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Helicobacter pylori seropositivities and risk of pancreatic carcinoma
Harvey A Risch1, Lingeng Lu, Mark S Kidd
1Authors' Affiliations: Department of Chronic Disease Epidemiology, Yale School of Public Health; Department of Surgery, Yale School of Medicine, New Haven, Connecticut; Department of Epidemiology, Shanghai Cancer Institute, Jiao Tong University; Department of Pancreas and Hepatobiliary Surgery, Shanghai Medical College, Fudan University, Shanghai, China; and Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii.
Background:
Pathophysiologic actions of Helicobacter pylori colonization on gastric acidity have been hypothesized to modulate the effect of pancreatic carcinogens, through CagA-negative organism strain type, hyperchlorhydria and increased risk of pancreatic cancer, or CagA-positive strain, hypochlorhydria and decreased risk of pancreatic cancer. We aimed to determine H. pylori strain-specific associations with pancreatic cancer in a population in which colonization by CagA-positive strains is common.
Methods:
We carried out a large population-based case-control study of pancreatic carcinoma in Shanghai, China. Venipuncture specimens were obtained from a representative sample of 761 case patients and 794 randomly selected control subjects matched by category of age and gender. Antibody seropositivity for H. pylori and its virulence protein CagA were determined by commercial enzyme-linked immunosorbent IgG assays.
Results:
Compared with individuals seronegative for both H. pylori and CagA, decreased pancreas-cancer risk was seen for CagA seropositivity [adjusted OR, 0.68; 95% confidence interval (CI), 0.54-0.84], whereas some increased risk was suggested for CagA-negative H. pylori seropositivity (OR, 1.28; 95% CI, 0.76-2.13). No risk interactions were observed between CagA seropositivity and gender, cigarette smoking, or age-21 body mass index.
Conclusions:
Similar to what has been seen in animal models, our results provide suggestive evidence in humans for the involvement of gastric acidity, through its bidirectional modification according to colonization by H. pylori CagA strain type, in the risk of pancreatic carcinoma.
Impact:
H. pylori colonization may have diverse effects on cancer risk, depending on the organism strain type as well as on the particular cancer site.
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