Genome-wide association analyses of esophageal squamous cell carcinoma in Chinese identify multiple susceptibility loci and gene-environment interactions

Abstract

We conducted a genome-wide association study of gastric cancer (GC) and esophageal squamous cell carcinoma (ESCC) in ethnic Chinese subjects in which we genotyped 551,152 single nucleotide polymorphisms (SNPs). We report a combined analysis of 2,240 GC 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 GC and ESCC independently. A notable signal was rs2274223, a nonsynonymous SNP located in PLCE1, for GC (P=8.40×1010Information Management Services Inc.Silver SpringMarylandUNITED STATES; per allele odds ratio (OR) = 1.31) and ESCC (P=3.85×10−9; OR = 1.34). The association with GC differed by anatomic subsite. For tumors located in the cardia the association was stronger (P=4.19 × 10−15; OR= 1.57) and for those located in the noncardia stomach it was absent (P=0.44; OR=1.05). Our findings at 10q23 could provide insight into the high incidence rates of both cancers in China.

Epidemiology of esophageal cancer

“…They confirmed the known association of the ALDH2 locus on 12q24 to ESCC, and a joint analysis showed that drinkers with both of the ADH1B and ALDH2 risk alleles had a fourfold increased risk for ESCC compared to drinkers without these risk alleles. Their results underscore the direct genetic contribution to ESCC risk, as well as the genetic contribution to ESCC through interaction with alcohol consumption [55] . There are also some studies on polymorphism on other locations for esophageal adenocarcinoma with smaller samples.…”

“…The genome-wide association studies (GWAS) has emerged as a powerful and successful tool to identify common disease alleles by using high-throughput genotyping technology to interrogate a large number of tagging single nucleotide polymorphisms (SNPs) that serve as surrogates for untested common SNPs across the genome. So far, GWAS of esophageal cancers including ESCC in individuals of European and Japanese ancestry, have shown that variants in ADH genes and/or ALDH2 are associated with risk of ESCC [55][56][57][58] . More recently, Wu et al further reported that nine new ESCC susceptibility loci, of which seven, at chromosomes 4q23, 16q12.1, 17q21, 22q12, 3q27, 17p13 and 18p11, had a significant marginal effect (P = 1.78 × 10 -39 to P = 2.49 × 10 -11 ) and two of which, at 2q22 and 13q33, had a significant association only in the gene-alcohol drinking interaction [gene-environment interaction P (PG × E) = 4.39 × 10 -11 and PG × E = 4.80 × 10 -8…”

Down‐regulation of 5S rRNA by miR‐150 and miR‐383 enhances c‐Myc–rpL11 interaction and inhibits proliferation of esophageal squamous carcinoma cells

“…Cigarette smoking, heavy alcoholic consumption, micro-nutrient deficiency as well as dietary carcinogen exposure have been identified as main environmental etiological factors of ESCC [1][2][3]. However, only a part of exposed individuals eventually developed ESCC, indicating that host genetic differences may also contribute to ESCC carcinogenesis [4][5][6].…”

Silencing of Long Noncoding RNA MALAT1 by miR-101 and miR-217 Inhibits Proliferation, Migration, and Invasion of Esophageal Squamous Cell Carcinoma Cells

“…Epidemiological evidences indicate that heavy alcohol drinking, tobacco smoking, micronutrient deficiency, and dietary carcinogen exposure are major environmental risk factors of this fatal disease (2,3). However, only a part of exposed individuals eventually develop ESCC, demonstrating that host genetic components may also contribute to ESCC etiology (2)(3)(4)(5)(6)(7).…”