Perez-Perez, MJ
Blaser. Ann Intern Med 1994 Jun 15;120(12):977-981. 150 gastric ulcer
and 65 duodenal ulcer patients from Honolulu Heart Program
prospective study. "Ninety-three percent (139 of 150) of the patients
with gastric ulcer and 78% (117 of 150) of the matched controls had a
positive H. pylori-specific IgG antibody level, yielding an odds ratio
of 3.2 (P = 0.001). (The odds ratio is determined by dividing 32
± pairs by 10 -/+ pairs.) Ninety-two percent of the
case-patients with duodenal ulcer and 78% of the matched controls had a
positive test result, yielding an odds ratio of 4.0 (P = 0.03)."
Helicobacter pylori infection, anti-cagA antibodies and peptic
ulcer: a case-control study in Italy. D Palli, M Menegatti, G Masala, C
Ricci, C Saieva, J Holton, L Gatta, M Miglioli, D Vaira. Aliment
Pharmacol Ther 2002 May;16(5):1015-1020. 275 duodenal and 71 gastric
ulcer patient cases, with 1280 non-ulcer dyspepsia controls.
Relation between Helicobacter pylori cagA status and risk of peptic
ulcer disease. AM Nomura, GI Perez-Perez, J Lee, G Stemmermann, MJ
Blaser. Am J Epidemiol 2002 Jun 1;155(11):1054-1059. 229 cases tested
for IgG to H. pylori and CagA. "Persons with H. pylori positivity had
an odds ratio of 4.0 (95% confidence interval (CI): 1.9, 8.5) for
gastric ulcer and 2.5 (95% CI: 0.8, 7.4) for duodenal ulcer. For CagA
positivity, the odds ratios were 1.4 (95% CI: 0.9, 2.4) for gastric
ulcer and 2.6 (95% CI: 1.1, 5.8) for duodenal ulcer. Subjects who were
seropositive for both H. pylori and CagA had an odds ratio of 4.4 (95%
CI: 1.8, 10.5) for gastric ulcer and 5.8 (95% CI: 1.1, 30.0) for
duodenal ulcer." [The study claimed an association with smoking, which
could disappear if IgA positivity was determined as well -cast]
The prevalence of peptic ulcer not related to Helicobacter pylori or
non-steroidal anti-inflammatory drug use is negligible in southern
Europe. MT Arroyo, M Forne, CM de Argila, F Feu, J Arenas, J de la
Vega, V Garrigues, F Mora M Castro, L Bujanda, A Cosme, A Castiella, JP
Gisbert, A Hervas, A Lanas. Helicobacter 2004 Jun;9(3):249-254. "Of the
472 patients who had duodenal ulcers, 95.7% (n = 452) were H.
pylori-positive and only 1.69% (n = 8) were negative for both H. pylori
infection and NSAID use; 193 patients had benign gastric ulcers and 87%
(n = 168) of them were infected by H. pylori (p <.001 vs. duodenal
Helicobacter pylori membrane protein 1: a new carcinogenic factor of
helicobacter pylori. M Suganuma, M Kurusu, S Okabe, N Sueoka, M
Yoshida, Y Wakatsuki, H Fujiki. Cancer Res 2001 Sep 1;61(17):6356-6359.
"Two cell lines, BALB/3T3 cells as control and v-Ha-ras-transfected
BALB/3T3 cells (Bhas 42 cells) as putative initiated cells, were each
transfected with HP-MP1, urease B genes, or vector alone. All of the
Bhas/mpl clones showed strong expression of tumor necrosis factor-α
gene and produced tumors in 100% of nude mice. Two Bhas/ure clones
showed weak tumorigenicity; the other Bhas and BALB clones showed none.
Results indicate strong carcinogenic activity of HP-MP1 in cooperation
with viral Ras protein and weak activity of urease B."
Helicobacter pylori infection affects the expression of PCNA, p53,
c-erbB-2 and Bcl-2 in the human gastric mucosa. O Jorge, FD Cuello
Carrion, A Jorge, DR Ciocca. Rev Esp Enferm Dig 2003 Feb;95(2):97-104,
89-96. 57 biopsies of patients with chronic gastritis and gastric
cancer. "PCNA [Proliferating Cell Nuclear Antigen] content of
epithelial cells was significantly higher in H. pylori infected
biopsies. Treatment aimed to eradicate H. pylori decreased the level of
PCNA-positive cells in the group of patients that became H.
pylori-negative as well as in H. pylori-positive patients. Nuclear p53
expression (used here as a surrogate marker for p53
mutation/inactivation) and c-erbB-2 expression were observed only in
the group of patients that remained with the bacteria after treatment.
A higher bcl-2 expression in lymphoid cells was observed in H.
pylori-positive biopsies, and treatment did not change the expression
of this protein. No significant expression of p21 H-ras was observed in
the studied biopsies."
New tumor necrosis factor-alpha-inducing protein released from
Helicobacter pylori for gastric cancer progression. M Suganuma, M
Kurusu, K Suzuki, A Nishizono, K Murakami, T Fujioka, H Fujiki. J
Cancer Res Clin Oncol 2005 May;131(5):305-313. "rTipalpha significantly
induced TNF-alpha gene expression and NF-kappaB activation in both Bhas
42 cells and MGT-40, and induced in vitro transformation of Bhas 42
cells. However, rdel-Tipalpha did not."
CDH1 gene promoter hypermethylation in gastric cancer: relationship to Goseki grading, microsatellite instability status, and EBV invasion. M Zazula, AM Ferreira, JP Czopek, P Kolodziejczyk, A Sinczak-Kuta, A Klimkowska, P Wojcik, K Okon, M Bialas, J Kulig, J Stachura. Diagn Mol Pathol 2006 Mar;15(1):24-29. "All cases with the MSI-high phenotype revealed CDH1 promoter hypermethylation. In MSI-low and MSS gastric cancers, this percentage was lower, reaching 71% and 41%, respectively. Moreover, the methylation status was correlated with the LOH phenotype. We detected CDH1 promoter hypermethylation in all EBV-positive gastric cancers (5/5), whereas methylation in the EBV-negative group occurred in 58% of cases."Zazula - Diagn Mol Pathol 2006 abstract / PubMed
Risk prediction of gastric cancer by analysis of aberrant DNA
methylation in non-neoplastic gastric epithelium. T Tahara, T Arisawa,
T Shibata, FY Wang, M Nakamura, M Sakata, M Nagasaka, T Takagi, Y
Kamiya, H Fujita, M Nakamura, S Hasegawa, M Iwata, K Takahama, M
Watanabe, I Hirata, H Nakano. Digestion 2007;75(1):54-61. 43 cases with
gastric cancer, versus 46 without (11 peptic ulcer, 35 gastritis). "In
all 89 subjects, CpG island methylation was found in 25.8% for p14,
52.8% for p16, 1.1% for p21. Among non-cancer patients, the methylation
frequency of the p14 gene was significantly higher in H.
