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

Abstract

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 BRCA1/2-mutation from a South American population. The SNPs were genotyped in 440 Chilean BRCA1/2-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] p = 0.006 and OR = 0.6 [95% CI 0.5–0.9] p = 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 TOX3-rs3803662:C>T was significantly associated with increased risk of familial BC. Given that TOX3 mRNA is a target of miR-182, and that both the TOX3 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 (p-trend = 0.0005), indicating an additive effect.

Genetic Variants in miRNAs Are Associated With Risk of Non-syndromic Tooth Agenesis

“…Rs2043556 was located in pre-miR-605 and our study showed that this SNP was associated with differential expression of mature miR-605 (including miR-605-3p and miR-605-5p), consistent with the study by Zhou et al (2017) Pre-miR-605 had previously been linked to a number of malignancies, such as prostate cancer, breast cancer (Morales et al, 2018), non-small-cell lung cancer (Zhou and Li, 2019), and oral squamous cell carcinoma (Miao et al, 2016), suggesting its potential as a biomarker for cancer. Interestingly, tooth agenesis and cancer development share common molecular pathways and previous study found that almost all types of tumors were more common in families with tooth agenesis (Kuchler et al, 2013).…”

Association between MIR499A rs3746444 polymorphism and breast cancer susceptibility: a meta-analysis

“…The reference list of these records were also hand-searched to identify additional studies. Ultimately, 12 records (which comprised 13 studies) were included in the meta-analysis 15,16,[24][25][26][27][28][29][30][31][32][33] . We also included preliminary data from our laboratory in the meta-analysis, making the total number of included studies 14.…”

“…A number of studies have examined the association of the polymorphism with breast cancer susceptibility, but the results obtained have been inconsistent. For instance, while He et al 15 demonstrated that the variant allele of MIR499A rs3746444 polymorphism was significantly associated with an increased susceptibility to breast cancer, Morales et al 16 did not find any significant association. One of the major reasons for the inconsistency of study results in genetic association studies is the limited sample size and thus, low statistical power of the individual studies 17,18 .…”

Associations of Single Nucleotide Polymorphism in miR-146a Gene with Susceptibility to Breast Cancer in the Iranian Female

“…By way of illustration, the mutations in the BRCA1/2 genes are responsible for an average risk of 16-20% for hereditary breast cancer. Recent research, however, has produced evidences to support the role microRNAs (miRNAs) play in development and progression of breast cancer (Morales et al, 2018). The human genome encodes more than 1,000 miRNAs (Wang et al, 2013).…”