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- Title
Potentially Functional Variants of PLCE1 Identified by GWASs Contribute to Gastric Adenocarcinoma Susceptibility in an Eastern Chinese Population.
- Authors
Mengyun Wang; Ruoxin Zhang; Jing He; Lixin Qiu; Jin Li; Yanong Wang; Menghong Sun; Yajun Yang; Jiucun Wang; Jingmin Yang; Ji Qian; Li Jin; Hongxia Ma; Qingyi Wei; Xiaoyan Zhou
- Abstract
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.
- Subjects
GENOMES; SINGLE nucleotide polymorphisms; ADENOCARCINOMA; GASTROINTESTINAL cancer; CONFIDENCE intervals; LOGISTIC regression analysis
- Publication
PLoS ONE, 2012, Vol 7, Issue 3, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0031932