Additive interactions between PRKAA1 polymorphisms and Helicobacter pylori CagA infection associated with gastric cancer risk in Koreans

作者：Eom Sang Yong; Hong Seon Mi; Yim Dong Hyuk; Kwon Hyo Jin; Kim Dae Hoon; Yun Hyo Yung; Song Young Jin; Youn Sei Jin; Hyun Taisun; Park Joo Seung; Kim Byung Sik; Kim Yong Dae; Kim Heon

来源：Cancer Medicine, 2016, 5(11): 3326-3335.

DOI：10.1002/cam4.926

• AMP-activated protein kinase
• gastric cancer
• gene-environment interaction
• Helicobacter pylori

Although several studies reported genetic polymorphisms in protein kinase AMP-activated alpha 1 catalytic subunit (PRKAA1) and their associations with gastric cancer risk, few have evaluated associations between Helicobacter pylori infection and PRKAA1 gene-environment interactions. Here, we evaluated the effects of interactions between H. pylori infection and PRKAA1 polymorphisms on gastric cancer risk in Koreans. In this hospital-based case-control study, PRKAA1 genotypes were analyzed and H. pylori infection and CagA status were examined using a serologic method in 846 pairs of gastric cancer patients and controls matched for age and sex. H. pylori seropositivity was associated with a 1.43-fold [95% confidence interval: 1.12-1.81] increase in the risk of gastric cancer, and CagA low-positive titers during H. pylori infection increased the risk by 1.85-fold (95% confidence interval, 1.38-2.48). Significant positive interaction between the PRKAA1 rs13361707 genotype and H. pylori infection was verified on an additive scale [relative excess risk due to interaction, 0.55; 95% confidence interval, 0.05-1.04; P = 0.030], and the gene-environment interaction between PRKAA1 rs13361707 and CagA status was also statistically significant (relative excess risk due to interaction, 0.50; 95% confidence interval, 0.30-0.70; P < 0.001). Our results indicated that H. pylori infection, CagA status, and PRKAA1 polymorphisms were risk factors for gastric cancer in Koreans, and that the combination of two of these factors rather than their independent effects synergistically increased the risk.

• 出版日期2016-11