A Functional Variant rs2072915 is Associated with the Susceptibility and Mortality of Cervical Squamous Cell Carcinoma.

Abstract

PurposeGenetic variant has been demonstrated to be a risk factor for the occurrence and outcome of cervical squamous cell carcinoma (CSCC). From previous genome wide association studies, 6p21.32 has been identified as a susceptibility locus of CSCC. The purpose of this study was to investigate the association of a polymorphism rs2072915 located in 6p21.32 with the risk of CSCC and examine the potential mechanism of the rs2072915 in CSCC pathogenesis.Patients and MethodsThe rs2072915 was genotyped using polymerase chain reaction (PCR)-restriction fragment length polymorphism. miR-637 and RXRB mRNA expression levels in CSCC patients were examined using quantitative PCR. miR-637 target site was determined using the dual-luciferase reporter assay.ResultsThe rs2072915 was associated with a significantly increased risk (AA vs TT: adjusted OR = 2.48, 95% CI, 1.57–3.94, P < 0.001; AT/AA vs TT: adjusted OR = 1.38, 95% CI, 1.06–1.80, P = 0.018; A vs T: adjusted OR = 1.49, 95% CI, 1.21–1.84, P < 0.001, respectively) and shorter survival time of CSCC (P = 0.03). Patients with the rs2072915 AA genotype displayed lower levels of RXRB that is a target of miR-637.ConclusionThese findings suggest that the rs2072915 T > A change might augment the binding energy of miR-637 to RXRB, result in lower levels of RXRB, and thus contribute to the risk of CSCC.