HRAS T81C polymorphism modulates risk of urinary bladder cancer and predicts advanced tumors in ethnic Kashmiri population

Abstract

ObjectiveSpecific acquired HRAS mutations have been found to predominate in bladder cancer, and HRAS T81C polymorphism has been determined to contribute the risk of various cancers, including bladder cancer. Materials and methodsWe screened the exon 1and 2 of HRAS and frequently detected polymorphism at nucleotide 81T to C (exon 1). A case-control study was conducted using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to test the genotype distribution of 140 bladder cancer patients in comparison with 160 cancer-free controls from a Kashmiri population. ResultsIn HRAS T81C SNP, frequencies of TT, TC, and CC genotypes among controls were 84.4%, 15.6%, and 0.0%, while in cases allele frequencies were 64.3%, 30%, and 5.7%, respectively. A significant differences was observed between the control and cases with odds ratio (OR) = 3.0 and 95% confidence interval (CI) = 1.74–5.20 (P = 0.000). Interestingly, combined TC and CC genotype abundantly presented in high grade (OR = 5.4 and 95% CI = 2.8–10.2; P < 0.00) and in advanced tumors (OR = 3.3, 95% CI = 1.71–6.30; P < 0.05). A significant association of the variant allele (TC+CC) was found with male subjects (≥50) and ever smokers (P = 0.001). ConclusionIt is evident from our study that HRAS T81C SNP moderately increases bladder cancer risk, and rare allele is a predictive marker of advanced bladder tumors.