Genetic polymorphisms in miRNAs targeting the estrogen receptor and their effect on breast cancer risk

Abstract

Breast cancer is the cancer that most commonly affects women worldwide. This type of cancer is genetically complex, but is strongly linked to steroid hormone signaling systems. Because microRNAs act as translational regulators of multiple genes, including the steroid nuclear receptors, single nucleotide polymorphisms (SNPs) in microRNA genes can have potentially wide-ranging influences on breast cancer development. Thus, this study was conducted to investigate the relationships between six SNPs (rs6977848, rs199981120, rs185641358, rs113054794, rs66461782, and rs12940701) located in four miRNA genes predicted to target the estrogen receptor (miR-148a, miR-221, miR-186, and miR-152) and breast cancer risk in Caucasian Australian women. By using high resolution melt analysis (HRM) and polymerase chain reaction- restriction fragment length polymorphism (PCR–RFLP), 487 samples including 225 controls and 262 cases were genotyped. Analysis of their genotype and allele frequencies indicated that the differences between case and control populations were not significant for rs6977848, rs66461782, and rs12940701 because their p-values are 0.81, 0.93, and 0.1, respectively, which are all above the threshold value (p = 0.05). Our data thus suggests that these SNPs do not affect breast cancer risk in the tested population. In addition, rs199981120, rs185641358, and rs113054794 could not be found in this population, suggesting that these SNPs do not occur in Caucasian Australians.

MicroRNA-196a2 Biomarker and Targetome Network Analysis in Solid Tumors

“…This could in part explain the cancer risk this SNP implies in some types of cancers in our study and the absence of this risk in other types although showing high level of its expression. The tested SNP could affect the behavior of miRNA-196a2 in some way significant to the progression of some types of cancer, but that it did not affect risk of developing the disease [78]. In the current study, T allele was associated with risk of specific types of cancer, although the C allele was associated with higher expression levels; a finding that seems to be contradictory at the first time.…”

“…This finding, in addition, might emphasize the differences in cell origin between the tumor types and subsequently the differential expression of mir196a2 in these types of cancer [76] or could reflect the possibility that mir-196a2 can act as either oncomir in some types of cancer or tumor suppressor miR in others [77]. In addition, this aberrant expression may be owing to the effect of other SNPs at different loci or be caused by other effects, such as changes in DNA copy number in cancer cells or DNA methylation [78], the role of RNAbinding proteins that can either induce or suppress the expression of miRNAs and control their binding to their targets [79], or the involvement of other non-coding RNAs such as long non-coding RNAs, small interfering RNAs, small nucleolar RNAs, small nuclear RNAs, Piwi-interacting RNAs, and circular RNAs [80], which could also contribute to the differential expression of this miRNA observed in the different cancer types in the current study or between our cases and previous research.…”

Association of miR-146 rs2910164, miR-196a rs11614913, miR-221 rs113054794 and miR-224 rs188519172 polymorphisms with anti-TNF treatment response in a Greek population with Crohn’s disease

“…Moreover, rs113054794 SNP of miR-221 was not detected in our population, indicating that this polymorphism is probably highly rare in Caucasian populations. In accordance to our results, Nguyen-Dien et al[ 40 ] have also demonstrated this SNP’s absence in a Caucasian population studied for correlation of miRNA variants and risk of breast cancer.…”

ESR1 mutations affect anti-proliferative responses to tamoxifen through enhanced cross-talk with IGF signaling

“…Using sensitive ddPCR assays, Takeshita et al reported that 2.5% of primary breast cancer specimens contained ESR1 mutations, with the Y537S mutation being the most frequent 25 . To address whether ESR1 mutations might predict response to Tam in primary breast cancers, we used ddPCR sequencing of archived DNAs from 203 primary tumors treated with Tam monotherapy 11 .…”