Association between hsa-mir-146a genotype and tumor age-of-onset in BRCA1/BRCA2-negative familial breast and ovarian cancer patients.

ABSTRACT

An increasing body of evidence points to a possible role of microRNAs (miRNAs) in hereditary cancer syndromes. To evaluate the role of miRNA allelic variants in the susceptibility to familial breast and ovarian cancers in BRCA1/BRCA2-negative patients, we focused our attention on three miRNAs, miR-146a, miR-17 and miR-369, based on their affinity to either BRCA1 or BRCA2 messenger RNA and their localization on chromosome regions commonly deleted in those tumors. The analysis was performed on 101 Italian probands with ascertained familiarity for breast/ovarian cancer and tested negative for both BRCA1 and BRCA2 gene mutations. No allelic variant was detected for hsa-mir-17 and hsa-mir-369, and allelic and genotype frequencies for miR-146a rs2910164 single-nucleotide polymorphism (SNP) were comparable with that of 155 controls from the same population, ruling out a role for genetic variations in these three miRNAs as major determinants in cancer predisposition of BRCA1/BRCA2-negative patients. Instead, our study suggests that mir-146a rs2910164 SNP may impact on the age of cancer onset. In fact, subjects with mir-146a a GC or CC genotypes developed tumors at younger age compared with individuals with the GG genotype Thus, in contrast to a recent report, our data support the hypothesis by Shen and coworkers of an association between the C allele of hsa-mir-146a and early cancer onset and prompt further investigations on the relevance of this polymorphism in early familial breast/ovarian tumor development.