title: MicroRNAs related polymorphisms and genetic susceptibility to esophageal squamous cell carcinoma.
abstract: Esophageal cancer (EC) is the sixth leading cause of cancer-associated death worldwide and the incidence and mortality in China are the highest. The single nucleotide polymorphisms (SNPs) related to microRNAs could lead to alteration in microRNA expression and contribute to the susceptibility of cancer. To evaluate the association between microRNA-related SNPs and EC, a case-control study including 381 patients with esophageal squamous cell carcinoma (ESCC) and 426 gender, age-matched controls was carried out to investigate the genetic susceptibility of five microRNA-related SNPs (rs2910164 in microRNA-146a, rs11614913 in microRNA-196a-2, rs7813 in GEMIN4, rs1595066 and rs16845990 in ErbB4) as well as the interactions of gene-gene and gene-environment in the development of ESCC. Variant homozygote genotype of rs11614913 in microRNA-196a-2 and rs1595066 in ErbB4 were significantly associated with reduced ESCC risk (OR(adjusted): 0.62, 95 % CI: 0.39-0.99 and OR(adjusted): 0.38, 95 % CI: 0.24-0.61). The analysis of haplotypes in ErbB4 gene showed significant increased ESCC risk in G(rs1595066)C(rs16845990) and G(rs1595066)T(rs16845990) haplotypes (OR(adjusted): 1.46, 95 % CI: 1.08-1.99 and OR(adjusted): 1.33, 95 % CI: 1.10-1.62), and inversely reduced ESCC risk in A(rs1595066)C(rs16845990) and A(rs1595066)T(rs16845990) haplotypes with OR (95 % CI) of 0.75 (0.60-0.94) and 0.65 (0.49-0.86), respectively. These findings suggest that the polymorphisms in the microRNA-related genes may affect susceptibility of ESCC in Chinese Han population and the gene-gene interactions play vital roles in the progression on esophageal cancer. Future studies with larger sample and different ethnic populations are required to support and validate our findings.
authors.affiliation: Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, 100 Science Avenue, 450001, Zhengzhou, China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Qu
authors.forename: Honghong
authors.initials: H
authors.lastname: Qu
authors.forename: Manli
authors.initials: M
authors.lastname: Luo
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.forename: Chunhua
authors.initials: C
authors.lastname: Song
authors.forename: Kaijuan
authors.initials: K
authors.lastname: Wang
authors.forename: Jianying
authors.initials: J
authors.lastname: Zhang
authors.forename: Liping
authors.initials: L
authors.lastname: Dai
mesh_terms: D000328:Adult; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D016022:Case-Control Studies; D004938:Esophageal Neoplasms / Q000235:genetics*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D020641:Polymorphism, Single Nucleotide; D066247:Receptor, ErbB-4 / Q000235:genetics; D017411:Ribonucleoproteins, Small Nuclear / Q000235:genetics
chemical_list: C406815:GEMIN4 protein, human; C542542:MIRN146 microRNA, human; C542543:MIRN196 microRNA, human; D035683:MicroRNAs; D015778:Minor Histocompatibility Antigens; D017411:Ribonucleoproteins, Small Nuclear; C587689:ERBB4 protein, human; D066247:Receptor, ErbB-4