title: Additive interactions between PRKAA1 polymorphisms and Helicobacter pylori CagA infection associated with gastric cancer risk in Koreans.
abstract: 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.
authors.affiliation: Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University, Cheongju, Korea.
authors.forename: Sang-Yong
authors.initials: SY
authors.lastname: Eom
authors.affiliation: Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University, Cheongju, Korea.
authors.forename: Seon-Mi
authors.initials: SM
authors.lastname: Hong
authors.affiliation: Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University, Cheongju, Korea.
authors.forename: Dong-Hyuk
authors.initials: DH
authors.lastname: Yim
authors.affiliation: Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University, Cheongju, Korea.
authors.forename: Hyo-Jin
authors.initials: HJ
authors.lastname: Kwon
authors.affiliation: Department of Surgery, College of Medicine, Chungbuk National University, Cheongju, Korea.
authors.forename: Dae-Hoon
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Surgery, College of Medicine, Chungbuk National University, Cheongju, Korea.
authors.forename: Hyo-Yung
authors.initials: HY
authors.lastname: Yun
authors.affiliation: Department of Surgery, College of Medicine, Chungbuk National University, Cheongju, Korea.
authors.forename: Young-Jin
authors.initials: YJ
authors.lastname: Song
authors.affiliation: Department of Internal Medicine, College of Medicine, Chungbuk National University, Cheongju, Korea.
authors.forename: Sei-Jin
authors.initials: SJ
authors.lastname: Youn
authors.affiliation: Department of Food and Nutrition, Chungbuk National University, Cheongju, Korea.
authors.forename: Taisun
authors.initials: T
authors.lastname: Hyun
authors.affiliation: Department of Surgery, College of Medicine, Eulji University, Daejon, Korea.
authors.forename: Joo-Seung
authors.initials: JS
authors.lastname: Park
authors.affiliation: Department of Surgery, Asan Medical Center, College of Medicine, Ulsan University, Seoul, Korea.
authors.forename: Byung Sik
authors.initials: BS
authors.lastname: Kim
authors.affiliation: Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University, Cheongju, Korea.
authors.forename: Yong-Dae
authors.initials: YD
authors.lastname: Kim
authors.affiliation: Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University, Cheongju, Korea.
authors.forename: Heon
authors.initials: H
authors.lastname: Kim
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics*; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D005838:Genotype; D016481:Helicobacter Infections / Q000150:complications* / Q000382:microbiology; D016480:Helicobacter pylori; D006801:Humans; D008297:Male; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D056910:Republic of Korea / Q000453:epidemiology; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000453:epidemiology* / Q000209:etiology*
chemical_list: D055372:AMP-Activated Protein Kinases; C526180:PRKAA1 protein, human
keywords: 
  Helicobacter pylori
  ; AMP-activated protein kinase; gastric cancer; gene-environment interaction