Lack of mutational events of RAS genes in sporadic thyroid cancer but high risk associated with HRAS T81C single nucleotide polymorphism (case–control study)

Abstract

High incidence of thyroid cancer worldwide indicates the importance of studying genetic alterations that lead to its carcinogenesis. Specific acquired RAS mutations have been found to predominate in different cancers, and HRAS T81C polymorphism has been determined to contribute the risk of various cancers, including thyroid cancer. We screened the exons 1 and 2 of RAS genes (HRAS, KRAS, and NRAS) in 60 consecutive thyroid tissue (tumor and adjacent normal) samples, and a case-control study was also conducted for HRAS T81C polymorphism in HRAS codon 27 using the polymerase chain reaction-restriction fragment length polymorphism to test the genotype distribution of 140 thyroid cancer patients in comparison with 170 cancer-free controls from a Kashmiri population. No mutation was found in any of the thyroid tumor tissue samples, but we frequently detected polymorphism at nucleotide 81 (T > C) in exon 1 of HRAS gene. In HRAS T81C SNP, frequencies of TT, TC, and CC genotypes among cases were 41.4, 38.6, and 20.0%, while in controls genotype frequencies were 84.1, 11.7, and 4.2%, respectively. A significant difference was observed in variant allele frequencies (TC + CC) between the cases and controls (58.6 vs. 16%) with odds ratio = 7.4; confidence interval (CI) = 4.3-12.7 (P < 0.05). Interestingly, combined TC and CC genotype abundantly presented in follicular thyroid tumor (P < 0.05). Moreover, a significant association of the variant allele (TC + CC) was found with nonsmokers (P < 0.05). This study shows that although thyroid cancer is highly prevalent in this region, the mutational events for RAS genes do not seem to be involved. Contrary to this HRAS T81C SNP of HRAS gene moderately increases thyroid cancer risk with rare allele as a predictive marker for follicular tumors.