Potentially Functional Variants of PLCE1 Identified by GWASs Contribute to Gastric Adenocarcinoma Susceptibility in an Eastern Chinese Population

PLoS One

Mengyun Wang¹  Jing He¹  Ruoxin Zhang¹  Yanong Wang²  Jin Li³  Lixin Qiu³  Yajun Yang⁴  Menghong Sun⁵  Jingmin Yang⁶  Li Jin⁶  Qingyi Wei⁶  Ji Qian⁷  Xiaoyan Zhou⁷  Jiucun Wang⁷  Hongxia Ma⁷ 

[1] Cancer Research Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China;Department of Abdominal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China;Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China;Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China;Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China;Fudan-Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China;Ministry of Education Key Laboratory of Contemporary Anthropology, State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China

关键词: Gastric cancer;    Variant genotypes;    Adenocarcinomas;    Alleles;    Cardia;    Haplotypes;    Genome-wide association studies;    Molecular genetics;   

DOI  :  10.1371/journal.pone.0031932

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

Background Recent genome-wide association studies (GWAS) have found a single nucleotide polymorphism (SNP, rs2274223 A>G) in PLCE1 to be associated with risk of gastric adenocarcinoma. In the present study, we validated this finding and also explored the risk associated with another unreported potentially functional SNP (rs11187870 G>C) of PLCE1 in a hospital-based case-control study of 1059 patients with pathologically confirmed gastric adenocarcinoma and 1240 frequency-matched healthy controls. Methodology/Principal Findings We determined genotypes of these two SNPs by the Taqman assay and used logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (95% CI). We found that a significant higher gastric adenocarcinoma risk was associated with rs2274223 variant G allele (adjusted OR = 1.35, 95% CI = 1.14–1.60 for AG+GG vs. AA) and rs11187870 variant C allele (adjusted OR = 1.26, 95% CI = 1.05–1.50 for CG+CC vs. GG). We also found that the number of combined risk alleles (i.e., rs2274223G and rs11187870C) was associated with risk of gastric adenocarcinoma in an allele-dose effect manner (Ptrend = 0.0002). Stratification analysis indicated that the combined effect of rs2274223G and rs11187870C variant alleles was more evident in subgroups of males, non-smokers, non-drinkers and patients with gastric cardia adenocarcinoma. Further real-time PCR results showed that expression levels of PLCE1 mRNA were significantly lower in tumors than in adjacent noncancerous tissues (0.019±0.002 vs. 0.008±0.001, P<0.05). Conclusions/Significances Our results further confirmed that genetic variations in PLCE1 may contribute to gastric adenocarcinoma risk in an eastern Chinese population.

【 授权许可】

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