pylori-positive than in H. pylori-negative patients (38.5 vs. 10.0%, p
= 0.03). The mean (+/- SD) methylation levels of the p16 gene in
non-neoplastic gastric epithelium was significantly higher in gastric
cancer cases both in all patients and in H. pylori-positive patients
(0.45 +/- 0.31 vs. 0.20 +/- 0.17; p = 0.019, 0.45 +/- 0.31 vs. 0.20 +/-
0.17; p = 0.016, respectively). The methylation level of the p16 gene
was also associated with the presence of intestinal-type gastric cancer
(p = 0.017). The methylation level of the p16 gene was significantly
higher in patients with intestinal metaplasia (IM) than those without
(p = 0.04). Furthermore, the methylation level of the p16 gene was
correlated with lower PG l/ll ratio (p = 0.04). The methylation of the
p21gene was found in only 1 patient with gastric cancer."
Chromosomal instability in gastric mucosa-associated lymphoid tissue
lymphomas: a fluorescent in situ hybridization study using a tissue
microarray approach. B Bernasconi, E Karamitopoulou-Diamantis, L
Tornillo, A Lugli, D Di Vizio, S Dirnhofer, S Wengmann, K
Glatz-Krieger, F Fend, C Capella, L Insabato, LM Terracciano. Hum
Pathol 2008 Apr;39(4):536-542. 115 cases of MALT lymphomas, 88 cases of
diffuse large B-cell lymphomas (DLBCLs, 75 with an associated MALT
lymphoma, so-called ex-MALT DLBCL, and 13 de novo), and 54 controls
cases of Helicobacter pylori-associated chronic gastritis. "Trisomies
1, 3, 12, and 18 were detected in 3.3%, 44.4%, 12.3%, and 19.2% of MALT
lymphomas and in 11.1%, 42.2%, 26.5%, and 22.0% of ex-MALT DLBCLs,
respectively. In addition, we found gains of the X chromosome in 36.4%
of MALT lymphomas, in 34.5% of ex-MALT DLBCLs, and in 36.4% of de novo
DLBCLs. Structural and/or numeric abnormalities of the MALT1 gene were
observed in 37.0% of MALT lymphomas and in 22.2% of ex-MALT DLBCLs. In
de novo DLBCL, trisomies for chromosomes 3, 12, 18, and X were found in
42.9%, 10.0%, 11.1%, and 36.4%, respectively, whereas alterations of
MALT1 (namely, translocations) were found in 20.0% of the cases. An
unexpected high and previously unreported gain of chromosome X in
gastric MALT lymphomas was found."
Accumulation of aberrant CpG hypermethylation by Helicobacter pylori
infection promotes development and progression of gastric MALT
lymphoma. T Kondo, T Oka, H Sato, Y Shinnou, K Washio, M Takano, T
Morito, K Takata, N Ohara, M Ouchida, K Shimizu, T Yoshino. Int J Oncol
2009 Sep;35(3):547-557. 21 specimens of MALT lymphoma, 5 specimens of
MALT lymphoma with large cell component (high-grade MALT lymphoma), 15
specimens of diffuse large B-cell lymphoma (DLBCL), 8 specimens of
complete remission of MALT lymphoma after eradication therapy, 5
specimens with no evidence of malignancy and PBMCs from 10 healthy
donors. "The average number of methylated genes was significantly
greater in gastric lymphomas as compared to normal controls
(P<0.001). The CpG island methylator phenotype (CIMP) was observed
in 93.3% (14/15) of DLBCLs, 100% (5/5) of high-grade MALT lymphomas and
61.9% (13/21) of MALT lymphomas; in contrast, CIMP was not found in the
control group (0%). The average number of methylated genes and the CIMP
incidence significantly increased with H. pylori infection.
Furthermore, aberrant CpG methylation of specific genes, such as p16,
MGMT and MINT31, was consistently associated with H. pylori infection."
Helicobacter pylori and EBV in gastric carcinomas: methylation status and microsatellite instability. AC Ferrasi, NA Pinheiro, SH Rabenhorst, OL Caballero, MA Rodrigues, F de Carvalho, CV Leite, MV Ferreira, MA Barros, MI Pardini. World J Gastroenterol 2010 Jan 21;16(3):312-319. "The most frequent hypermethylated gene was COX-2 (63.5%) followed by DAPK (55.7%), CDH1 (51%), CDKN2A (36%) and hMLH1 (30.3%). Intestinal and diffuse adenocarcinomas showed different methylation profiles and there was an association between methylation of E-CDH1 and H. pylori-cagA(+) in the intestinal adenocarcinoma type. MSI was correlated with hMLH1 methylation. There was an inverse correlation between DAPK hypermethylation and MSI." 5 (9.3%) of specimens were EBV-positive. "The EBV+ cases were found to be associated with H. pylori, but only one was H. pylori-cagA+. Although the number of EBV+ cases was small, most of them displayed DAPK, COX2 and CDKN2A methylation."Ferrasi - World J Gastroenterol 2010 full article / PubMed Central
Translocation of Helicobacter pylori CagA into Human B lymphocytes,
the origin of mucosa-associated lymphoid tissue lymphoma. WC Lin, HF
Tsai, SH Kuo, MS Wu, CW Lin, PI Hsu, AL Cheng, PN Hsu. Cancer Res 2010
Jul 15;70(14):5740-5748. "In this work, we showed that CagA can be
directly translocated into human B lymphoid cells by H. pylori, and the
translocated CagA undergoes tyrosine phosphorylation and binds to
intracellular SH-2. Meanwhile, the translocated CagA induces activation
of extracellular signal-regulated kinase and p38 mitogen-activated
protein kinase in human B lymphoid cells, and upregulates the
expressions of Bcl-2 and Bcl-X(L), which prevents apoptosis. These
results provide the first direct evidence for the role of CagA as a
bacterium-derived oncoprotein that acts in human B cells, and further
implies that CagA is directly delivered into B cells by H. pylori and
is associated with the development of MALT lymphomas."
