During Feb. 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.)

Subsequently, a 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 countries."

"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 pylori.

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.

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 current smoking."

Pathogenesis of Helicobacter pylori infection. JG Kusters, AHM van Vliet, EJ Kuipers. Clin Microbiol Rev 2006 July 1;19(3):449-490. Review.

Helicobacter pylori and gastric cancer

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."

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)."

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 tumors."

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 with malignancy."

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, 1.51–9.30)."

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. pylori."

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."

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, 2.2-7.7)."

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 Helicobacter pylori seropositivity in gastric cancer patients" [emphasis added].

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 addressed this 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 CagA-negative)."

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 added].

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."

[Note: None of the studies to date have mentioned the involvement of Epstein-Barr virus in gastric carcinoma.]

Helicobacter pylori and lymphomas

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 studies."

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).

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%)."

Antibiotic treatment of gastric lymphomas

[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 had disappeared."

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 monoclonality relapsed."

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."

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.

Helicobacter pylori and ulcers

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 ulcers)."

Possible mechanisms

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.

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.

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. Tipalpha activates NF-kappa B.

HP strains have differing pathogenic effects

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.

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)."

Helicobacter pylori and social class

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."

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."

The Helicobacter Pylori Foundation

"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.)

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) non-SIDS samples.

Heliquotes

Ulcers were first 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.

"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).

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.

"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).

• 97% of doctors versus 41% of patients believed "side effects of medicine" cause ulcers
• 95% of doctors versus 44% of patients believed smoking causes ulcers.
• 82% of doctors versus 75% of patients believed "psychologic factors" cause ulcers.
• 39% of doctors verus 3% of patients believed infections cause ulcers.
• 3% of doctors versus 8% of patients believed "supernatural factors" cause ulcers.

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.

Jonathan Samet committed perjury at the Minnesota tobacco trial!

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.

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?

A. Yes.

Q. You did that in connection with your investigation in this case?

A. Yes.

Q. And did you review reports of the Surgeon General?

A. Yes.

Q. Has the Surgeon General concluded that smoking is a cause of peptic ulcer?

A. Yes.

Q. And were they met?

A. Yes.

Q. And are those studies in the database that you've completed in this case?

A. Yes.

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?

A. Yes.

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.

Shame on the Harvard School of Public Health!

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. Their alliance with the Lasker Syndicate has made them fat cats of NIH funding, for their Nurses Health Study of diet and cancer risk.

Shame on the International Journal of Epidemiology

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

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.)

ABC News, 1967

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."

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cast 08-10-07