DNA Repair Mechanism Gene, XRCC1A (Arg194Trp) but not XRCC3 (Thr241Met) Polymorphism Increased the Risk of Breast Cancer in Premenopausal Females: A Case–Control Study in Northeastern Region of India

Abstract

X-ray repair cross complementary group gene is one of the most studied candidate gene involved in different types of cancers. Studies have shown that X-ray repair cross complementary genes are significantly associated with increased risk of breast cancer in females. Moreover, studies have revealed that X-ray repair cross complementary gene polymorphism significantly varies between and within different ethnic groups globally. The present case–control study was aimed to investigate the association of X-ray repair cross complementary 1A (Arg194Trp) and X-ray repair cross complementary 3 (Thr241Met) polymorphism with the risk of breast cancer in females from northeastern region of India. The present case–control study includes histopathologically confirmed and newly diagnosed 464 cases with breast cancer and 534 apparently healthy neighborhood community controls. Information on sociodemographic factors and putative risk factors were collected from each study participant by conducting face-to-face interviews. Genotyping of X-ray repair cross complementary 1A (Arg194Trp) and X-ray repair cross complementary 3 (Thr241Met) was carried out by polymerase chain reaction-restriction fragment length polymorphism. For statistical analysis, both univariate and multivariate logistic regression analyses were performed. We also performed stratified analysis to find out the association of X-ray repair cross complementary genes with the risk of breast cancer stratified based on menstrual status. This study revealed that tryptophan allele (R/W-W/W genotype) in X-ray repair cross complementary 1A (Arg194Trp) gene significantly increased the risk of breast cancer (adjusted odds ratio = 1.44, 95% confidence interval = 1.06-1.97, P < .05 for R/W-W/W genotype). Moreover, it was found that tryptophan allele (W/W genotype) at codon 194 of X-ray repair cross complementary 1A (Arg194Trp) gene significantly increased the risk of breast cancer in premenopausal females (crude odds ratio = 1.66, 95% confidence interval = 1.11-2.46, P < .05 for R/W-W/W genotype). The present study did not reveal any significant association of X-ray repair cross complementary 3 (Thr241Met) polymorphism with the risk of breast cancer. The present study has explored that X-ray repair cross complementary 1A (Arg194Trp) gene polymorphism is significantly associated with the increased risk of breast cancer in premenopausal females from northeastern region of India which may be beneficial for prognostic purposes.

<p>Association of <em>XRCC1</em>, <em>XRCC2</em> and <em>XRCC3</em> Gene Polymorphism with Esophageal Cancer Risk</p>

“…A previous study from the north-eastern region of India has reported no association of this polymorphism with breast cancer. 90 From Indian subcontinent, two populations practicing consanguineous marriages reported an association with increased risk, for colorectal cancer in Kashmiri population 50 and breast cancer in Pakistani population. 91 For XRCC3 p.Thr241Met polymorphism, no association was reported with gastric cancer in Italian population 92 and with colorectal cancer in the West Algerian population 93 but an association with an increased risk was reported for lung cancer in an Italian population, 23 oral SCC in Thai population, 94 and gastric cancer in the Chinese population.…”

Homologous recombination DNA repair gene RAD51, XRCC2 & XRCC3 polymorphisms and breast cancer risk in South Indian women

“…Furthermore, a study by Santos et al [39] additionally observed that the XRCC3 Thr241Met variant was slightly associated with an increased risk of BC in individuals with elevated chromosomal damage. However, reports from certain ethnicities have observed a lack of association between XRCC3 Thr241Met variant and BC risk [25,26,[40][41][42][43].…”

Polymorphism in XRCC1, XRCC2, XRCC3 Genes and Risk of Gastrointestinal Cancer: A Case-Control Study from South-Western Maharashtra

“…Similarly, association of XRCC2 and XRCC3 polymorphism with lung (12) and breast cancer (13) have been studied. However, findings from earlier studies continued with contradiction which failed to prove the association of SNPs in XRCC genes with risk of multiple cancers (14,15) . Number of studies demonstrated the pronounced susceptibility of gastric cancer in association with SNPs of XRCC genes (16,17) .…”