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Gut. Sep 2001; 49(3): 347–353.
PMCID: PMC1728434

Gastric cancer and Helicobacter pylori: a combined analysis of 12 case control studies nested within prospective cohorts

Abstract

BACKGROUND—The magnitude of the association between Helicobacter pylori and incidence of gastric cancer is unclear. H pylori infection and the circulating antibody response can be lost with development of cancer; thus retrospective studies are subject to bias resulting from classification of cases as H pylori negative when they were infected in the past.
AIMS—To combine data from all case control studies nested within prospective cohorts to assess more reliably the relative risk of gastric cancer associated with H pylori infection. To investigate variation in relative risk by age, sex, cancer type and subsite, and interval between blood sampling and cancer diagnosis.
METHODS—Studies were eligible if blood samples for H pylori serology were collected before diagnosis of gastric cancer in cases. Identified published studies and two unpublished studies were included. Individual subject data were obtained for each. Matched odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated for the association between H pylori and gastric cancer.
RESULTS—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.


Keywords: gastric cancer; Helicobacter pylori; cardia cancer; pooled analysis

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Selected References

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  • Webb PM, Forman D. Helicobacter pylori as a risk factor for cancer. Baillieres Clin Gastroenterol. 1995 Sep;9(3):563–582. [PubMed]
  • Hansson LE, Engstrand L, Nyrén O, Evans DJ, Jr, Lindgren A, Bergström R, Andersson B, Athlin L, Bendtsen O, Tracz P. Helicobacter pylori infection: independent risk indicator of gastric adenocarcinoma. Gastroenterology. 1993 Oct;105(4):1098–1103. [PubMed]
  • Parsonnet J, Friedman GD, Vandersteen DP, Chang Y, Vogelman JH, Orentreich N, Sibley RK. Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med. 1991 Oct 17;325(16):1127–1131. [PubMed]
  • Nomura A, Stemmermann GN, Chyou PH, Kato I, Perez-Perez GI, Blaser MJ. Helicobacter pylori infection and gastric carcinoma among Japanese Americans in Hawaii. N Engl J Med. 1991 Oct 17;325(16):1132–1136. [PubMed]
  • Parsonnet J, Vandersteen D, Goates J, Sibley RK, Pritikin J, Chang Y. Helicobacter pylori infection in intestinal- and diffuse-type gastric adenocarcinomas. J Natl Cancer Inst. 1991 May 1;83(9):640–643. [PubMed]
  • Simán JH, Forsgren A, Berglund G, Florén CH. Association between Helicobacter pylori and gastric carcinoma in the city of Malmö, Sweden. A prospective study. Scand J Gastroenterol. 1997 Dec;32(12):1215–1221. [PubMed]
  • Talley NJ, Zinsmeister AR, Weaver A, DiMagno EP, Carpenter HA, Perez-Perez GI, Blaser MJ. Gastric adenocarcinoma and Helicobacter pylori infection. J Natl Cancer Inst. 1991 Dec 4;83(23):1734–1739. [PubMed]
  • Chow WH, Blaser MJ, Blot WJ, Gammon MD, Vaughan TL, Risch HA, Perez-Perez GI, Schoenberg JB, Stanford JL, Rotterdam H, et al. An inverse relation between cagA+ strains of Helicobacter pylori infection and risk of esophageal and gastric cardia adenocarcinoma. Cancer Res. 1998 Feb 15;58(4):588–590. [PubMed]
  • Karnes WE, Jr, Samloff IM, Siurala M, Kekki M, Sipponen P, Kim SW, Walsh JH. Positive serum antibody and negative tissue staining for Helicobacter pylori in subjects with atrophic body gastritis. Gastroenterology. 1991 Jul;101(1):167–174. [PubMed]
  • Crabtree JE, Wyatt JI, Sobala GM, Miller G, Tompkins DS, Primrose JN, Morgan AG. Systemic and mucosal humoral responses to Helicobacter pylori in gastric cancer. Gut. 1993 Oct;34(10):1339–1343. [PMC free article] [PubMed]
  • Forman D, Newell DG, Fullerton F, Yarnell JW, Stacey AR, Wald N, Sitas F. Association between infection with Helicobacter pylori and risk of gastric cancer: evidence from a prospective investigation. BMJ. 1991 Jun 1;302(6788):1302–1305. [PMC free article] [PubMed]
  • Lin JT, Wang LY, Wang JT, Wang TH, Yang CS, Chen CJ. A nested case-control study on the association between Helicobacter pylori infection and gastric cancer risk in a cohort of 9775 men in Taiwan. Anticancer Res. 1995 Mar-Apr;15(2):603–606. [PubMed]
  • Aromaa A, Kosunen TU, Knekt P, Maatela J, Teppo L, Heinonen OP, Härkönen M, Hakama MK. Circulating anti-Helicobacter pylori immunoglobulin A antibodies and low serum pepsinogen I level are associated with increased risk of gastric cancer. Am J Epidemiol. 1996 Jul 15;144(2):142–149. [PubMed]
