Meta-analysis of the association between three microRNA polymorphisms and breast cancer susceptibility

Abstract

Single nucleotide polymorphisms (SNPs) in three microRNAs (miRNAs), rs2910164 in miR-146a, rs11614913 in miR-196a2, and rs3746444 in miR-499, have been associated with breast cancer (BC) susceptibility, but the evidence is conflicting. To obtain a more robust assessment of the association between these miRNA variants and BC risk, we carried out a meta-analysis through systematic literature retrieval from the PubMed and Embase databases. A total of 9 case-control studies on rs2910164, 12 on rs11614913, and 7 on rs3746444 were included. Pooled odds ratios and 95% confidence intervals were used to evaluate associations with BC risk. Overall analysis showed that rs2910164 was not associated with BC susceptibility in any genetic model, whereas rs11614913 was associated with a decreased risk in both the allelic contrast and recessive models, and rs3746444 imparted an increased risk in all genetic models. Stratified analyses showed that rs11614913 may decrease the risk of BC in the heterozygote model in Asians, and in all genetic models, except the heterozygote model, when the sample size is ≥ 500. Subgroup analysis indicated that rs3746444 was associated with increased risk of BC in Asians, but not Caucasians, at all sample sizes. This meta-analysis suggests that rs11614913 in miR-196a2 may decrease the risk of BC, while rs3746444 in miR-499 may increase it, especially in Asians when the sample size is large. We propose that rs11614913(C > T) and rs3746444 (A > G) may be useful biomarkers predictive of BC risk.

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

“…Therefore, the association of MIR499A rs3746444 polymorphism with breast cancer susceptibility among non-Asian populations remained unclear. Nevertheless, a major strength of the present work is that it included a larger number of studies and subjects compared to previous reports on this topic 45,46 . Thus, the present meta-analysis provided an updated and integrated estimate of the association between the polymorphism and breast cancer risk.…”

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

“…The human miR-146a gene at locus 5q34 has been linked with BRCA1/BRCA2 activity. The SNP rs2910164:G>C, located in the middle of the miRNA stem hairpin, leads to a change from a G:U pair to a C:U mismatch in the stem structure of the precursor molecule, altering the expression of mature miR-146a [ 44 ]. This SNP has been associated with the risk of various cancers [ 45 , 46 ], and with cancer-specific and ethnicity-dependent effects [ 23 , 37 ].…”

“…The variant rs3746444 in the mature miR-499-3p produces a change from an A:U pair to a G:U mismatch in the stem structure of the precursor molecule, leading to an altered processing and expression of the mature transcript [ 44 ], and potentially affecting the binding of the target mRNAs to the mature miRNA-3p [ 44 ]. miR-499 can target regulation of FOXO4 , PDCD4 , Sox6 , and Rod1 expression [ 47 , 48 , 49 ], all of which play important roles in the etiology of various cancers [ 48 ].…”

A genetic variant in microRNA-146a is associated with sporadic breast cancer in a Southern Brazilian Population

“…Also evidencing the differences of the effect of rs2910164 on the risk of BC in diverse populations, the allele rs2910164G was associated with increased risk of sporadic BC in Australians (OR =1.77, p < 10 -4 ; Uphadhyaya et al, 2015) and Iranians (OR = 1.91, p = 0.03; Barjui et al, 2017). Other studies, on the other hand, reported no association (Zhang et al, 2016;Mu et al, 2017).…”

“…The association of rs2910164 and BC was studied in several studies from different populations (Xu et al, 2013;Dai et al, 2015;Uphadhyaya et al, 2015;Barjui et al, 2017;Zhang et al, 2017). Dai et al (2015) showed that the effect of rs2910164 on BC susceptibility is different across populations.…”