Purpose: Genetic 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 methods: The 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.
Results: The 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.
Conclusion: These 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.
Keywords: cervical squamous cell carcinoma; miR-637; polymorphism; survival.
© 2021 Li et al.