MGMT and MLH1 methylation in Helicobacter pylori-infected children and adults. MC Alvarez, JC Santos, N Maniezzo, MS Ladeira, AL da Silva, IC Scaletsky, J Pedrazzoli Jr, ML Ribeiro. World J Gastroenterol 2013 May 28;19(20):3043-3051. 50 H. pylori-infected children, 97 adults with chronic gastritis, and 92 adults with gastric cancer. "Methylation was not detected in the promoter regions of MLH1 and MGMT in gastric biopsy samples from children, regardless of H. pylori infection status. The MGMT promoter was methylated in 51% of chronic gastritis adult patients and was associated with H. pylori infection (P < 0.05); this region was methylated in 66% of gastric cancer patients, and the difference in the percentage of methylated samples between these patients and those from H. pylori-infected chronic gastritis patients was statistically significant (P < 0.05). MLH1 methylation frequencies among H. pylori-infected and non-infected chronic gastritis adult patients were 13% and 7%, respectively. We observed methylation of the MLH1 promoter (39%) and increased MSI levels (68%) in samples from gastric cancer patients in comparison to samples from H. pylori-infected adult chronic gastritis patients (P < 0.001 and P < 0.01, respectively)."Alvarez - World J Gastroenterol 2013 full article / PubMed Central
Virulence of infecting Helicobacter pylori strains and intensity of mononuclear cell infiltration are associated with levels of DNA hypermethylation in gastric mucosae. BG Schneider, MB Piazuelo, LA Sicinschi, R Mera, DF Peng, JC Roa, J Romero-Gallo, AG Delgado, T de Sablet, LE Bravo, KT Wilson, W El-Rifai, RM Peek Jr, P Correa. Epigenetics 2013 Nov;8(11):1153-1161. "Among Colombian subjects at high and low risk for gastric cancer, biopsies from subjects from the high-risk region had significantly higher levels of methylation at these 5 genes than samples from subjects in the low risk region (p ≤ 0.003). When results were stratified by Helicobacter pylori infection status, infection with a cagA positive, vacA s1m1 strain was significantly associated with highest methylation levels, compared with other strains (p = 0.024 to 0.001). More severe gastric inflammation and more advanced precancerous lesions were also associated with higher levels of DNA methylation (p ≤ 0.001)... High levels of mononuclear cell infiltration were significantly related to methylation in PCDH10, RSPO2, and ZIC1 genes."Schneider - Epigenetics 2013 abstract / PubMed
DNA methylation in gastric cancer, related to Helicobacter pylori and Epstein-Barr virus. K Matsusaka, S Funata, M Fukayama, A Kaneda. World J Gastroenterol 2014 Apr 14;20(14):3916-3926. Review.Matsusaka - World J Gastroenterol 2014 full article / PubMed Central
Helicobacter pylori-infection introduces DNA double-strand breaks in host cells. K Hanada, T Uchida, Y Tsukamoto, M Watada, N Yamaguchi, K Yamamoto, S Shiota, M Moriyama, DY Graham, Y Yamaoka. Infect Immun 2014 Oct;82(10):4182-4189. "We found upregulation of ATM expression in vivo in gastric mucosal cells infected with H. pylori. Using gastric cancer cell lines, we confirmed that the H. pylori-related ATM activation was due to the accumulation of DNA double-stranded breaks (DSBs). DSBs were observed following infection with both cag pathogenicity island (PAI)-positive and -negative strains, but the effect was more robust with cag PAI-positive strains. These results are consistent with the fact that both cag PAI-positive and -negative infections are associated with gastric carcinogenesis but the risk is higher in individuals infected with cag PAI-positive strains."Hanada - Infect Immun 2014 abstract / PubMed
Helicobacter pylori Infection Causes Characteristic DNA Damage Patterns in Human Cells. M Koeppel, F Garcia-Alcalde, F Glowinski, P Schlaermann, TF Meyer. Cell Rep 2015 Jun 10 [Epub ahead of print]. "Infection impaired several DNA repair factors, the extent of which depends on a functional cagPAI. This leads to accumulation of a unique DNA damage pattern, preferentially in transcribed regions and proximal to telomeres, in both gastric cell lines and primary gastric epithelial cells. The observed pattern correlates with focal amplifications in adenocarcinomas of the stomach and partly overlaps with known cancer genes."Koeppel / Cell Rep 2015 full article
Mechanism of action of low recurrence of gastritis caused by
Helicobacter pylori with the type II urease B gene. M Badruzzaman, H
Matsui, SM Fazle Akbar, B Matsuura, M Onji. Helicobacter 2004
Apr;9(2):173-180. 45 patients with H. pylori. "The capacity of
different strains of H. pylori to induce IL-8 mRNA and IL-8 from a
human gastric cancer cell line and human peripheral blood mononuclear
cells was evaluated... These results indicate that both the lower level
of urease activity and the low IL-8-inducing capacity of type II H.
pylori might underlie the lower recurrence rate of gastritis caused by
type II H. pylori."
Comparative genomics of Helicobacter pylori isolates recovered from
ulcer disease patients in England. F Kauser, MA Hussain, I Ahmed, S
Srinivas, SM Devi, AA Majeed, KR Rao, AA Khan, LA Sechi, N Ahmed. BMC
Microbiology 2005 May 25;5(1):32. "The cag PAI is a major virulence
determinant in H. pylori and strains lacking this island are akin to
commensals rather than pathogens. Reports suggest that the presence of
a complete set of genes within the cag PAI ensures a 5-fold increased
severity of disease outcome than the intermediate PAI. We have earlier
showed that a higher number of strains from Japan had an intact cag
PAI, hence it may be thought as an important factor influencing the
outcome of the infection as a higher rate of gastric cancers was
observed in the Japanese patients... English strains mainly showed a
higher number of the toxigenic s1 type of vacA allele... Although no
association between iceA subtypes and clinical outcome has been
reported, strains carrying iceA1 produce higher levels of IL-8 in the
gastric mucosa and are more often associated with DU in the North
America and Dutch people than strains carrying iceA2."
