The Association Between PLCE1Polymorphisms And Genetic Susceptibility To Esophageal Squamous Cell Carcinoma In Henan Han

The esophageal cancer (EC) ranked as the fourth in China. The morbidity and mortality of esophageal cancer are particularly high, and there are about250,000patients newly diagnosed with esophageal cancer each year in China.Furthermore, China has the highest esophageal cancer-specific mortality in the world.Three genome-wide association studies related to esophageal squamous cell carcinoma (ESCC) in Chinese populations have reported that polymorphisms in PLCE1gene showed the association with ESCC. PLCE1protein (Phospholipase C, PLC) initiates a cascade of intracellular responses that result in cell growth, differentiation, apoptosis, and gene expression. PLC is a major signal transduction component through the regulation of various intracellular pathways, including the inositol trisphosphate (IP3) signal transduction pathway.ObjectiveWe hypothesized that the single nucleotide polymorphisms (SNPs) rs10882379G>A, rs3765524C>T and rs829232G>A were associated with the development of ESCC. Single SNP, gene-gene interaction, gene-environment interaction, was analyzed to constitute the theoretical basis for the etiology of esophageal squamous cell carcinoma and control and prevention measures.Methods550newly diagnosed ESCC cases from hospitalwerematched with550healthycontrolsfrom community by age and sex.1,100participants were randomly recruited from central China.SNP rs10882379was differentiated by the PCR-restriction fragment length polymorphism analysis.SNPs rs3765524and rs829232were differentiated by allele-specific PCR analysis.SPSS21.0software package was used for statistical analysis.The difference in factors distributions between cases and controls, and between carriers and non-carriers of the SNPs were tested using χ2-testand unconditional binary logistic regression analysis. Linkage disequilibrium between SNPs was calculated with Haploview4.2. Hardy–Weinberg equilibrium for genotypes in controls was tested by Pearson’s goodness-of-fit χ2-test. Haplotype analyses were conducted with SHEsis on-line software. The χ2-test for trend was performed to analyse the dose-effect association between the number of variant alleles and ESCC. Multifactor dimensionality reduction (MDR) wasemployed to explore gene–gene or gene–environment interaction.Results(1) PLCE1rs10882379SNP was associated with reduced risk of ESCC(allele A vs. G: adjusted OR=0.81,95%CI=0.69-0.97;genotypeGA vs. GG:adjusted OR=0.66,95%CI=0.51-0.86;genotype(GA+AA) vs.GG: adjusted OR=0.67,95%CI=0.53-0.86).(2) PLCE1rs829232SNP was associated with increased risk of ESCC,(allele A vs.G: adjusted OR=1.36,95%CI=1.14-1.63; genotype GA vs. GG: adjusted OR=1.28,95%CI=1.00-1.66; genotype AA vs. GG: adjusted OR=1.37,95%CI=1.12-1.67; genotype (GA+AA) vs. GG: adjusted OR=1.36,95%CI=1.07-1.74).(3) HaplotypeArs10882379Crs3765524Grs829232was significantly associated with decreasing risk of ESCC (adjusted OR=0.74,95%CI=0.61-0.91), while two other haplotypes (Grs10882379Crs3765524Ars829232and Grs10882379Trs3765524Ars829232) were significantly associated with increasing risk of ESCC (haplotype GCA: adjusted OR=1.40,95%CI=1.13-1.73; haplotype GTA: adjusted OR=1.66,95%CI=1.18-2.34).Conclusions(1) PLCE1rs10882379A allelemight be associated with adecreased risk of ESCC. PLCE1rs829232A allele might be associated with an increased risk of ESCC.(2) GCA and GTA haplotypesmight be the risk factors of ESCC. ACG haplotype might be the protective factor of ESCC.