Association Between Genetic Polymorphisms in the Promoters of Let-7 and Risk of Cervical Squamous Cell Carcinoma

Numerous reports showed low levels of let-7 family in cervical cancer, acting as tumor suppressors by regulating multiple target genes. Genetic variants in the promoter of miRNA have been reported to influence individuals' susceptibility to human diseases. We aimed to investigate the association of rs10877887 and rs13293512 polymorphisms in the promoters of let-7 with risk of cervical squamous cell carcinoma (CSCC). A total of 331 patients with CSCC and 358 controls were included. Genotyping of rs10877887 was done using polymerase chain reaction-restriction fragment length polymorphism analysis. Genotyping of rs13293512 was performed using Taqman allelic discrimination. Relative expression of let-7 family was determined using quantitative real-time polymerase chain reaction. The rs10877887CC genotype was significantly associated with an increased risk of CSCC compared with the rs10877887TT (adjusted OR=2.11, 95% CI, 1.31-3.40, p-value=0.002) or rs10877887 TT/CT genotypes (adjusted OR=2.11, 95% CI, 1.34-3.31, p-value<0.001). Similarly increased risk of CSCC was observed when compared rs10877887T with rs10877887C allele (adjusted OR=1.35, 95% CI, 1.08-1.69, p-value=0.008). Combined analysis showed that individuals carrying the genotypes of rs10877887CC+rs13293512CC had a 4.78-fold higher risk to develop CSCC compared with those carrying the genotypes of rs10877887CT/TT+rs13293512CT/TT (OR=4.78, 95% CI, 1.78-12.84, p-value=0.001). Additionally, patients harboring rs10877887CC genotype had a lower level of let-7i in CSCC tissues (p-value=0.02). This observation indicates that rs10877887 may be a useful biomarker for the etiology of CSCC.