title: Genome-wide association study of gastric adenocarcinoma in Asia: a comparison of associations between cardia and non-cardia tumours.
abstract: Genome-wide association studies (GWAS) of gastric cancer have reported differences in single-nucleotide polymorphism (SNP) associations for tumour subtypes, particularly when divided by location into the gastric cardia versus the non-cardia.
  
  
  
  Here we present results for a GWAS using 2350 East Asian gastric cancer cases divided as 1189 gastric cardia and 1027 gastric non-cardia cases and 2708 controls. We also included up to 3042 cardia cases, 4359 non-cardia cases and 7548 controls for replication from two Chinese studies and one Korean study. From the GWAS, we selected 12 top SNPs for each gastric cancer subtype, 4 top SNPs for total gastric cancer and 1 SNP in MUC1 for replication testing.
  
  
  
  We observed genome-wide significant associations for rs10074991 in PRKAA1 at 5p13.1 for cardia (p=7.36×10(-12)) and non-cardia cancers (p=2.42×10(-23)) with per allele OR (95% CI) for the combined endpoint of 0.80 (0.77 to 0.83). At 6p21.1, rs2294693 near UNC5CL was significantly associated with gastric non-cardia cancer risk (p=2.50×10(-8)), with OR (95% CI) of 1.18 (1.12 to 1.26), but there was only a nominal association for cardia cancer (p=1.47×10(-2)). We also confirmed a previously reported association for rs4072037 in MUC1 with p=6.59×10(-8) for total gastric cancer and similar estimates for cardia and non-cardia cancers. Three SNPs in PSCA previously reported to be associated with gastric non-cardia cancer showed no apparent association for cardia cancer.
  
  
  
  Our results suggest that associations for SNPs with gastric cancer show some different results by tumour location in the stomach.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Nan
authors.initials: N
authors.lastname: Hu
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Zhaoming
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Song
authors.affiliation: Department of Etiology & Carcinogenesis, Cancer Institute and Hospital Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Lixuan
authors.initials: L
authors.lastname: Wei
authors.affiliation: Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: Byung Sik
authors.initials: BS
authors.lastname: Kim
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Neal D
authors.initials: ND
authors.lastname: Freedman
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: Jiwon
authors.initials: J
authors.lastname: Baek
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA Cancer Genome Research Laboratory, Division of Cancer Epidemiology and Genetics, Advanced Technology Program, SAIC-Frederick Inc., NCI-Frederick, Frederick, Maryland, USA.
authors.forename: Laurie
authors.initials: L
authors.lastname: Burdette
authors.affiliation: Department of Etiology & Carcinogenesis, Cancer Institute and Hospital Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Chang
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA Cancer Genome Research Laboratory, Division of Cancer Epidemiology and Genetics, Advanced Technology Program, SAIC-Frederick Inc., NCI-Frederick, Frederick, Maryland, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Chung
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Sanford M
authors.initials: SM
authors.lastname: Dawsey
authors.affiliation: Shanxi Cancer Hospital, Taiyuan, Shanxi, People's Republic of China.
authors.forename: Ti
authors.initials: T
authors.lastname: Ding
authors.affiliation: Shanghai Cancer Institute, Shanghai, People's Republic of China.
authors.forename: Yu-Tang
authors.initials: YT
authors.lastname: Gao
authors.affiliation: Information Management Services Inc., Silver Spring, Maryland, USA.
authors.forename: Carol
authors.initials: C
authors.lastname: Giffen
authors.affiliation: Department of Etiology & Carcinogenesis, Cancer Institute and Hospital Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Yaling
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: Myunghee
authors.initials: M
authors.lastname: Hong
authors.affiliation: Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, People's Republic of China.
authors.forename: Jia
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: Hee Sung
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Duke-NUS Graduate Medical School Singapore, Singapore, Singapore.
authors.forename: Woon-Puay
authors.initials: WP
authors.lastname: Koh
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Linda M
authors.initials: LM
authors.lastname: Liao
authors.affiliation: Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, People's Republic of China.
authors.forename: Yi Min
authors.initials: YM
authors.lastname: Mao
authors.affiliation: Department of Epidemiology, Cancer Institute and Hospital Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
authors.forename: You-Lin
authors.initials: YL
authors.lastname: Qiao
authors.affiliation: Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Xiao-Ou
authors.initials: XO
authors.lastname: Shu
authors.affiliation: Department of Etiology & Carcinogenesis, Cancer Institute and Hospital Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Wen
authors.initials: W
authors.lastname: Tan
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Chaoyu
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Etiology & Carcinogenesis, Cancer Institute and Hospital Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wu
authors.affiliation: Cancer Research Center, Xinxiang Medical University, Xinxiang, Henan, People's Republic of China.
authors.forename: Min-Jie
authors.initials: MJ
authors.lastname: Wu
authors.affiliation: Shanghai Cancer Institute, Shanghai, People's Republic of China.
authors.forename: Yong-Bing
authors.initials: YB
authors.lastname: Xiang
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA Cancer Genome Research Laboratory, Division of Cancer Epidemiology and Genetics, Advanced Technology Program, SAIC-Frederick Inc., NCI-Frederick, Frederick, Maryland, USA.
authors.forename: Meredith
authors.initials: M
authors.lastname: Yeager
authors.affiliation: Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: Jeong Hwan
authors.initials: JH
authors.lastname: Yook
authors.affiliation: University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA.
authors.forename: Jian-Min
authors.initials: JM
authors.lastname: Yuan
authors.affiliation: Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, People's Republic of China.
authors.forename: Xue-Ke
authors.initials: XK
authors.lastname: Zhao
authors.affiliation: Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: Kyuyoung
authors.initials: K
authors.lastname: Song
authors.affiliation: Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, People's Republic of China.
authors.forename: Li-Dong
authors.initials: LD
authors.lastname: Wang
authors.affiliation: Department of Etiology & Carcinogenesis, Cancer Institute and Hospital Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Dongxin
authors.initials: D
authors.lastname: Lin
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Alisa M
authors.initials: AM
authors.lastname: Goldstein
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Philip R
authors.initials: PR
authors.lastname: Taylor
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Christian C
authors.initials: CC
authors.lastname: Abnet
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics*; D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D044466:Asian People; D002299:Cardia; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D018396:Mucin-1 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea / Q000453:epidemiology; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000473:pathology
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C060192:MUC1 protein, human; D018396:Mucin-1; C486467:UNC5CL protein, human; D055372:AMP-Activated Protein Kinases; C526180:PRKAA1 protein, human