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.

PLCE1 rs2274223 Polymorphism and Susceptibility to Esophageal Cancer: a Meta-analysis

“…But the corresponding pooled ORs were not altered materially e.g. Bye, 2012;Palmer, 2012;Dura, 2012;Gu, 2012;Song, 2012;Duan, 2013 andPiao, 2013 1.30 (1.15, 1.48), P<0.05, suggesting that our results were statistically robust.…”

“…A total of 12 eligible publications (Bye et al, 2012;Dura et al, 2012;Gu et al, 2012;Hu et al, 2012;Palmer et al, 2012;Song et al, 2012;Zhou 2012 (unpublished); Chen et al, 2013;Cui et al, 2013;Duan et al, 2013;Piao et al, 2013; concerning the PLCE1 rs2274223 polymorphisms and 9912 cases and 13023 controls were included in the meta-analysis. The genotype distribution of the controls in all the studies was consistent with HardyWeinberg equilibrium.…”

Prognostic Value of PLCE1 Expression in Upper Gastrointestinal Cancer: a Systematic Review and Meta-analysis

“…A total of 68 abstracts were identified and screened, and 16 studies were reviewed in detail. The studies by Hu et al (2012), Ma et al (2011), Luo et al (2011), Hu et al (2012a, Bye et al (2012), Yuan et al (2011), andGu et al (2012) were excluded because of insufficient clinical information on IHC. The studies of Wang et al (2011) and focused on colorectal cancer.…”

Phospholipase C Epsilon 1 (PLCE1 rs2274223A>G, rs3765524C>T and rs7922612C>T) Polymorphisms and Esophageal Cancer Risk in the Kashmir Valley

“…These findings suggest that single nucleotide polymorphisms (SNPs) in PLCE1 that affect the gene expression or protein functions, may affect the risk of some cancers. However, this finding lacks independent replication in many populations (Bye et al, 2012;Palmer et al, 2012). Therefore, we hypothesized that GWAS discovered SNPs in the PLCE1 gene are may be associated with esophageal cancer risk in patients from Kashmir valley.…”