title: Multiple polymorphisms within the PLCE1 are associated with esophageal cancer via promoting the gene expression in a Chinese Kazakh population.
abstract: Although recent genome-wide association studies of esophageal squamous cell carcinoma (ESCC) identified a susceptibility locus in phospholipase C epsilon 1 (PLCE1) in Chinese Han populations, few studies further confirmed these findings in pure Kazakh population in which there are higher incidence and mortality of ESCC. Here, we investigated the potential associations between 19 SNPs of PLCE1 and susceptibility to ESCC in 222 cases and 326 controls from a pure ethnic population of Kazakh. Real-time PCR and immunohistochemistry were performed to detect the PLCE1 expression levels and evaluate their association with PLCE1 polymorphism. We found that only 4 SNPs (rs753724, rs11187842, rs2274223, and rs12263737) with moderate linkage disequilibrium (LD) confer significantly increased risk of ESCC, with the ORs ranging from 1.43 to 2.04, and there was a risk allele dose-dependent increase in ESCC risk (P-trend=0.043). Especially, the risk effects of rs2274223 were more evident in poor differentiation and advanced clinical stages of Kazakh ESCC. Additionally, the significantly lowest PLCE1 mRNA expression was found in the KYSE-150 cell line having no risk alleles compared with other three cell lines having risk alleles, and the normal tissues of both homozygous mutant type of PLCE1 rs12263737 and rs2274223 had a higher PLCE1 staining score than that of homozygous wild type. Our findings suggested that genetic variants in PLCE1 might serve as candidate markers for Kazakh ESCC susceptibility, and these LD variants might influence ESCC risk individually and jointly by promoting the messenger RNA and protein expression of the gene.
authors: Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, China; Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi 832002, China.
authors: Xiao-Bin
authors: XB
authors: Cui
authors: Yun-Zhao
authors: YZ
authors: Chen
authors: Xue-Lian
authors: XL
authors: Pang
authors: Wei
authors: W
authors: Liu
authors: Jian-Ming
authors: JM
authors: Hu
authors: Shu-Gang
authors: SG
authors: Li
authors: Lan
authors: L
authors: Yang
authors: Wen-Jie
authors: WJ
authors: Zhang
authors: Chun-Xia
authors: CX
authors: Liu
authors: Yu-Wen
authors: YW
authors: Cao
authors: Jin-Fang
authors: JF
authors: Jiang
authors: Wen-Yi
authors: WY
authors: Gu
authors: James
authors: J
authors: Pang
authors: Lei
authors: L
authors: Yang
authors: Xiang-Lin
authors: XL
authors: Yuan
authors: Shi-Ying
authors: SY
authors: Yu
authors: Feng
authors: F
authors: Li
mesh_terms: D000368:Aged; D000483:Alleles; D002294:Carcinoma, Squamous Cell / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D002460:Cell Line; D002681:China / Q000453:epidemiology; D004938:Esophageal Neoplasms / Q000208:ethnology / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007623:Kazakhstan / Q000208:ethnology; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D054801:Phosphoinositide Phospholipase C / Q000235:genetics*; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000235:genetics; D012306:Risk
chemical_list: D012333:RNA, Messenger; D054801:Phosphoinositide Phospholipase C; C423320:phospholipase C epsilon
keywords: 95% CI; 95% confidence interval; ESCC; Esophageal squamous cell carcinoma; Expression; GWAS; Genome wide association study; IHC; Immunohistochemistry; Kazakh; LD; Linkage disequilibrium; MAF; Minor allele frequency; OR; Odds ratio; PCR; PLCE1; Phospholipase C epsilon 1; Polymerase chain reaction; Polymorphisms; SNPs; Single nucleotide polymorphisms; TNM; Tumor-node-metastasis