Abstract 1617: Genetic polymorphisms in DNA repair genes XRCC1 and 3 are associated with increased risk of breast cancer in Bangladeshi population

Abstract

Abstract Background: Breast cancer is the most commonly occurring cancer in women worldwide and its prevalence vary among different ethnic groups. Genetic polymorphisms in DNA repair genes may affect individual variation in DNA repair capacity which may contribute to individual susceptibility for developing various cancers. This study aimed to investigate the contribution of polymorphisms in two DNA repair genes, namely XRCC1 (Arg399Gln, rs25487) and XRCC3 (Thr241Met, rs861539) to breast cancer risk in Bangladeshi females and their role as susceptibility markers. Methods: A case-control study comprising 121 breast cancer patients and 133 healthy volunteers was conducted taking the age, breast feeding status, menopausal status, education etc into account. Genomic DNA isolated from peripheral blood was used to genotype the target polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Risk-stratified subgroup analyses were conducted to find out the association between the genotypes and age-, menopause-, lactating status-related characteristics of breast cancer patients. Results: A significant positive association was found between XRCC1 (Arg399Gln,) and XRCC3 (Thr241Met) polymorphisms and breast cancer risk in the studied population. In case of XRCC1 Arg399Gln polymorphism, the heterozygous Arg/Gln (G/A) and homozygous Gln/Gln (A/A) genotypes showed 1.78-fold (OR=1.78, 1.0084 to 3.1442, p=0.0467) and 2.41-fold (OR=2.41, 95% CI= 1.0354 to 5.5914, p=0.0413) increased risk of breast cancer, respectively when compared with homozygous Arg/Arg genotype. The presence of any XRCC1 Gln (Arg/Gln or Gln/Gln) was associated with 1.93-fold increased risk (OR=1.93, 95% CI= 1.1574 to 3.2290, p=0.0118). The variant Gln (A) allele also was associated with increased risk of breast cancer (OR=1.78, 95% CI= 1.1885 to 2.6805, p=0.0052). The Gln/Gln genotype was more prevalent in breast cancer cases at ages 55 or above and in menopausal state. In case of XRCC3 (Thr241Met) polymorphism, Thr/Met (C/T) heterozygote, and combined Thr/Met+Met /Met (C/T+T/T) genotypes were significantly associated with 1.85- and 1.89- fold higher risk of breast cancer, respectively (OR=1.85, 95% CI=1.0815 to3.1834, p=0.0248; OR=1.89, 95% CI=1.1199 to 3.1908, p=0.0171, respectively). The variant Met (T) allele showed significant association with increased susceptibility (1.70-fold) to breast cancer (OR=1.70, 95% CI=1.0849 to 2.6172, p= 0.0206). Among breast cancer cases significant differences in genotype frequency were evident in patients with age 55 years or above and with menopause. Conclusion: Our results suggest that XRCC1 (Arg399Gln) and XRCC3 (Thr241Met) polymorphisms are associated with increased risk of breast cancer in Bangladeshi females. In addition, this association was significantly related to age and lactating status. Citation Format: Md. Mustafizur Rahman, Nupur Rani Hawlader, Md. Mostafizur Rahman, Md. Amir Hossain. Genetic polymorphisms in DNA repair genes XRCC1 and 3 are associated with increased risk of breast cancer in Bangladeshi population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1617.