title: Potentially functional variants of PLCE1 identified by GWASs contribute to gastric adenocarcinoma susceptibility in an eastern Chinese population.
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.
  
  
  RESULTS
  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 (P(trend) = 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
  Our results further confirmed that genetic variations in PLCE1 may contribute to gastric adenocarcinoma risk in an eastern Chinese population.
authors.affiliation: Cancer Research Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Mengyun
authors.initials: M
authors.lastname: Wang
authors.forename: Ruoxin
authors.initials: R
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: He
authors.forename: Lixin
authors.initials: L
authors.lastname: Qiu
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.forename: Yanong
authors.initials: Y
authors.lastname: Wang
authors.forename: Menghong
authors.initials: M
authors.lastname: Sun
authors.forename: Yajun
authors.initials: Y
authors.lastname: Yang
authors.forename: Jiucun
authors.initials: J
authors.lastname: Wang
authors.forename: Jingmin
authors.initials: J
authors.lastname: Yang
authors.forename: Ji
authors.initials: J
authors.lastname: Qian
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.forename: Hongxia
authors.initials: H
authors.lastname: Ma
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhou
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002681:China; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D054801:Phosphoinositide Phospholipase C / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D013274:Stomach Neoplasms / Q000235:genetics*
chemical_list: D054801:Phosphoinositide Phospholipase C; C423320:phospholipase C epsilon