Distinct diversity of vacA, cagA, and cagE genes of Helicobacter pylori associated with peptic ulcer in Japan. S Yamazaki, A Yamakawa, T Okuda, M Ohtani, H Suto, Y Ito, Y Yamazaki, Y Keida, H Higashi, M Hatakeyama, T Azuma. J Clin Microbiol 2005 Aug;43(8):3906-3916. "[T]he prevalence of infection with the Western group strain was significantly higher in patients with peptic ulcer (90.0%, 9/10) than in patients with chronic gastritis (22.7%, 5/22) (x2 = 12.64, P = 0.00057)."Yamazaki / J Clin Microbiol 2005 abstract
Polymorphism in the CagA EPIYA Motif Impacts Development of Gastric
Cancer. KR Jones, YM Joo, S Jang, YJ Yoo, HS Lee, IS Chung, CH Olsen,
JM Whitmire, DS Merrell, JH Cha. J Clin Microbiol 2009
Apr;47(4):959-968. "We conducted a large-scale molecular epidemiologic
analysis of South Korean strains, and herein report a statistical link
between the East Asian CagA, EPIYA-ABD genotype and development of
gastric cancer. Characterization of a subset of the Korean isolates
showed that all strains from cancer patients expressed and delivered
phosphorylateable CagA to host cells, whereas the presence of the cagA
gene did not strictly correlate to expression and delivery of CagA in
all non-cancer strains."
Gastric helicobacters in domestic animals and nonhuman primates and
their significance for human health. F Haesebrouck, F Pasmans, B
Flahou, K Chiers, M Baele, T Meyns, A Decostere, R Ducatelle. Clin
Microbiol Rev 2009 Apr;22(2):202-223. "H. suis, which has been isolated
from the stomachs of pigs, is the most prevalent gastric non-H. pylori
Helicobacter species in humans. Other gastric non-H. pylori
helicobacters colonizing the human stomach are H. felis, H. salomonis,
H. bizzozeronii, and the still-uncultivable "Candidatus Helicobacter
heilmannii." These microorganisms are often detected in the stomachs of
dogs and cats."
Differences in the genome content between H. pylori isolates from
gastritis, duodenal ulcer or gastric cancer reveal novel disease
associated genes. C Romo-González, NR Salama, J
Burgeño-Ferreira, V Ponce-Castañeda, E Lazcano-Ponce, M
Camorlinga-Ponce, J Torres. Infect Immun 2009 May;77(5):2201-2211. "The
overall number of variable genes present in a given isolate was
significantly lower for gastric cancer isolates. Thirty genes were
significantly associated with nonatrophic gastritis, duodenal ulcer, or
gastric cancer, 14 (46.6%) of which were within PZs [plasticity zones]
and the cag PAI. Two genes (HP0674 and JHP0940) were absent in all
gastric cancer isolates. Many of the disease-associated genes outside
the PZs formed clusters, and some of these genes are regulated in
response to acid or other environmental conditions."
Diversity of VacA intermediate region among Helicobacter pylori
strains from several regions of the world. C Chung, A Olivares, E
Torres, O Yilmaz, H Cohen, G Perez-Perez. J Clin Microbiol 2010
Mar;48(3):690-696. "120 strains were analyzed: 30 Chinese isolates, 35
Turkish isolates, 30 Uruguayan isolates, and 25 African-American
isolates... There was a strong correlation among CagA+, s1, and i1 in
Chinese, African-American, and Uruguayan isolates, but less correlation
among these markers in Turkish isolates. A new intermediate variant
(i3) was identified in 25.7% of Turkish strains and 3.3% of the Chinese
strains. In summary, the distribution of CagA+ and s1 correlated with
the i1 in the three populations, except in the Turkish population,
which showed a disproportionate representation of the i3 allele."
From array-based hybridization of Helicobacter pylori isolates to
the complete genome sequence of an isolate associated with MALT
lymphoma. JM Thiberge, C Boursaux-Eude, P Lehours, MA Dillies, S Creno,
JY Coppée, Z Rouy, A Lajus, L Ma, C Burucoa, A
Courillon-Mallet, H De Reuse, IG Boneca, D Lamarque, F Mégraud,
Delchier, C Médigue, C Bouchier, A Labigne, J Raymond. BMC
2010 Jun 10;11:368. "B38 has the smallest H. pylori genome described
thus far (1,576,758 base pairs containing 1,528 CDSs); it contains the
vacAs2m2 allele and lacks the genes encoding the major virulence
factors (absence of cagPAI, babB, babC, sabB, and homB)."
CagA and VacA polymorphisms are associated with distinct
pathological features in H. pylori-infected adults with peptic and
non-peptic ulcer disease. EG Panayotopoulou, DN Sgouras, KS Papadakos,
K Petraki, S Breurec, S Michopoulos, G Mantzaris, G Papatheodoridis, A
Mentis, A Archimandritis. J Clin Microbiol 2010 Jun;48(6):2237-2239.
"Polymorphic variability in H. pylori factors CagA and VacA
contributes to bacterial virulence. Presence of one CagA-EPIYA-C site
is an independent risk factor for gastroduodenal ulceration (OR: 4.647,
95% CI: 2.037-10.602), while VacAi1 allele for increased activity (OR:
5.310, 95% CI: 2.295-12.287) and severity of gastritis (OR: 3.862,
95% CI: 1.728-8.632)."
Attenuated CagA oncoprotein in Helicobacter pylori from Amerindians
in Peruvian Amazon. M Suzuki, K Kiga, D Kersulyte, J Cok, CC Hooper, H
Mimuro, T Sanada, S Suzuki, M Oyama, H Kozuka-Hata, S Kamiya, QM Zou,
RH Gilman, DE Berg, C Sasakawa. J Biol Chem 2011 Aug
26;286(34):29964-29972. "Amerindian CagA proteins induced less
production of IL-8 and
cancer-associated Mucin 2 than did those of prototype Western or East
Asian strains, and behaved as dominant negative inhibitors of action of
prototype CagA during mixed infection of Mongolian gerbils."
Characterization of Helicobacter pylori cagA and vacA genotypes
among Alaskans and their correlation with clinical disease. K Miernyk,
J Morris, D Bruden, B McMahon, D Hurlburt, F Sacco, A
Parkinson, T Hennessy, M Bruce. J Clin Microbiol 2011
Sep;49(9):3114-3121. 515 H. pylori samples from 220 Native and 66
non-Native Alaskans. "After removing mixed infections (n=17), 83% of H.
pylori had either the vacA s1m1 (120/269) or s2m2 (103/269) genotypes.
66% (68/103) of H. pylori with the vacA s2m2 genotype also contained
the cagA gene. Infection with H. pylori having the cagA gene or vacA
s1m1 genotype (compared with s1m2 and s2m2) was associated with a
decreased risk of esophagitis (p=0.003 and 0.0003, respectively).
