Genetic Variants in pre-miR-146a, pre-miR-499, pre-miR-125a, pre-miR-605, and pri-miR-182 Are Associated with Breast Cancer Susceptibility in a South American Population

• Published in: Genes 2018-08, Vol.9 (9), p.427
• Main Authors: Morales, Sebastián, De Mayo, Tomas, Gulppi, Felipe Andrés, Gonzalez-Hormazabal, Patricio, Carrasco, Valentina, Reyes, José Miguel, Gómez, Fernando, Waugh, Enrique, Jara, Lilian
• Format: Article
• Language: English
• ISSN: 2073-4425; 2073-4425
• DOI: 10.3390/genes9090427

Breast cancer (BC) is one of the most frequent tumors affecting women worldwide. microRNAs (miRNAs) single-nucleotide polymorphisms (SNPs) likely contribute to BC susceptibility. We evaluated the association of five SNPs with BC risk in non-carriers of the -mutation from a South American population. The SNPs were genotyped in 440 Chilean -negative BC cases and 1048 controls. Our data do not support an association between rs2910164:G>C or rs3746444:A>G and BC risk. The rs12975333:G>T is monomorphic in the Chilean population. The pre-miR-605 rs2043556-C allele was associated with a decreased risk of BC, both in patients with a strong family history of BC and in early-onset non-familial BC (Odds ratio (OR) = 0.5 [95% confidence interval (CI) 0.4⁻0.9] = 0.006 and OR = 0.6 [95% CI 0.5⁻0.9] = 0.02, respectively). The rs4541843-T allele is associated with increased risk of familial BC. This is the first association study on rs4541843 and BC risk. Previously, we showed that the -rs3803662:C>T was significantly associated with increased risk of familial BC. Given that mRNA is a target of miR-182, and that both the rs3803662-T and pri-miR-182 rs4541843-T alleles are associated with increased BC risk, we evaluated their combined effect. Risk of familial BC increased in a dose-dependent manner with the number of risk alleles ( -trend = 0.0005), indicating an additive effect.