4.8 Article

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

Journal

NATURE GENETICS
Volume 42, Issue 9, Pages 764-U51

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/ng.649

Keywords

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Funding

  1. National Cancer Institute [SMHS: R01 CA82729, SWHS: R37 CA70837, NO2-CP-11010, SCHS: R01 CA55069, R35 CA53890, R01 CA80205, R01 CA144034, NO2-SC-66211, NO1-SC-91030, HHSN261200477001C]
  2. Shanxi Cancer Hospital and Institute
  3. Cancer Institute of the Chinese Academy of Medical Sciences
  4. NIH, National Cancer Institute
  5. Division of Cancer Epidemiology and Genetics
  6. Center for Cancer Research

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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 x 10(-9); per-allele odds ratio (OR) = 1.31) and ESCC (P = 3.85 x 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 x 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.

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