Correlation between selected XRCC2, XRCC3 and RAD51 gene polymorphisms and primary breast cancer in women in Pakistan.

Z Qureshi,I Mahjabeen,R.M Baig,M.A Kayani

doi:10.7314/apjcp.2014.15.23.10225

Abstract

Genetic polymorphisms in homologous recombination repair genes cause an abnormal development of cancerous cells. In the present study we evaluated the possibility of breast cancer association with single nucleotide polymorphisms of RAD51, XRCC2 and XRCC3 genes. Polymorphisms selected in this study were RAD51 135G/C, XRCC2 Arg188His; and XRCC3 Thr241Met. Each polymorphism was genotyped using Polymerase chain reaction-restriction fragment length polymorphism in study cohort of 306 females (156 breast cancer patients and 150 controls). We observed that heterozygous variant genotype (GC) of RAD51 135 G/C polymorphism was associated with a significantly (OR=2.70; 95%CI (0.63-1.79); p<0.03) increased risk of breast cancer. In case of the XRCC3 gene we observed that frequency of heterozygous (OR=2.88; 95%CI (1.02-8.14); p<0.02) and homozygous (OR=1.46; 95%CI (0.89-2.40); p<0.04) genotype of Thr241Met polymorphism were significantly higher in breast cancer patients. For the Arg188His polymorphism of XRCC2, ~2fold increase in breast cancer risk (OR=1.6, 95%CI = 0.73-3.50) was associated with GA genotype with a p value for trend of 0.03. Our results suggest that the 135G/C polymorphism of the RAD51, Thr241Met polymorphism of XRCC3 and Arg188His polymorphism of XRCC2 can be independent markers of breast cancer risk in Pakistan.

Highlights

Genetic polymorphisms in homologous recombination repair (HRR) genes, which can lead to protein haploinsufficiency, have been associated with increased cancer risk (Areeshi, 2013)
In the present study we evaluated the possibility of breast cancer association with single nucleotide polymorphisms of RAD51, XRCC2 and XRCC3 genes
We observed that heterozygous variant genotype (GC) of RAD51 135 G/C polymorphism was associated with a significantly (OR=2.70; 95%confidence intervals (CI) (0.63-1.79); p

Summary

Introduction

Genetic polymorphisms in homologous recombination repair (HRR) genes, which can lead to protein haploinsufficiency, have been associated with increased cancer risk (Areeshi, 2013). XRCC2 is second important protein of HRR pathway and has been shown to interact with RAD51 and RAD51 like proteins (Andreassi et al, 2009; Tambini et al, 2010) Insufficiency of this protein cause increased errors in chromosome segregation and other chromosomal aberrations (Shin et al, 2008). The most common XRCC2 Arg188His G>A (R188H, rs3218536) polymorphism has been widely studied in association with breast cancer susceptibility and other cancers (RomanowiczMakowska et al, 2012; Fayaz et al, 2013; He et al, 2014). To identify the association of RAD 51 (5’untranslated region 135 G>C), XRCC2 (Arg188His), and XRCC3 (Thr241Met) polymorphisms with the risk of breast cancer, we conducted a population-based nested casecontrol study including 156 cases and 150 cancer-free controls in a Pakistani population and it is postulated that these SNPs can possibly be used as predictive factors for breast cancer prognosis

Materials and Methods

Results

Discussion