Distinct genetic association at the PLCE1 locus with oesophageal squamous cell carcinoma in the South African population.
ABSTRACT Oesophageal squamous cell carcinoma (OSCC) has a high prevalence in the Black and Mixed Ancestry populations of South Africa. Recently, three genome-wide association studies in Chinese populations identified five new OSCC susceptibility loci, including variants at PLCE1, C20orf54, PDE4D, RUNX1 and UNC5CL, but their contribution to disease risk in other populations is unknown. In this study, we report testing variants from these five loci for association with OSCC in the South African Black (407 cases and 849 controls) and Mixed Ancestry (257 cases and 860 controls) populations. The RUNX1 variant rs2014300, which reduced risk in the Chinese population, was associated with an increased risk of OSCC in the Mixed Ancestry population [odds ratio (OR) = 1.33, 95% confidence interval (CI) = 1.09-1.63, P = 0.0055], and none of the five loci were associated in the Black population. Since PLCE1 variants increased the risk of OSCC in all three Chinese studies, this gene was investigated further by sequencing in 46 Black South Africans. This revealed 48 variants, 10 of which resulted in amino acid substitutions, and much lower linkage disequilibrium across the PLCE1 locus than in the Chinese population. We genotyped five PLCE1 variants in cases and controls, and found association of Arg548Leu (rs17417407) with a reduced risk of OSCC (OR = 0.74, 95% CI = 0.60-0.93, P = 0.008) in the Black population. These findings indicate several differences in the genetic contribution to OSCC between the South African and Chinese populations that may be related to differences in their genetic architecture.
- [Show abstract] [Hide abstract]
ABSTRACT: The apoptotic mechanism dysfunction plays a critical role in cancer cell growth and escaping from cancer therapies; the underlying mechanisms are to be further elucidated. This study aims to investigate the role of phospholipase C epsilon 1 (PLCE1) in modulating the apoptosis mechanism in esophageal cancer (Eca) cells. The results showed that Eca cell lines, OE33 and CP-C cells expressed high levels of PLCE1. Knockdown of PLCE1 markedly increased 9.26 folds of the expression of p53 and 13.8 folds of the frequency of apoptotic CP-C cells via modulating the p53 promoter methylation.Cancer Investigation 04/2014; · 2.24 Impact Factor
Dataset: PLCE1 meta-analysis manuscript
- [Show abstract] [Hide abstract]
ABSTRACT: We sought to reassess the association of PLCE1 rs2274223 and susceptibility to esophageal cancer (EC) through a meta-analysis of published case-control studies. Using the PubMed and Embase, we identified nine articles including fourteen case-control studies (15,225 cases and 23,620 controls). ORs and 95 % confidence intervals (CIs) of GG vs. AA, GG + GA vs. AA, GG vs. GA + AA, G vs. A, and AG vs. AA genetic models were estimated for each study. All of the genetic models indicated a statistically significant positive association with EC risk. The association appeared most pronounced for carriers of GG genotype (GG vs. AA: OR, 1.35; 95 % CI, 1.17 to 1.57), and weakest for individuals carrying GA genotype (GA vs. AA: OR, 1.13; 95 % CI, 1.05 to 1.23). Stratification analyses showed similar results in the population of Asians and in esophageal squamous cell carcinoma (ESCC). This meta-analysis provides strong statistical evidence for an elevated risk of EC associated with PLCE1 rs2274223. The association remains significant in Asian population and ESCC. Further investigations are warranted to validate these findings.Tumor Biology 04/2014; · 2.52 Impact Factor