Nan Hu1, Zhaoming Wang1, Xin Song2, Lixuan Wei3, Byung Sik Kim4, Neal D Freedman1, Jiwon Baek5, Laurie Burdette6, Jiang Chang3, Charles Chung6, Sanford M Dawsey1, Ti Ding7, Yu-Tang Gao8, Carol Giffen9, Yaling Han3, Myunghee Hong5, Jia Huang2, Hee Sung Kim4, Woon-Puay Koh10, Linda M Liao1, Yi Min Mao2, You-Lin Qiao11, Xiao-Ou Shu12, Wen Tan3, Chaoyu Wang1, Chen Wu3, Min-Jie Wu13, Yong-Bing Xiang8, Meredith Yeager6, Jeong Hwan Yook4, Jian-Min Yuan14, Peng Zhang2, Xue-Ke Zhao2, Wei Zheng12, Kyuyoung Song5, Li-Dong Wang2, Dongxin Lin3, Stephen J Chanock1, Alisa M Goldstein1, Philip R Taylor1, Christian C Abnet1. 1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. 2. Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, People's Republic of China. 3. Department of Etiology & Carcinogenesis, Cancer Institute and Hospital Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China. 4. Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. 5. Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, South Korea. 6. 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. 7. Shanxi Cancer Hospital, Taiyuan, Shanxi, People's Republic of China. 8. Shanghai Cancer Institute, Shanghai, People's Republic of China. 9. Information Management Services Inc., Silver Spring, Maryland, USA. 10. Duke-NUS Graduate Medical School Singapore, Singapore, Singapore. 11. Department of Epidemiology, Cancer Institute and Hospital Chinese Academy of Medical Sciences, Beijing, People's Republic of China. 12. Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee, USA. 13. Cancer Research Center, Xinxiang Medical University, Xinxiang, Henan, People's Republic of China. 14. University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA.
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Authors: Julia Mayerle; Caroline M den Hoed; Claudia Schurmann; Lisette Stolk; Georg Homuth; Marjolein J Peters; Lisette G Capelle; Kathrin Zimmermann; Fernando Rivadeneira; Sybille Gruska; Henry Völzke; Annemarie C de Vries; Uwe Völker; Alexander Teumer; Joyce B J van Meurs; Ivo Steinmetz; Matthias Nauck; Florian Ernst; Frank-Ulrich Weiss; Albert Hofman; Martin Zenker; Heyo K Kroemer; Holger Prokisch; Andre G Uitterlinden; Markus M Lerch; Ernst J Kuipers; Ernst Kuipers Journal: JAMA Date: 2013-05-08 Impact factor: 56.272
Authors: Christian C Abnet; Neal D Freedman; Albert R Hollenbeck; Joseph F Fraumeni; Michael Leitzmann; Arthur Schatzkin Journal: Eur J Cancer Date: 2008-01-24 Impact factor: 9.162
Authors: Christian C Abnet; Neal D Freedman; Nan Hu; Zhaoming Wang; Kai Yu; Xiao-Ou Shu; Jian-Min Yuan; Wei Zheng; Sanford M Dawsey; Linda M Dong; Maxwell P Lee; Ti Ding; You-Lin Qiao; Yu-Tang Gao; Woon-Puay Koh; Yong-Bing Xiang; Ze-Zhong Tang; Jin-Hu Fan; Chaoyu Wang; William Wheeler; Mitchell H Gail; Meredith Yeager; Jeff Yuenger; Amy Hutchinson; Kevin B Jacobs; Carol A Giffen; Laurie Burdett; Joseph F Fraumeni; Margaret A Tucker; Wong-Ho Chow; Alisa M Goldstein; Stephen J Chanock; Philip R Taylor Journal: Nat Genet Date: 2010-08-22 Impact factor: 38.330
Authors: F Kamangar; Y-L Qiao; M J Blaser; X-D Sun; H Katki; J-H Fan; G I Perez-Perez; C C Abnet; P Zhao; S D Mark; P R Taylor; S M Dawsey Journal: Br J Cancer Date: 2006-12-19 Impact factor: 7.640