title: Environmental factors, seven GWAS-identified susceptibility loci, and risk of gastric cancer and its precursors in a Chinese population.
abstract: Gene-environment interactions may increase gastric cancer (GC) risk. Seven susceptibility loci identified by genome-wide association studies (GWASs) suggest that genetic factors play a role in gastric carcinogenesis. Meanwhile, Helicobacter pylori (H. pylori) infection, smoking, and alcohol drinking are also important environmental factors for gastric cancer. However, studies to explore the role of gene-environment interactions in gastric carcinogenesis, and particularly the relationship between the seven susceptibility loci and their potential interactions with H. pylori infection, smoking, and alcohol drinking in risk of GC, and severe intestinal metaplasia (IM)/dysplasia, have been inconclusive. A total of 1273 subjects in a Chinese population were recruited, and genotyping was carried out using the competitive allele-specific PCR (KASP) method. Unconditional logistic regression was applied to model the associations between genetic polymorphisms and the disease risk. Effect modifications by H. pylori infection, smoking and alcohol drinking were evaluated. PSCA rs2294008/rs2976392 showed a significant, multiplicative interaction with H. pylori infection in risk of GC. Meanwhile, PRKAA1 rs13361707 had an additive interaction with H. pylori infection. SLC52A3 rs13042395 showed an interaction with alcohol drinking in risk of GC. Moreover, three SNPs, MUC1 rs4072037, ZBTB20 rs9841504 and PRKAA1 rs13361707, were associated with precancerous gastric lesions (severe IM/dysplasia). Our data suggest that genetic predisposition factors identified by GWAS may interact with environmental risk factors, Particularly for H. pylori infection and alcohol consumption, to increase the risk of GC.
authors.affiliation: State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Cai
authors.affiliation: State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Shuyang
authors.initials: S
authors.lastname: Dai
authors.affiliation: National Office for Cancer Prevention and Control, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Wanqing
authors.initials: W
authors.lastname: Chen
authors.affiliation: National Office for Cancer Prevention and Control, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Changfa
authors.initials: C
authors.lastname: Xia
authors.affiliation: Department of Chronic Disease Epidemiology, Yale School of Public Health, School of Medicine, Yale Cancer Center, Yale University, New Haven, Connecticut, USA.
authors.forename: Lingeng
authors.initials: L
authors.lastname: Lu
authors.affiliation: Center for Disease Control and Prevention of Sheyang County, Sheyang, Jiangsu, China.
authors.forename: Shuguang
authors.initials: S
authors.lastname: Dai
authors.affiliation: Department of Clinical Laboratory, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Qi
authors.affiliation: Department of Clinical Laboratory, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Minjie
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu, China.|Department of Genetic Toxicology, the Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Meilin
authors.initials: M
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Lanping
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Pathology, Feicheng People Hospital, Feicheng, Shandong, China.
authors.forename: Fuhua
authors.initials: F
authors.lastname: Lei
authors.affiliation: National Office for Cancer Prevention and Control, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zuo
authors.affiliation: National Office for Cancer Prevention and Control, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Hongmei
authors.identifier: 0000-0003-3999-3081
authors.initials: H
authors.lastname: Zeng
authors.affiliation: State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Xiaohang
authors.initials: X
authors.lastname: Zhao
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics; D000428:Alcohol Drinking / Q000009:adverse effects* / Q000235:genetics; D000951:Antigens, Neoplasm / Q000235:genetics; D044466:Asian People / Q000235:genetics*; D002681:China; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D016481:Helicobacter Infections / Q000150:complications* / Q000235:genetics; D006801:Humans; D016015:Logistic Models; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics; D018396:Mucin-1 / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects* / Q000235:genetics; D013274:Stomach Neoplasms / Q000209:etiology / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics
chemical_list: D000951:Antigens, Neoplasm; D058851:GPI-Linked Proteins; C060192:MUC1 protein, human; D026901:Membrane Transport Proteins; D018396:Mucin-1; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; C110843:PSCA protein, human; C548553:SLC52A3 protein, human; D014157:Transcription Factors; C427486:ZBTB20 protein, human; D055372:AMP-Activated Protein Kinases; C526180:PRKAA1 protein, human
keywords: 
  Helicobacter pylori
  ; GWAS, gastric cancer; Gene-environment interactions; genetic variant; precancerous lesions