Infection with H. pylori having vacA s1m1 genotype (compared with s1m2
and s2m2) was associated with an increased risk of PUD (p=0.003)."
Helicobacter pylori homB, but not cagA, is Associated with Gastric
Cancer in Iran. A Talebi Bezmin Abadi, A Rafiei, A Ajami, V Hosseini, T
Taghvai, KR Jones, DS Merrell. J Clin Microbiol 2011
Sep;49(9):3191-3197. 35 gastritis patients, 62 peptic ulcer patients,
gastric cancer patients. "The frequency of homB was statistically
higher in gastric cancer patients (78%) than in patients suffering from
peptic ulcers (20%) or gastritis (43%, P<0.0001). The presence of
homB was also associated with the presence of cagA (r=0.243)."
Association between Helicobacter pylori virulence factors and
gastroduodenal diseases in Okinawa, southwestern island of Japan. O
Matsunari, S Shiota, R Suzuki, M Watada, N Kinjo, K Murakami, T
Fujioka, F Kinjo, Y Yamaoka. J Clin Microbiol 2012 Mar;50(3):876-883. "Overall, 86.4% of strains possessed cagA: 70.3 % were
East-Asian-type and 16.0 % were Western-type. After adjustment by age
and sex, the presence of East-Asian-type cagA/vacA s1m1 genotypes was
significantly associated with gastric cancer compared with gastritis
(Odds Ratio = 6.68, 95 % Confidence Interval = 1.73-25.8). The
structure of Western-type CagA in Okinawa was different from that of
typical Western-type CagA found in Western countries. Intriguingly,
MLST analysis revealed that the majority of Western-type cagA strains
formed individual clusters but not hpEurope. Overall, low prevalence of
gastric cancer in Okinawa may result from the high prevalence of non
East-Asian-type cagA strains. The origin of Western-type cagA strains
in Okinawa can be different from those of Western countries."
Age of the Association between Helicobacter pylori
and Man. Y Moodley, B Linz, RP Bond, M Nieuwoudt, H Soodyall, CM
Schlebusch, S Bernhöft, J Hale, S Suerbaum, L Mugisha, SW van der
Merwe, M Achtman. PLoS Pathogens 2012;8(5): e1002693. "Three distinct
H. pylori populations are native to Africa: hpNEAfrica in Afro-Asiatic
and Nilo-Saharan speakers, hpAfrica1 in Niger-Congo speakers and
hpAfrica2 in South Africa. Rather than representing a sustained
co-evolution over millions of years, we find that the coalescent for
all H. pylori plus its closest relative H. acinonychis dates to 88–116
kya... We also find evidence for a second Out of Africa migration in
the last 52,000 years, because hpEurope is a hybrid population between
hpAsia2 and hpNEAfrica, the latter of which arose in northeast Africa
36–52 kya, after the Out of Africa migrations around 60 kya."
Phylogeographic Origin of Helicobacter pylori Determines Host-Adaptive Responses upon Coculture with Gastric Epithelial Cells. A Sheh, R Chaturvedi, DS Merrell, P Correa, KT Wilson, JG Fox. Infect Immun 2013 Jul;81(7):2468-2477. "To investigate the role of bacterial factors in H. pylori pathogenesis, global gene expression of six H. pylori isolates was analyzed during coculture with gastric epithelial cells. Clustering analysis of six Colombian clinical isolates from a region with low gastric cancer risk and a region with high gastric cancer risk segregated strains based on their phylogeographic origin. One hundred forty-six genes had increased expression in European strains, while 350 genes had increased expression in African strains. Differential expression was observed in genes associated with motility, pathogenicity, and other adaptations to the host environment. European strains had greater expression of the virulence factors cagA, vacA, and babB and were associated with increased gastric histologic lesions in patients. In AGS cells, European strains promoted significantly higher interleukin-8 (IL-8) expression than did African strains. African strains significantly induced apoptosis, whereas only one European strain significantly induced apoptosis."Sheh - Infect Immun 2013 abstract / PubMed
Reduced genome size of Helicobacter pylori originating from East Asia. QJ Dong, LL Wang, ZB Tian, XJ Yu, SJ Jia, SY Xuan. World J Gastroenterol 2014 May 21;20(19):5666-5671. "Comparative analysis of strains from different H. pylori populations revealed that the genome size of strains from East Asia decreased to 1.60 Mbp, which is significantly smaller than that from Europe or Africa. In parallel with the genome reduction, the number of protein coding genes was decreased, and the guanine-cytosine content was lowered to 38.9%."Dong - World J Gastroenterol 2014 full article / PubMed Central
Epidemiology of, and risk factors for, Helicobacter pylori infection
among 3194 asymptomatic subjects in 17 populations. The EUROGAST Study
Group. D Forman for the EUROGAST Study Group. Gut 1993
Dec;34(12):1672-1676. "The cross sectional study describes the
prevalence of infection with Helicobacter pylori as determined by a
serodiagnostic assay in over 3000 asymptomatic subjects, in two age
groups 25-34 years and 55-64 years, from 17 geographically defined
populations in Europe, North Africa, North America, and Japan, using a
common protocol for blood collection and serological testing. In all
populations combined, the prevalence of infection was higher in the
older age group (62.4%) than in the younger age group (34.9%). There
was no difference in prevalence of infection between men and women.
Subjects with higher education had considerably lower levels of
infection (34.1%) compared with subjects with education up to secondary
level (46.9%) or those with primary education only (61.6%). This trend
was confined to the older of the two age groups. In contrast a trend of
increasing prevalence of infection with increasing body mass index was
confined to the younger of the two age groups. There was no effect of
smoking or alcohol consumption on the prevalence of infection after
adjusting for the other risk factors. There was considerable variation
in the prevalence of infection between the 17 populations but, within
populations, low education standard was consistently and positively
associated with the prevalence of infection."
Importance of childhood socioeconomic status on the current
prevalence of Helicobacter pylori infection. HM Malaty, DY Graham. Gut
1994 Jun;35(6):742-745. Anti-H pylori IgG in 150 healthy black and
Hispanic people aged between 19 and 49 years. "The H pylori prevalence
was inversely related to the social class during childhood. It was 85%
for class I, 52% for combined classes II and III, and 11% for classes
IV and V combined. The inverse correlation remained after adjustments
were made for the present social class and age. H pylori infection was
also related to crowded living conditions (odds ratio 4.5: 95%
confidence interval 3.3, 5.7) for those who had had the most crowded
living conditions during childhood)."
