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Genome-wide association study of gastric adenocarcinoma in Asia: a comparison of associations between cardia and non-cardia tumours
  1. Nan Hu1,
  2. Zhaoming Wang1,
  3. Xin Song2,
  4. Lixuan Wei3,
  5. Byung Sik Kim4,
  6. Neal D Freedman1,
  7. Jiwon Baek5,
  8. Laurie Burdette1,6,
  9. Jiang Chang3,
  10. Charles Chung1,6,
  11. Sanford M Dawsey1,
  12. Ti Ding7,
  13. Yu-Tang Gao8,
  14. Carol Giffen9,
  15. Yaling Han3,
  16. Myunghee Hong5,
  17. Jia Huang2,
  18. Hee Sung Kim4,
  19. Woon-Puay Koh10,
  20. Linda M Liao1,
  21. Yi Min Mao2,
  22. You-Lin Qiao11,
  23. Xiao-Ou Shu12,
  24. Wen Tan3,
  25. Chaoyu Wang1,
  26. Chen Wu3,
  27. Min-Jie Wu13,
  28. Yong-Bing Xiang8,
  29. Meredith Yeager1,6,
  30. Jeong Hwan Yook4,
  31. Jian-Min Yuan14,
  32. Peng Zhang2,
  33. Xue-Ke Zhao2,
  34. Wei Zheng12,
  35. Kyuyoung Song5,
  36. Li-Dong Wang2,
  37. Dongxin Lin3,
  38. Stephen J Chanock1,
  39. Alisa M Goldstein1,
  40. Philip R Taylor1,
  41. Christian C Abnet1
  1. 1Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
  2. 2Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, People's Republic of China
  3. 3Department of Etiology & Carcinogenesis, Cancer Institute and Hospital Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
  4. 4Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
  5. 5Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, South Korea
  6. 6Cancer Genome Research Laboratory, Division of Cancer Epidemiology and Genetics, Advanced Technology Program, SAIC-Frederick Inc., NCI-Frederick, Frederick, Maryland, USA
  7. 7Shanxi Cancer Hospital, Taiyuan, Shanxi, People's Republic of China
  8. 8Shanghai Cancer Institute, Shanghai, People's Republic of China
  9. 9Information Management Services Inc., Silver Spring, Maryland, USA
  10. 10Duke-NUS Graduate Medical School Singapore, Singapore, Singapore
  11. 11Department of Epidemiology, Cancer Institute and Hospital Chinese Academy of Medical Sciences, Beijing, People's Republic of China
  12. 12Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee, USA
  13. 13Cancer Research Center, Xinxiang Medical University, Xinxiang, Henan, People's Republic of China
  14. 14University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA
  1. Correspondence to Dr Christian Abnet, Division of Cancer Epidemiology and Genetics, Nutritional Epidemiology Branch, National Cancer Institute, 9609 Medical Center Dr Rm 6e430 MSC 9768, Bethesda, MD 20892, USA; abnet{at}nih.gov

Abstract

Objective 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.

Design 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.

Results 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.

Conclusions Our results suggest that associations for SNPs with gastric cancer show some different results by tumour location in the stomach.

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