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

Nat Genet. 2010 Sep;42(9):764-7. doi: 10.1038/ng.649. Epub 2010 Aug 22.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adenocarcinoma / ethnology
  • Adenocarcinoma / genetics*
  • Asian Continental Ancestry Group / genetics
  • Carcinoma, Squamous Cell / ethnology
  • Carcinoma, Squamous Cell / genetics*
  • Case-Control Studies
  • Chromosomes, Human, Pair 10*
  • Esophageal Neoplasms / ethnology
  • Esophageal Neoplasms / genetics*
  • Female
  • Gene Frequency
  • Genetic Loci*
  • Genetic Predisposition to Disease / genetics
  • Genome-Wide Association Study
  • Humans
  • Linkage Disequilibrium
  • Male
  • Phosphoinositide Phospholipase C / genetics*
  • Stomach Neoplasms / ethnology
  • Stomach Neoplasms / genetics*

Substances

  • Phosphoinositide Phospholipase C
  • phospholipase C epsilon