Association of Single Nucleotide Polymorphisms in the Prostaglandin-endoperoxide Synthase 2 (PTGS2) and Phospholipase A2 Group IIA (PLA2G2A) Genes with Susceptibility to Esophageal Squamous Cell Carcinoma

Abstract

<b>Background:</b> The prostaglandin-endoperoxide synthase 2 (PTGS2) and phospholipase A2 group IIA (PLA2G2A)genes encode enzymes that are involved in arachidonic acid and prostaglandin biosynthesis. Dysregulation ofboth genes is associated with inflammation and carcinogenesis, including esophageal squamous cell carcinoma(ESCC). We therefore hypothesized that there is an association between single nucleotide polymorphisms (SNPs)in these genes and susceptibility to ESCC. <br/><b>Methods</b>: We performed a gene-wide tag SNP-based associationstudy to examine the association of SNPs in PTGS2 and PLA2G2A with ESCC in 269 patients and 269 healthycontrols from Taihangshan Mountain, Henan and Hebei Provinces, the rural area of China which has the highestincidence of esophageal cancer in the world. Thirteen tag SNPs in PLA2G2A and 4 functional SNPs in PTGS2were selected and genotyped using a high-throughput Mass Array genotyping platform. <br/><b>Results</b>: We found amodest increased risk of ESCC in subjects with the PTGS2 rs12042763 AA genotype (OR=1.23; 95% CI, 1.00-3.04) compared with genotype GG. For PLA2G2A, a decreased risk of ESCC was observed in subjects withthe rs11677 CT (OR=0.51, 95%CI, 0.29-0.85) or TT genotype (OR=0.51, 95%CI, 0.17-0.96) or the T carriers(CT+TT) (OR=0.52, 95%CI, 0.31-0.85) when compared with the CC genotype. Also for PLA2G2A, rs2236771C allele carriers were more frequent in the control group (P=0.02). Subjects with the GC (OR=0.55, 95%CI,0.33-0.93) or CC genotype (OR=0.38, 95% CI, 0.16-0.94) or the C carriers (GC+CC) (OR=0.52, 95%CI, 0.32-0.85) showed a negative association with ESCC susceptibility. <br/><b>Conclusions</b>: Our results suggest that PTGS2 andPLA2G2A gene polymorphisms may modify the risk of ESCC development.