Genetic Variants in miRNAs Associated with Renal Cell Carcinoma (RCC) Risk: A Pilot Study in North Indian Population (original) (raw)

2014, Indian Journal of Clinical Biochemistry

Renal cell carcinoma (RCC) is a leading cause of cancer mortality. Characterizing miRNA expression in RCC by targeting pathways involved in the action of miRNAs, may lead to discovery of some novel prognostic as well as diagnostic biomarkers. In the present study, we aimed at finding the association of various aberrations in miRNAs to be associated with risk of RCC. In this study we selected 100 histologically confirmed RCC patients and 225 healthy unrelated controls with frequency matched age and sex. Genotyping was done by PCR-RFLP for hsa-mir-146aG/C, hsa-mir-27aA/G, hsa-mir-196a2C/T, hsa-mir-499A/G. However, hsa-mir-125aG/T was genotyped by allelic discrimination Taqman Ò assay. Statistical logistic regression and genetic model was used to find out the genetic effects on the risk of RCC and interactions between polymorphism of all four miRNAs and risk factors. The SNP hsa-mir-196aC/T demonstrated significant high risk for heterozygous genotype (CT; p \ 0.001, OR = 3.206, 95 % CI 1.882-5.462) and variant genotype (TT; p = 0.021, OR = 3.57, 95 % CI 1.209-10.54). Similar pattern was seen in the dominant model (CT?TT; p \ 0.001, OR = 2.992, 95 % CI 1.798-4.978) with similar effects at allelic level, T allele (p \ 0.001, OR = 1.902, 95 % CI 1.335-2.709) also for hsa-mir-196aC/T. In case of hsa-mir499T/C SNP, when the three genotypes were compared, the heterozygous genotype (TC) was found to be associated (p = 0.026, OR = 1.61, 95 % CI 1.05-2.45) with RCC risk. Whereas, hsa-mir27aA/G and hsa-mir146aC/G revealed reduced risk to RCC. Our results suggested that the hsa-mir196a2C/T and hsa-mir499T/C perhaps could be used as a predictive marker for RCC in North Indian population if further validated functionally with varied ethnicities.