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

Investigating the association of rs2910164 with cancer predisposition in an Irish cohort.
Author Information (click to view)

McVeigh TP, Mulligan RJ, McVeigh UM, Owens PW, Miller N, Bell M, Sebag F, Guerin C, Quill DS, Weidhaas JB, Kerin MJ, Lowery AJ,


McVeigh TP, Mulligan RJ, McVeigh UM, Owens PW, Miller N, Bell M, Sebag F, Guerin C, Quill DS, Weidhaas JB, Kerin MJ, Lowery AJ, (click to view)

McVeigh TP, Mulligan RJ, McVeigh UM, Owens PW, Miller N, Bell M, Sebag F, Guerin C, Quill DS, Weidhaas JB, Kerin MJ, Lowery AJ,

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Endocrine connections 2017 09 126(8) 614-624 doi 10.1530/EC-17-0196

Abstract
INTRODUCTION
MicroRNAs (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.

METHODS
The 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.

RESULTS
The 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).

CONCLUSION
The rs2910164 variant in MIR146A is significantly associated with DTC, but is not significantly associated with BC in this cohort.

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