Relation of adult lifestyle and socioeconomic factors to the prevalence of Helicobacter pylori infection. P Moayyedi, ATR Axon, R Feltbower, S Duffett, W Crocombe, D Braunholtz, IDG Richards, AC Dowell, D Forman, for the Leeds HELP Study Group. International Journal of Epidemiology 2002;31(3):624-631. "The prevalence of H. pylori infection had a statistically significant association with present social class in an unadjusted analysis. Present social class is correlated with childhood social class (Pearson's correlation coefficient = 0.22, P < 0.0001) and the unadjusted results of present social class could be confounded by childhood socioeconomic conditions. However, the prevalence of H. pylori infection increased with decreasing social class even within levels of childhood social class." "The proportion of subjects infected increased with increasing numbers of cigarettes smoked (Table 4) but when adjusted for childhood and adult socioeconomic status the 95% CI for the OR did not include unity only in those that smoked >35 cigarettes/day."Moayyedi / Int J Epidemiol 2002 full article
The Prevalence of Helicobacter pylori Remains High in African American and Hispanic Veterans. T Nguyen, D Ramsey, D Graham, Y Shaib, S Shiota, M Velez, R Cole, B Anand, M Vela, HB El-Serag. Helicobacter 2015 Feb 17 [Epub ahead of print]. 1200 veterans age 40-80. "H. pylori was positive in 347 (28.9%) and was highest among black males aged 50-59 (53.3%; 44.0-62.4%), followed by Hispanic males aged 60-69 (48.1%; 34.2-62.2%), and lowest in non-Hispanic white males aged 40-49 (8.2%; 2.7-20.5%)... Irrespective of age group, patients born during 1960-1969 had a lower risk of H. pylori (adjusted OR, 0.45; 95% CI, 0.22-0.96) compared to those born in 1930-1939. Those with some college education were less likely to have H. pylori compared to those with no college education (adjusted OR 0.51; 95% CI, 0.37-0.69)."Nguyen - Helicobacter 2015 abstract / PubMed
"A study of 90 pregnant women in Puerto Rico found that those who experienced severe nausea and vomiting were 10 times more likely to have the Helicobacter pylori bacterium in their stomachs than women who did not feel sick... 'We found H pylori in 83% of the women with morning sickness, but only 7% of the controls were positive," said Dr Nilda Santiago, who conducted the study with colleagues at the Ponce School of Medicine in Puerto Rico. (Morning sickness linked to ulcer bug. BBC News, Oct. 21, 2000.)Morning Sickness linked to ulcer bug, Oct. 21, 2000 / BBC News
Helicobacter pylori is not the cause of sudden infant death syndrome
(SIDS). GY Ho, HM Windsor, B Snowball, BJ Marshall. Am J Gastroenterol
2001 Dec;96(12):3288-3294. HP in 53% (9/17) SIDS samples vs. 57% (4/7)
"Since at least 1906, doctors had reported seeing curved bacteria in
the stomach of patients who died with ulcers but less often in people
without them. Still, doctors paid little attention to the observation
in the belief that bacteria could not thrive in the acid-filled
stomach. Doctors assumed that the bacteria appeared after death... Dr.
Freedberg examined pieces of stomach removed during operations for
ulcers and other ailments. Using a silver chemical stain, he identified
the bacteria in more than a third of ulcer patients, but his
colleagues’ efforts to culture them failed. In a 2005 interview with
The New York Times, Dr. Freedberg said he was “very upset” when others
did not confirm the findings he published because it implied that his
work was wrong. Even his boss, Dr. Herrman Blumgart, suggested that he
had erred and discouraged him from continuing the research. Other
doctors tried and failed to find the evidence until 1983, when two
Australians, Dr. Barry J. Marshall and Dr. J. Robin Warren, identified
the bacteria, now known as Helicobacter pylori, among ulcer patients.
In 2005, the two Australians received Nobel Prizes in medicine for that
work. The two later met. In an interview in The Times in 2005, Dr.
Marshall said that if Dr. Freedberg had been able to pursue his ulcer
research, researchers would have developed treatments for ulcers
decades earlier. 'They would have won the Nobel Prize about 1951, as I
was getting born,' Dr. Marshall said." (A. Stone Freedberg, Pioneer in
Study of Ulcers, Dies at 101. By Lawrence K. Altman. New York Times,
Aug. 23, 2009.)
were proposed to be an infectious disease in 1914: "Two
important announcements were made to the members of the International
Surgical Association at yesterday morning's session of the fourth
congress, which is meeting at the Hotel Astor, during a discussion of
ulcers of the stomach and duodenum. The first tended to show that these
ulcers, which are comparatively common in persons of middle age, belong
to the category of infectious diseases... Dr. Arthur D. Bevan, Professor of
Surgery at the University of Chicago, made the announcement relative to
the origin of gastric and duodenal ulcers. He said that his colleague,
Dr. Edward C. Rosenau, who occupies the Chair of Pathology at the
Chicago University and has a wide reputation as a research worker, has
demonstrated that these ulcers could be caused by the injection of
bacteria taken from other ulcers. The injections were made
intravenously, that is, directly into the blood, whereupon the disease
made its appearance at the usual sites of ulceration, both in the
stomach and intestines of animals... Dr. H. Hartmann and Dr. P.
Lecène of Paris presented a joint paper in which they asserted
that duodenal ulcer was more frequent than supposed several years ago.
In their opinion, however, its frequency has been exaggerated. They
have found one ulcer of the duodenum to eight or ten of the stomach.
They also found that about one-fifth of these cases of the
callous ulcers of the stomach degenerate into cancer." (Say Gastric
Ulcers May Be Infectious. New York Times, Apr. 15, 1914.) In 1916, Dr.
Francis Carter Wood, the president of the American
Society for the Control of Cancer and later one of the original
members of the National Advisory Cancer Council of the National Cancer
Institute, proclaimed that 'cancer was not a germ disease nor in any
way allied to germ diseases.'
