Investigating the association of rs2910164 with cancer predisposition in an Irish cohort

Abstract

IntroductionMicroRNAs (miRNAs) are small noncoding RNA molecules that exert post-transcriptional effects on gene expression by binding with cis-regulatory regions in target messenger RNA (mRNA). Polymorphisms in genes encoding miRNAs or in miRNA–mRNA binding sites confer deleterious epigenetic effects on cancer risk. miR-146a has a role in inflammation and may have a role as a tumour suppressor. The polymorphism rs2910164 in the MIR146A gene encoding pre-miR-146a has been implicated in several inflammatory pathologies, including cancers of the breast and thyroid, although evidence for the associations has been conflicting in different populations. We aimed to further investigate the association of this variant with these two cancers in an Irish cohort.MethodsThe study group comprised patients with breast cancer (BC), patients with differentiated thyroid cancer (DTC) and unaffected controls. Germline DNA was extracted from blood or from saliva collected using the DNA Genotek Oragene 575 collection kit, using crystallisation precipitation, and genotyped using TaqMan-based PCR. Data were analysed using SPSS, v22.ResultsThe total study group included 1516 participants. This comprised 1386 Irish participants; 724 unaffected individuals (controls), 523 patients with breast cancer (BC), 136 patients with differentiated thyroid cancer (DTC) and three patients with dual primary breast and thyroid cancer. An additional cohort of 130 patients with DTC from the South of France was also genotyped for the variant. The variant was detected with a minor allele frequency (MAF) of 0.19 in controls, 0.22 in BC and 0.27 and 0.26 in DTC cases from Ireland and France, respectively. The variant was not significantly associated with BC (per allele odds ratio = 1.20 (0.98–1.46), P = 0.07), but was associated with DTC in Irish patients (per allele OR = 1.59 (1.18–2.14), P = 0.002).ConclusionThe rs2910164 variant in MIR146A is significantly associated with DTC, but is not significantly associated with BC in this cohort.

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

“…We also did not find any association between genotypes of rs2910164 and regional lymph node invasion, immunohistochemical subgroups or tumour grade, which suggests a lack of association of rs2910164 with tumour progression. This result is similar to studies in the Irish population (McVeigh et al, 2017) and the Chinese (Qi et al, 2015).…”

“…Studying sporadic BC cases, we did not find any association of rs2910164 with the age of diagnosis. These findings were similar to those observed in other studies with sporadic BC, and this possible difference in the association between sporadic and hereditary BC with rs2910164 is still not understood (Cardeñosa et al, 2012;Qi et al, 2015;Barjui et al, 2017;Mcveigh et al, 2017).…”

“…There are few case-controls studies focusing the polymorphism rs2910164 in association with BC. Five studies were described in the European population (Catucci et al, 2010;Pastrello et al, 2010;Garcia et al, 2011;Cardeñosa et al, 2012;McVeigh et al, 2017) and one in an Australian Caucasian population (Uphadhyaya et al, 2015). The majority of these studies have focused on familial BC (Catucci et al, 2010;Pastrello et al, 2010;Garcia et al, 2011;Cardeñosa et al, 2012).…”

Evidences from a Systematic Review and Meta-Analysis Unveil the Role of MiRNA Polymorphisms in the Predisposition to Female Neoplasms

“…The full texts of the remaining 79 records were evaluated and 10 articles were excluded for the following reasons: insufficient reported data ( n : 4) [16,17,18,19], studying other genes or polymorphisms ( n : 3) [20,21,22], not a case-control design ( n : 2) [23,24], and a duplicate study ( n : 1) [25]. Finally, a total of 69 articles remained [26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85<...>…”

“…Twenty-eight association studies with a total of 11,071 cases and 12,312 controls were included in the meta-analysis of miR-146a rs2910164 and the risk of female neoplasms (Table 1 and Figure 2) [26,28,32,33,34,35,36,38,42,46,47,50,52,55,60,63,67,68,69,70,73,74,77,78,80,81,83,92]. Among these, there were studies that were carried out among Asians ( n : 20), Caucasians ( n : 5), Africans ( n : 1), or South Americans ( n : 1).…”