Background and aim: Exonuclease 1 (EXO1) is an essential member of the RAD2 nuclease family which is involved in mismatch repair system and contributes to the maintenance of genomic stability, modulation of DNA recombination and cell cycle arrest mediation. Potential polymorphism in EXO1 may have the ability to control cancer risks by influencing the repair activity. K589E (rs1047840) is a potentially functional polymorphism in EXO1 gene and we hypothesized that it might be associated with risk of breast cancer in Bangladesh.

Method: We designed a case-control study consisting of 184 subjects with breast cancer and 200 healthy controls to identify the effect of K589E polymorphism on breast cancer susceptibility and clinicopathological features in Bangladeshi women. Genotype determination was performed by PCR-RFLP method.

Results: After the adjustment of age and weight, a significant association was found between EXO1 K589E alleles and genotypes and risk of breast cancer. The frequencies of the three genotypes G/G, G/A, and A/A were 49, 42, and 9% in cases whereas 69, 27.5, and 3.5% in controls, respectively. The heterozygote G/A genotype and combined G/A+A/A genotypes showed 2.12-fold (OR=2.12, 95% CI=1.3733 - 3.2822 p=0.0007) and 2.27-fold (OR=2.27, 95% CI=1.5001 - 3.4493, p=0.0001) increased risk of breast cancer, respectively when compared with homozygous G/G genotypes. The variant A allele also was associated with increased risk of breast cancer (OR= 3.46, 95% CI=1.3720 - 8.7571, p=0.0086). Analysis of clinicopathological characteristics and genotype distribution also showed a significant correlation.

Conclusion: Our results revealed that EXO1 K589E polymorphism could be a potential predisposing risk factor in genetic susceptibility to breast cancer in Bangladesh.

Citation Format: Md. Mustafizur Rahman, Md. Mahmudul Kabir, Md. Abdur Rahman, Amir Hossain, Md. Golam Hossain. Impact of EXO1 (K589E) single nucleotide polymorphism on breast cancer risk in Bangladeshi women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2216.