See how the quacks continue to spew the discredited lie that smoking causes ulcers! "There are other causes of peptic ulcer that are unrelated to H. pylori infection, but these are less common. In particular, the chronic use of non steroidal antiinflammatory drugs (NSAIDs) and cigarette smoking can be causes of both ulcer formation and failure of treatment." (What causes ulcers. By Melissa Stoppler, Barbara K. Hecht. MedicineNet.com Feb. 10, 2005.) Oh, and by the way, in light of the billions of dollars of "damages" that US corporations have shoveled out to the health fascist parasites for their pretended crimes against public health - HOW MUCH MONEY HAVE THE HEALTH FASCIST LICE BEEN FORCED TO PAY OUT FOR THEIR DECADES-LONG SUPPRESSION OF THE TRUTH THAT HELICOBACTER PYLORI IS THE REAL CAUSE OF ULCERS? They have not paid one cent, and there's not even the rumor of a lawsuit; nor have they even been subjected to a single word of reproach from their fawning mass media toadies.What Causes Ulcers / Medicine.Net
"It is amazing that this major problem of mankind was largely defined and solved by clinical gastroenterologists essentially without support from the biomedical research establishment... It is time that our biomedical research establishment tempers its traditional focus on molecular mechanisms of disease and addresses questions that appear 'clinical' and 'should be funded by drug companies.'" And, "...many of these same skeptics helped perform the needed scientific studies (unfunded by traditional sources) to validate the fact that peptic ulcers are one manifestation of an infectious disease... We can no longer ignore the evidence that peptic ulcers are caused by H pylori and that they can be cured." Peura DA, Graham DY. Editorial. Helicobacter pylori: Consensus Reached: Peptic ulcer is on the way to becoming an historic disease. Am J Gastroenterol 1994 Aug;89(8):1137. National Institutes of Health, Helicobacter pylori Consensus Development Conference, Feb. 7-9, 1994.
Let us remember: While the clinical gastroenterologists were investigating and solving this problem, all by themselves, the health establishment was pouring money into studies on acid secretion, gastrin, catecholamines, epidermal growth factors, prostaglandins, bile acids, pepsinogen, thromboxane, gastric emptying time, and everything else they could think of, for the sole purpose of trying to find some mechanism whereby they could claim that smoking causes ulcers. (They had, of course, long before declared that smoking causes ulcers without having such a mechanism; they merely bluffed the public that they did: McCarthy DM. Editorial re Sontag: "Smoking and Ulcers -- Time to Quit." New England Journal of Medicine 1984 Sep. 13;311(11):726-727).McCarthy - NEJM 1984 / UCSF (pdf, 3 pp)
If it were up to the establishment, ulcers would still be a lifelong affliction, treated with H2 blockers and proton pump inhibitors and drivelous rhetoric about smoking, diet and stress, while they pat themselves on the back for the imagined sophistication of their intervention in the molecular bases of the disease.
"The natural history of gastric and duodenal ulcers is to recur at a rate of 50 to 90% in the year following the ulcer healing... Although all the answers are not yet in, at least a hundred clinical trials have now been completed and the results have been consistent. Cure of H. pylori infection results in virtual elimination of ulcer recurrence... Factors previously used to predict ulcer recurrence such as smoking... are no longer important. The new dictum is 'no H pylori, no ulcer.'" "The discovery that H pylori was a cause of gastritis elicited major international interest and clinical studies have been done in all parts of the world; probably the fewest number of investigations have come from the United States." Graham DY. Review. Benefits from elimination of Helicobacter pylori infection include major reduction in the incidence of peptic ulcer disease, gastric cancer, and primary gastric lymphoma. Prev Med 1994 Sep;23(5):712-716).
Helicobacter pylori also causes stomach cancer. Interestingly, Mr. Mary Lasker (Albert) died of stomach cancer in 1952. This letter which appeared in The Atlantic in response to Judith Hooper's "A New Germ Theory" suggests that perhaps his life, and certainly the lives of a multitude of others, could have been saved, if Germ Theory had prevailed over the dogma the Laskers imposed over the National Institutes of Health by means of their wealth and political connections: "In 1946 I was a first-year medical resident at the New York Hospital when the senior attending physician, Constance Guion, called to tell me that she was admitting a patient who was suffering with an acute, painful peptic stomach ulcer. Dr. Guion instructed me to start the patient on 'that new antibiotic, aureomycin,' the forerunner of the modern tetracycline family of antibiotics. 'But Dr. Guion,' I expostulated, 'I thought you said she had an ulcer. Why would you want to treat her with an antibiotic?' Dr. Guion replied, 'The latest research over at Mt. Sinai shows that 'peptic' ulcers are actually caused by germs, now do as I say and give her the aureomycin.' The patient went home three days later free of symptoms." (Paul Fremont Smith, Physician in Chief, Emeritus, New England Baptist Hospital, Boston, Massachusetts.)
Let this put to rest the faith of those naive and trusting souls who cling to the belief that, since the Laskers and their cronies themselves suffered and died from the diseases which they refused to consider might be caused by infection, they must have acted in good faith, and that their professed desires to find cures were sincere. In fact, the grip of their irrational ideology of infection-denialism is stronger than reason, or even their own instinct of self-preservation. They are the pure essence of evil, and have caused enormous harm not only to themselves but to society as well.Letters re "A New Germ Theory"
"Dr. [Harvey] Cushing
established definitely that the cause of stomach ulcers is due to
disturbances in that portion of the brain which governs the automatic
processes of living. Disturbances are set up in the diencephalon, a
part of the brain which is the seat of the primitive emotions and which
controls the digestive processes. He announced this discovery at
Toronto in 1931 in a lecture at the University of Toronto. In the
course of his long surgical career at Boston, Dr. Cushing has operated
upon a number of Berkshire patients." (Special Honor for Dr. Cushing.
North Adams Transcript, May 8, 1935.)
"Many doctors continue to claim that these bacteria are irrelevant, even in duodenal and gastric ulcer, blithely ignoring the hundreds of papers (990 during 1992 alone) indicating its importance." Goodwin CS. Comment. Gastric cancer and Helicobacter pylori: the whispering killer? Lancet 1993 Aug 28;342(8870):507-508).
(Christensen AH, Gjirup T, Andersen IB, Matzen P. Opinions in Denmark on the causes of peptic ulcer disease. A survey among Danish physicians and patients. Scan J Gastroenterol 1994 Apr;29(4):305-308).
Perhaps this will help put the anti-smokers' claim that "the tobacco companies lied about the health risks of smoking" into a radically different perspective.
This is the sworn testimony of Dr. Jonathan Samet, star witness for the anti-smoking side in Minnesota's lawsuit against the tobacco industry, on February 12, 1998, concerning the supposed causal role of smoking in peptic ulcer disease, and its pretended costs to the state and to Blue Cross Blue Shield. Note that Samet is now (2012) the head of the FDA Committee on Tobacco.
