Interaction of Cyclooxygenase-2 promoter polymorphisms with Helicobacter pylori infection and risk of gastric cancer

Overexpression of cyclooxygenase (COX)‐2 has been implicated in the development of cancer. This study aimed to evaluate the relationship between genetic variants in COX‐2 promoter interacting with Helicobacter pylori and the susceptibility to gastric cancer (GC). Three COX‐2 polymorphisms −1290A>G (rs689465), −1195G>A (rs689466), and −765G>C (rs20417) were genotyped in 323 GC patients and 944 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression model. In GC patients, the ORs were 2.33 (95% CI = 1.50–3.63) and 2.70 (95% CI = 1.68–4.33) for −1195AA and −765CG genotype carriers, respectively. Haplotype analysis showed all −1195A allele‐containing haplotypes, except G−1290–A−1195–G−765, were associated with increased risk for GC, compared with the A−1290–G−1195–G−765 haplotype. Moreover, significant multiplicative and additive interactions were observed between H. pylori infection and all these three polymorphisms, and H. pylori‐infected subjects carrying the variant allele of −1290A>G, −1195G>A, or −765G>C had increased risk of GC compared with non‐H. pylori‐infected subjects with wild‐type allele (OR = 4.10, 95% CI = 1.90–8.83; OR = 3.46, 95% CI = 1.31–9.11; and OR = 3.32, 95% = 1.27–8.73, respectively). Our results suggested that the COX‐2 promoter polymorphisms were associated with increased risk of GC, especially interacting with H. pylori infection. © 2011 Wiley Periodicals, Inc.