  • Webb PM, Yu MC, Forman D, Henderson BE, Newell DG, Yuan JM, Gao YT, Ross RK. An apparent lack of association between Helicobacter pylori infection and risk of gastric cancer in China. Int J Cancer. 1996 Sep 4;67(5):603–607. [PubMed]
  • Yuan JM, Yu MC, Xu WW, Cockburn M, Gao YT, Ross RK. 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. Cancer Epidemiol Biomarkers Prev. 1999 Jul;8(7):621–624. [PubMed]
  • Watanabe Y, Kurata JH, Mizuno S, Mukai M, Inokuchi H, Miki K, Ozasa K, Kawai K. Helicobacter pylori infection and gastric cancer. A nested case-control study in a rural area of Japan. Dig Dis Sci. 1997 Jul;42(7):1383–1387. [PubMed]
  • Hansen S, Melby KK, Aase S, Jellum E, Vollset SE. Helicobacter pylori infection and risk of cardia cancer and non-cardia gastric cancer. A nested case-control study. Scand J Gastroenterol. 1999 Apr;34(4):353–360. [PubMed]
  • Forman D, Webb P, Parsonnet J. H pylori and gastric cancer. Lancet. 1994 Jan 22;343(8891):243–244. [PubMed]
  • Huang JQ, Sridhar S, Chen Y, Hunt RH. Meta-analysis of the relationship between Helicobacter pylori seropositivity and gastric cancer. Gastroenterology. 1998 Jun;114(6):1169–1179. [PubMed]
  • Eslick GD, Lim LL, Byles JE, Xia HH, Talley NJ. Association of Helicobacter pylori infection with gastric carcinoma: a meta-analysis. Am J Gastroenterol. 1999 Sep;94(9):2373–2379. [PubMed]
  • Wald NJ, Law MR, Morris JK, Bagnall AM. Helicobacter pylori infection and mortality from ischaemic heart disease: negative result from a large, prospective study. BMJ. 1997 Nov 8;315(7117):1199–1201. [PMC free article] [PubMed]
  • Limburg P, Qiao Y, Mark S, Wang G, Perez-Perez G, Blaser M, Wu Y, Zou X, Dong Z, Taylor P, et al. Helicobacter pylori seropositivity and subsite-specific gastric cancer risks in Linxian, China. J Natl Cancer Inst. 2001 Feb 7;93(3):226–233. [PubMed]
  • Yamagata H, Kiyohara Y, Aoyagi K, Kato I, Iwamoto H, Nakayama K, Shimizu H, Tanizaki Y, Arima H, Shinohara N, et al. Impact of Helicobacter pylori infection on gastric cancer incidence in a general Japanese population: the Hisayama study. Arch Intern Med. 2000 Jul 10;160(13):1962–1968. [PubMed]
  • Tersmette AC, Offerhaus GJ, Tersmette KW, Giardiello FM, Moore GW, Tytgat GN, Vandenbroucke JP. Meta-analysis of the risk of gastric stump cancer: detection of high risk patient subsets for stomach cancer after remote partial gastrectomy for benign conditions. Cancer Res. 1990 Oct 15;50(20):6486–6489. [PubMed]
  • Tersmette AC, Goodman SN, Offerhaus GJ, Tersmette KW, Giardiello FM, Vandenbroucke JP, Tytgat GN. Multivariate analysis of the risk of stomach cancer after ulcer surgery in an Amsterdam cohort of postgastrectomy patients. Am J Epidemiol. 1991 Jul 1;134(1):14–21. [PubMed]
  • Lagergren J, Bergström R, Lindgren A, Nyrén O. Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med. 1999 Mar 18;340(11):825–831. [PubMed]
  • Botterweck AA, Schouten LJ, Volovics A, Dorant E, van Den Brandt PA. Trends in incidence of adenocarcinoma of the oesophagus and gastric cardia in ten European countries. Int J Epidemiol. 2000 Aug;29(4):645–654. [PubMed]
  • Møller H. Incidence of cancer of oesophagus, cardia and stomach in Denmark. Eur J Cancer Prev. 1992 Feb;1(2):159–164. [PubMed]
  • Hansson LE, Sparén P, Nyrén O. Increasing incidence of carcinoma of the gastric cardia in Sweden from 1970 to 1985. Br J Surg. 1993 Mar;80(3):374–377. [PubMed]
  • Powell J, McConkey CC. The rising trend in oesophageal adenocarcinoma and gastric cardia. Eur J Cancer Prev. 1992 Apr;1(3):265–269. [PubMed]
  • Devesa SS, Blot WJ, Fraumeni JF., Jr Changing patterns in the incidence of esophageal and gastric carcinoma in the United States. Cancer. 1998 Nov 15;83(10):2049–2053. [PubMed]
  • Hansen S, Wiig JN, Giercksky KE, Tretli S. Esophageal and gastric carcinoma in Norway 1958-1992: incidence time trend variability according to morphological subtypes and organ subsites. Int J Cancer. 1997 May 2;71(3):340–344. [PubMed]

Figures and Tables

Figure 1
Matched odds ratios (OR) and 95% confidence intervals (CI) for the association between Helicobacter pylori infection and gastric cancer, overall and by study. The area of the square is proportional to the study size. The diamond shows the OR value for ...
Figure 2
Matched odds ratios (OR) and 95% confidence intervals (CI) for the association between Helicobacter pylori infection and non-cardia gastric cancer, overall and by study. The area of the square is proportional to the study size. The diamond shows the ...
Figure 3
Matched odds ratios (OR) and 95% confidence intervals (CI) for the association between Helicobacter pylori infection and cardia cancer, overall and by study. The area of the square is proportional to the study size. The diamond shows the OR value for ...

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