BY MR. HAMLIN [attorney for the State of Minnesota and Blue Cross Blue Shield]:
Q. Doctor, I want to address now the last disease, which is peptic ulcer. What is peptic ulcer?
A. Peptic ulcer is -- refers to the erosions or ulcers that occur usually at the end of the stomach where the stomach empties out into the duodenum, and then in the first part of the duodenum, that's the very first part of the small intestine.
Q. What are the symptoms?
A. The symptoms may include pain when the stomach is empty. People may present with bleeding if the ulcer becomes deep enough and erodes into a blood vessel. There may actually be severe bleeding. People may have discomfort on -- on eating, weight loss, among other symptoms.
Q. And what treatments are used to treat peptic ulcer?
A. Typically, first the diagnosis needs to be made by usually at this point looking into the stomach with a tube very much like the bronchoscope, except for looking into the esophagus and stomach and duodenum. The basic treatment is medication, and for those individuals who have bleeding, surgery may be necessary to actually identify the bleeding point and sew it over so that the bleeding can be stopped.
Q. Based on your clinical experience, how much do these treatments cost?
A. Well it really would vary depending on need for medication alone up to emergency surgery.
Q. Now did you do an investigation of the published literature regarding smoking and peptic ulcer?
Q. You did that in connection with your investigation in this case?
Q. And did you review reports of the Surgeon General?
Q. Has the Surgeon General concluded that smoking is a cause of peptic ulcer?
Q. And were they met?
Q. And are those studies in the database that you've completed in this case?
Q. Doctor, based on your education, training, your expertise in the science of smoking and health, and your review of the literature on the science of smoking and health, do you have an opinion regarding whether smoking is a cause of peptic ulcer?
Q. What is that opinion?
A. That smoking is a cause of peptic ulcer.
In fact, Dr. Samet's obsolete notions of the diagnosis and treatment of peptic ulcer are in flagrant disregard of the directive to physicians issued several years earlier in the Consensus Statement of the National Institutes of Health. A patient under his care who suffered the dire consequences he related would be fully entitled to sue the son-of-a-bitch for malpractice, and to take his arm and his leg and every other appendage for damages. In fact, for a patient with the symptoms described, the first step would be an inexpensive blood test for Helicobacter pylori, costing about twenty five dollars, and not an endoscopy costing from several hundred to several thousand dollars, depending on how it's inflated. And if the patient is positive for Helicobacter, as nearly all are except those cases caused exclusively by the use of non-steroidal anti-inflammatory medications for other ailments such as arthritis, the treatment would entail a couple hunded bucks for two weeks of antibiotics, and not, as in Jonathan Samet's brand of (mis)treatment, hundreds of dollars a month for proton pump inhibitors for the rest of the patient's life.
Furthermore, the Surgeon General's pretense that "smoking causes ulcers" is founded on defective studies which falsely pretend that, because ulcers were found to be more common in smokers, this constitutes proof that smoking causes them. In fact, the state-of-the-art opinion is that the vast majority of infections by Helicobacter pylori occur very early in life, long before people become smokers. Therefore, smoking cannot even play the role speculated by the anti-smoking pseudo-scientists of increasing peoples' susceptibility to infection. The reason that ulcers are more common in smokers is that Helicobacter pylori infection is associated with lower socioeconomic origins, and smokers are more likely to have such origins than nonsmokers.
To further the outrage, at no time during this kangaroo trial was Samet's testimony challenged by the attorney for the tobacco industy, Mr. Garnick. Even the lowliest public defender could have done a better job than Garnick did. Nor did the tobacco lawyers ever challenge Samet's similar perjury regarding other so-called smoking-related diseases" which are actually caused by infection. Plus, the tobacco industry settled rather than let the case go to the jury, even though it was believed by many observers that the tobacco industry would win. This is sufficient proof to any intelligent person that the tobacco industry lawyers threw the fight to the anti-smokers on purpose -- at a cost of $368 billion to the smokers of America.
On the website of the Harvard School of Public Health, which purports to give legitimate medical advise about how to avoid cancer, there is no mention of Helicobacter pylori as a cause of stomach cancer (never mind Epstein-Barr virus)! As of May 18, 2002, these quacks maintain that salt, blood type, family history, and salt are significant risks for stomach cancer. (Link died http://www.yourcancerrisk.harvard.edu/hccpquiz.pl?func=show&quiz=stomach&page=risk_list.) As of May 16, 2013, they admit that H. pylori is a cause of stomach cancer, but of too low a percentage ("about half"). And they still blame smoking and ignore EBV.Fact Sheet - Stomach Cancer / Harvard School of Public Health
The Harvard School of Public Health
commits scientific fraud by using phony "smoking risks" based on
lifestyle questionnaire studies to manufacture a bogus estimate of
gastric cancer incidence. They're also guilty of ignoring the fact that
rates of gastric cancer declined while smoking increased.
Effects of Helicobacter pylori infection and smoking on gastric cancer
incidence in China: a population-level analysis of trends and
projections. JM Yeh, SJ Goldie, KM Kuntz, M Ezzati. Cancer Causes
Control 2009 Dec;20(10):2021-2029.
Prospective study on the relation of cigarette smoking with cancer
of the liver and stomach in an endemic region. T Mizoue, N Tokui, K
Nishisaka, S Nishisaka, I Ogimoto, M Ikeda, T Yoshimura. Int J
Epidemiol 2000 Apr;29(2):232-237. This study considered no biomarkers
whatsoever for either hepatitis viruses or stomach infections, and its
mere publication reflects the dishonesty of the editors of the journal,
who in 2006 include George Davey-Smith, co-author of a paper
demonstrating how confounding occurs in
exactly such circumstances.
Alton Ochsner recites the standard lies that reigned for decades, falsely blaming ulcers on "excess acid" supposedly produced by a faulty lifestyle. (Lung Cancer and Its Relationship to Smoking, by Alton Ochsner. American Temperance Society, 1951, pp. 4-6.)Ochsner, 1951 / UCSF (pdf, 16 pp)
Peter Jennings and the News. WMAL TV,
Washington DC, ABC Network.
May 1, 1967 6:30 P.M. TOBACCO INDUSTRY REJOINDER FRAN REYNOLDS
(SUBSTITUTING) "Another report today that smoking is bad for your
health. The Public Health Service has completed a new study, cigarette
smokers, according to this report, are more prone to develope chronic
illness such as heart disease, ulsers [sic] and emphysema, but the
tobacco industry has come right back with a rejoinder that there is no
proof its the smoking that actually causes the diseases."