Genetic variants in GHR and PLCE1 genes are associated with susceptibility to esophageal cancer

Background: Esophageal cancer (EC) is the leading cause of cancer-related mortality worldwide. The underlying genetic risk factors remain unclear. The association between gene growth hormone receptor (GHR) and phospholipase C epsilon 1 (PLCE1) polymorphisms and the EC risk were identified in this study. Methods: A total of 506 EC cases and 507 controls were included in this research. Two SNPs (rs6898743 ofGHRand rs2274223 ofPLCE1) were selected and genotyped. The associations between gene polymorphisms and the EC risk were assessed by logistic regression analysis. The databases RegulomeDB, GTEx, and UALCAN were used for functional annotations. Results: In the allelic frequencies analysis, the rs6898743 ofGHRwas associated with decreased susceptibility of EC (OR = 0.83, 95% CI: 0.70-1.00,p = 0.049), while rs2274223 ofPLCE1was associated with increased 0.25-fold EC risk (OR = 1.25, 95% CI: 1.02-1.53,p = 0.037). The "GC" genotype of rs6898743 was associated with a 0.24-fold decreased risk of EC under co-dominant model (OR = 0.76, 95% CI: 0.58-0.99,p = 0.046), and the "GA" genotype of rs2274223 was associated with increased EC risk under co-dominant model (OR = 1.36, 95% CI: 1.04-1.77,p = 0.023). Using GTEx database, rs2274223 was found to be significant associated with increasedPLCE1expression (p = 4.1 x 10(-7)) in esophagus muscularis. The UALCAN database demonstrated that theGHRgene was under-expressed in esophageal cancer tissues (p = 0.017). Conclusion: The geneGHRandPLCE1polymorphisms are associated with EC in the general population and the results need to be verified in future.