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

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.

Figure 1. Association results, recombination, and linkage disequilibrium plots for the region of 10q23 with genome-wide significance for gastric cancer (GC) and esophageal squamous cell carcinoma (ESCC)

P-values were derived from 1 df trend tests in logistic regression models adjusted for age, sex, and study and are shown with the LR values for putative recombination hotspots using SequenceLDhot (vertical bars). Pair-wise r² are displayed at the bottom for all SNPs included in the GWAS analysis. Coordinates refer to genome Build 36.1. The figure depicts a region of chromosome 10q23 (95,980,823- 96,174,210) that includes the PLCE1 gene and the different symbols indicate the four different endpoints of total GC, gastric cardia cancers, gastric noncardia cancers, or ESCC.