Association of single nucleotide polymorphisms in Pre-miR-27a, Pre-miR-196a2, Pre-miR-423, miR-608 and Pre-miR-618 with breast cancer susceptibility in a South American population.

Sebastián Morales,Patricio Gonzalez-Hormazabal,Fernando Gomez,Ricardo Fernandez-Ramires,José Miguel Reyes,Teresa Bravo,Enrique Waugh,Lilian Jara,Felipe Gulppi

doi:10.1186/s12863-016-0415-0

Abstract

BackgroundMicroRNAs (miRNAs) are a novel class of endogenous, non-coding, single-stranded RNAs capable of regulating gene expression by suppressing translation or degrading mRNAs. Single nucleotide polymorphisms (SNP) can alter miRNA expression, resulting in diverse functional consequences. Previous studies have examined the association of miRNA SNPs with breast cancer (BC) susceptibility. The contribution of miRNA gene variants to BC susceptibility in South American women had been unexplored. Our study evaluated the association of the SNPs rs895819 in pre-miR27a, rs11614913 in pre-miR-196a2, rs6505162 in pre-miR-423, rs4919510 in miR-608, and rs2682818 in pre-mir-618 with familial BC and early-onset non-familial BC in non-carriers of BRCA1/2 mutations from a South American population.ResultsWe evaluated the association of five SNPs with BC risk in 440 cases and 807 controls. Our data do not support an association of rs11614913:C > T and rs4919510:C > G with BC risk. The rs6505162:C > A was significantly associated with increased risk of familial BC in persons with a strong family history of BC (OR = 1.7 [95 % CI 1.0–2.0] p = 0.05). The rs2682818:C > A genotype C/A is associated with an increased BC risk in non-familial early-onset BC. For the rs895819:A > G polymorphism, the genotype G/G is significantly associated with reduced BC risk in families with a moderate history of BC (OR = 0.3 [95 % CI 0.1–0.8] p = 0.01).ConclusionsThe contribution of variant miRNA genes to BC in South American women had been unexplored. Our findings support the following conclusions: a) rs6505162:C > A in pre-miR-423 increases risk of familial BC in families with a strong history of BC; b) the C/A genotype at rs2682818:C > A (pre-miR-618) increases BC risk in non-familial early-onset BC; and c) the G/G genotype at rs895819:A > G (miR-27a) reduces BC risk in families with a moderate history of BC.

Highlights

MicroRNAs are a novel class of endogenous, non-coding, single-stranded RNAs capable of regulating gene expression by suppressing translation or degrading mRNAs
Considering the proceeding information, in this study we evaluated the association of rs895819 in pre-miR27a, rs11614913 in pre-miR-196a2, rs6505162 in pre-miR-423, rs4919510 in miR-608, and rs2682818 in pre-mir-618 with familial breast cancer (BC) and early-onset non-familial BC in non-carriers of BRCA1/2 mutations from a South American population
The observed genotype frequencies for four of the five polymorphisms were in Hardy-Weinberg equilibrium in controls (p = 0.12 for rs11614913:C > T, p = 0.7 for rs6505162:C > A, p = 0.3 for rs4919510:C > G, and p = 0.8 for rs2682818:C > A, respectively), while for rs895819:A > G the p-value was 0.02

Summary

Introduction

MicroRNAs (miRNAs) are a novel class of endogenous, non-coding, single-stranded RNAs capable of regulating gene expression by suppressing translation or degrading mRNAs. Our study evaluated the association of the SNPs rs895819 in pre-miR27a, rs11614913 in pre-miR-196a2, rs6505162 in pre-miR-423, rs4919510 in miR-608, and rs2682818 in pre-mir-618 with familial BC and early-onset non-familial BC in non-carriers of BRCA1/2 mutations from a South American population. With the exception of one study in a Brazilian population [33], the contribution of variant miRNA genes to BC in South American women had been unexplored. The variant rs11614913, located in the mature miR-196a-3p sequence, could lead to less efficient processing of the miRNA precursor to its mature form and diminish its capacity to regulate target genes such as HOXB2, HOXB3, HOXC3, HOXB5, GADD45G, INHBB, and TP63 [39]. Zhao et al [43], demonstrated that the SNP rs6505162 in pre-miR423 affects mature miR expression, and miR-423 plays a potentially oncogenic role in breast tumorigenesis. Considering the proceeding information, in this study we evaluated the association of rs895819 in pre-miR27a, rs11614913 in pre-miR-196a2, rs6505162 in pre-miR-423, rs4919510 in miR-608, and rs2682818 in pre-mir-618 with familial BC and early-onset non-familial BC in non-carriers of BRCA1/2 mutations from a South American population

Methods

Results

Discussion

Conclusion