Abstract 4400: The let-7 microRNA binding site variant in the KRAS 3′-UTR is not associated with the risk of head and neck cancer

Abstract

Abstract The KRAS gene is activated by somatic mutations in many cancer types. However, KRAS mutations are relatively rare in squamous cell carcinomas. In squamous cell cancers of the head and neck (HNSCC) amplification of the KRAS gene has been shown to promote tumor growth. miRNAs are short non-coding RNAs which play an important role as regulators of gene expression. They bind to the 3′-untranslated regions (UTRs) of the mRNAs and prevent translation of their target genes. SNPs in the miRNA binding sites are associated with disease risk and prognosis. The let-7 family of miRNAs regulate multiple oncogenes including the KRAS gene and have been shown to play a critical role in different cancer types. A functional polymorphism in the KRAS gene, not included in the GWAS platforms has been identified by candidate gene approach and was found to be a genetic marker of cancer risk and increased susceptibility to the carcinogenic effects of tobacco smoke. The polymorphism is referred to as the LCS6 (let-7 complementary site 6) variant and disrupts the let-7 binding site leading to higher KRAS expression. Such an increase in KRAS expression associated with the variant allele may represent an alternative form of KRAS activation in HNSCC and could lead to impairment of the EGFR signaling. In this study we evaluated the frequency of the KRAS variant in 216 patients with head and neck cancer and 85 healthy individuals. DNA was extracted from whole blood prior to chemotherapy or radiotherapy. The variant allele was analyzed by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis. Genotype and allele frequencies were evaluated using the De-Finetti case control program. 13 % of the patients were heterozygous and 3 patients (1.5 %) were homozygous for the variant allele. The polymorphism was present in heterozygous form in 12 % of the controls. No homozygous individual was detected in the control group. The frequencies of the variant allele were 92 % and 94 % in the patients and controls, respectively. Our data indicate that the KRAS let-7 LCS6 variant allele is not associated with an increased risk of HNSCC. Citation Format: Nejat Dalay, Semra Demokan, Yusufhan Suoglu, Rasim Yilmazer, Murat Ulusan. The let-7 microRNA binding site variant in the KRAS 3′-UTR is not associated with the risk of head and neck cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4400. doi:10.1158/1538-7445.AM2014-4400