BACKGROUND. Infection with Helicobacter pylori has been linked with chronic atrophic gastritis, an inflammatory precursor of gastric adenocarcinoma. In a nested case-control study, we explored whether H. pylori infection increases the risk of gastric carcinoma. METHODS. From a cohort of 128,992 persons followed since the mid-1960s at a health maintenance organization, 186 patients with gastric carcinoma were selected as case patients and were matched according to age, sex, and race with 186 control subjects without gastric carcinoma. Stored serum samples collected during the 1960s were tested for IgG antibodies to H. pylori by enzyme-linked immunosorbent assay. Data on cigarette use, blood group, ulcer disease, and gastric surgery were obtained from questionnaires administered at enrollment. Tissue sections and pathology reports were reviewed to confirm the histologic results. RESULTS. The mean time between serum collection and the diagnosis of gastric carcinoma was 14.2 years. Of the 109 patients with confirmed gastric adenocarcinoma (excluding tumors of the gastroesophageal junction), 84 percent had been infected previously with H. pylori, as compared with 61 percent of the matched control subjects (odds ratio, 3.6; 95 percent confidence interval, 1.8 to 7.3). Tumors of the gastroesophageal junction were not linked to H. pylori infection, nor were tumors in the gastric cardia. H. pylori was a particularly strong risk factor for stomach cancer in women (odds ratio, 18) and blacks (odds ratio, 9). A history of gastric surgery was independently associated with the development of cancer (odds ratio, 17; P = 0.03), but a history of peptic ulcer disease was negatively associated with subsequent gastric carcinoma (odds ratio, 0.2; P = 0.02). Neither blood group nor smoking history affected risk. CONCLUSIONS. Infection with H. pylori is associated with an increased risk of gastric adenocarcinoma and may be a cofactor in the pathogenesis of this malignant condition.
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Department of Medicine, Stanford University School of Medicine, Calif. 94305-5425.
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(2005). Impact of Clarithromycin Resistance on Eradication of Helicobacter pylori in Infected Adults. Antimicrob. Agents Chemother.
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(2005). Orchestration of Aberrant Epithelial Signaling by Helicobacter pylori CagA. Sci Signal
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Lin, S.-N., Ayada, K., Zhao, Y., Yokota, K., Takenaka, R., Okada, H., Kan, R., Hayashi, S., Mizuno, M., Hirai, Y., Fujinami, Y., Oguma, K.
(2005). Helicobacter pylori heat-shock protein 60 induces production of the pro-inflammatory cytokine IL8 in monocytic cells. J Med Microbiol
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Preciado, D., Caicedo, E., Jhanjee, R., Silver, R., Harris, G., Juhn, S. K., Choo, D. I., Ondrey, F.
(2005). Pseudomonas aeruginosa Lipopolysaccharide Induction of Keratinocyte Proliferation, NF-{kappa}B, and Cyclin D1 Is Inhibited by Indomethacin. J. Immunol.
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Nakagawa, S., Osaki, T., Fujioka, Y., Yamaguchi, H., Kamiya, S.
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Terio, K. A., Munson, L., Marker, L., Aldridge, B. M., Solnick, J. V.
(2005). Comparison of Helicobacter spp. in Cheetahs (Acinonyx jubatus) with and without Gastritis. J. Clin. Microbiol.
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Aoki, M, Yamamoto, K, Noshiro, H, Sakai, K, Yokota, J, Kohno, T, Tokino, T, Ishida, S, Ohyama, S, Ninomiya, I, Uesaka, K, Kitajima, M, Shimada, S, Matsuno, S, Yano, M, Hiratsuka, M, Sugimura, H, Itoh, F, Minamoto, T, Maehara, Y, Takenoshita, S, Aikou, T, Katai, H, Yoshimura, K, Takahashi, T, Akagi, K, Sairenji, M, Yamamura, Y, Sasazuki, T
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Kalach, N., Mention, K., Guimber, D., Michaud, L., Spyckerelle, C., Gottrand, F.
(2005). Helicobacter pylori Infection Is Not Associated With Specific Symptoms in Nonulcer-Dyspeptic Children. Pediatrics
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Kobayashi, M., Mitoma, J., Nakamura, N., Katsuyama, T., Nakayama, J., Fukuda, M.
(2004). Induction of peripheral lymph node addressin in human gastric mucosa infected by Helicobacter pylori. Proc. Natl. Acad. Sci. USA
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(2004). Allele 2 of the Interleukin-1 Receptor Antagonist Gene Is Associated With Early Gastric Cancer. JCO
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Takenaka, R., Yokota, K., Ayada, K., Mizuno, M., Zhao, Y., Fujinami, Y., Lin, S.-N., Toyokawa, T., Okada, H., Shiratori, Y., Oguma, K.
(2004). Helicobacter pylori heat-shock protein 60 induces inflammatory responses through the Toll-like receptor-triggered pathway in cultured human gastric epithelial cells. Microbiology
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Chang, Y. J., Wu, M. S., Lin, J. T., Sheu, B. S., Muta, T., Inoue, H., Chen, C.-C.
(2004). Induction of Cyclooxygenase-2 Overexpression in Human Gastric Epithelial Cells by Helicobacter pylori Involves TLR2/TLR9 and c-Src-Dependent Nuclear Factor-{kappa}B Activation. Mol. Pharmacol.
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Wang, K.-Y., Li, S.-N., Liu, C.-S., Perng, D.-S., Su, Y.-C., Wu, D.-C., Jan, C.-M., Lai, C.-H., Wang, T.-N., Wang, W.-M.
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Nyan, D. C., Welch, A. R., Dubois, A., Coleman, W. G. Jr.
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(2004). Helicobacter pylori Infection of Human and Murine Primary Gastric Cells. Infect. Immun.
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(2004). Biochemical Characterization of Protein Complexes from the Helicobacter pylori Protein Interaction Map: Strategies for Complex Formation and Evidence for Novel Interactions Within Type IV Secretion Systems. Mol. Cell. Proteomics
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Biarc, J., Nguyen, I. S., Pini, A., Gosse, F., Richert, S., Thierse, D., Van Dorsselaer, A., Leize-Wagner, E., Raul, F., Klein, J.-P., Scholler-Guinard, M.
(2004). Carcinogenic properties of proteins with pro-inflammatory activity from Streptococcus infantarius (formerly S.bovis). Carcinogenesis
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de Paulis, A., Prevete, N., Fiorentino, I., Walls, A. F., Curto, M., Petraroli, A., Castaldo, V., Ceppa, P., Fiocca, R., Marone, G.
(2004). Basophils Infiltrate Human Gastric Mucosa at Sites of Helicobacter pylori Infection, and Exhibit Chemotaxis in Response to H. pylori-derived Peptide Hp(2-20). J. Immunol.
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Abdel-Latif, M. M. M., Windle, H. J., Fitzgerald, K. A., Ang, Y. S., Eidhin, D. N., Li-Weber, M., Sabra, K., Kelleher, D.
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Campbell, D. I., Pearce, M. S., Parker, L., Thomas, J. E., Sullivan, P. B., Dale, A.
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Jaffe, E. S.
(2004). Common Threads of Mucosa-Associated Lymphoid Tissue Lymphoma Pathogenesis: From Infection to Translocation. JNCI J Natl Cancer Inst
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