A shared susceptibility locus in PLCE1 at 10q23 for gastric adenocarcinoma and esophageal squamous cell carcinoma

• Published in: Nature genetics Vol. 42; no. 9; pp. 764 - 767
• Main Authors: Abnet, Christian C, Freedman, Neal D, Hu, Nan, Wang, Zhaoming, Yu, Kai, Shu, Xiao-Ou, Yuan, Jian-Min, Zheng, Wei, Dawsey, Sanford M, Dong, Linda M, Lee, Maxwell P, Ding, Ti, Qiao, You-Lin, Gao, Yu-Tang, Koh, Woon-Puay, Xiang, Yong-Bing, Tang, Ze-Zhong, Fan, Jin-Hu, Wang, Chaoyu, Wheeler, William, Gail, Mitchell H, Yeager, Meredith, Yuenger, Jeff, Hutchinson, Amy, Jacobs, Kevin B, Giffen, Carol A, Burdett, Laurie, Fraumeni, Joseph F, Tucker, Margaret A, Chow, Wong-Ho, Goldstein, Alisa M, Chanock, Stephen J, Taylor, Philip R
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.09.2010; Nature Publishing Group
• Subjects: 631/208/727/2000; 631/67/1504/1477; 631/67/1504/1829; Adenocarcinoma - ethnology; Adenocarcinoma - genetics; Agriculture; Analysis; Animal Genetics and Genomics; Asian People - genetics; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Carcinoma, Squamous Cell - ethnology; Carcinoma, Squamous Cell - genetics; Case-Control Studies; Chromosomes, Human, Pair 10; Classical genetics, quantitative genetics, hybrids; Diagnosis; Disease susceptibility; Esophageal cancer; Esophageal Neoplasms - ethnology; Esophageal Neoplasms - genetics; Esophagus; Female; Fundamental and applied biological sciences. Psychology; Gastroenterology. Liver. Pancreas. Abdomen; Gene Frequency; Gene Function; Genetic aspects; Genetic Loci; Genetic Predisposition to Disease - genetics; Genetics of eukaryotes. Biological and molecular evolution; Genome-Wide Association Study; Human Genetics; Humans; letter; Linkage Disequilibrium; Male; Medical sciences; Methods, theories and miscellaneous; Phosphoinositide Phospholipase C - genetics; Risk factors; Stomach cancer; Stomach Neoplasms - ethnology; Stomach Neoplasms - genetics; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; China; Genetic mapping; Sensitivity; Susceptibility locus; Esophageal disease; Esophagus squamous cell carcinoma; Digestive diseases; Malignant tumor; Stomach adenocarcinoma; Stomach cancer; Cancer; Gastric disease
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.649

Christian Abnet and colleagues report genome-wide association studies for gastric adenocarcinoma and esophageal squamous cell carcinoma in a Chinese population. They identified a new shared risk locus in the PLCE1 gene at 10q23. We conducted a genome-wide association study of gastric cancer and esophageal squamous cell carcinoma (ESCC) in ethnic Chinese subjects in which we genotyped 551,152 SNPs. We report a combined analysis of 2,240 gastric cancer cases, 2,115 ESCC cases and 3,302 controls drawn from five studies. In logistic regression models adjusted for age, sex and study, multiple variants at 10q23 had genome-wide significance for gastric cancer and ESCC independently. A notable signal was rs2274223, a nonsynonymous SNP located in PLCE1 , for gastric cancer ( P = 8.40 × 10 −9 ; per-allele odds ratio (OR) = 1.31) and ESCC ( P = 3.85 × 10 −9 ; OR = 1.34). The association with gastric cancer differed by anatomic subsite. For tumors in the cardia the association was stronger ( P = 4.19 × 10 −15 ; OR = 1.57), and for those in the noncardia stomach it was absent ( P = 0.44; OR = 1.05). Our findings at 10q23 could provide insight into the high incidence of both cancers in China.