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

Abstract

Background

Genetic polymorphisms in DNA repair genes, XRCC1 (Arg399Gln) and XRCC3 (Thr241Met), may affect their DNA repair capacity leading to individual variation in breast cancer susceptibility among Bangladeshi females.

Methods

The case–control study comprised 121 breast cancer patients and 133 healthy controls. Genomic DNA isolated from peripheral blood was genotyped for target SNPs using PCR-RFLP method.

Results

For XRCC1, heterozygous Arg/Gln and homozygous Gln/Gln genotypes showed 1.78-fold (95% CI 1.0084 to 3.1442, p = 0.0467) and 2.41-fold (95% CI 1.0354 to 5.5914, p = 0.0413) increased risk of breast cancer, respectively, when compared with Arg/Arg genotype. The presence of any XRCC1 Gln showed association with 1.93-fold increased risk. The variant Gln allele was associated with increased risk of breast cancer (95% CI 1.1885 to 2.6805, p = 0.0052). For XRCC3, Thr/Met heterozygous and combined Thr/Met + Met/Met genotypes were associated with 1.85-fold (95% CI 1.0815 to 3.1834, p = 0.0248) and 1.89-fold (95% CI 1.1199 to 3.1908, p = 0.0171) higher risk, respectively, compared to Thr/Thr genotypes. The variant Met allele showed significant association with increased breast cancer susceptibility. Among cases genotype frequencies were significantly different in patients with age 55 or above, and with menopause and diabetes.

Conclusion

XRCC1 (Arg399Gln) and XRCC3 (Thr241Met) polymorphisms may be associated with increased breast cancer risk in Bangladeshi females.

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Data availability

The datasets during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors express their gratitude to the Pharmacy Discipline of Khulna University, Bangladesh for laboratory facilities. We are thankful to the staff, nurses, physicians, and the authority of the National Institute of Cancer Research and Hospital (NICRH) of Dhaka, Khulna Medical College Hospital. Khulna Bangladesh for their kind permission and assistance to collect blood samples from breast cancer patients and allowing relevant clinical data. We also express our thankful gratitude to the Ministry of Science and Technology of the Government of the People’s Republic of Bangladesh and Khulna University Research Cell for their partial financial support to conduct the study.

Funding

The authors received partial financial support from the Ministry of Science and Technology of the Government of the People’s Republic of Bangladesh and also from Khulna University Research Cell.

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NRH and MMR (Md. Mostafizur Rahman) conceived the presented idea and carried out lab experiments. MMR* and AH developed the theory. SMH and RS contributed to patient identification and blood sample collection. MMR* and RS verified the analytical method. MAM and AH carried out statistical analysis. MMR* supervised the investigation and findings of this work. All authors discussed the results and contributed to the final manuscript. NRH and MMR contributed equally (*, Md. Mustafizur Rahman).

Corresponding author

Correspondence to Md. Mustafizur Rahman.

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The study was conducted according to the Helsinki declaration and its subsequent revisions and the protocol was approved by the Ethical Committee of the hospital.

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Howlader, N.R., Rahman, M.M., Hossain, M.A. et al. Genetic polymorphisms in DNA repair genes XRCC1 and 3 are associated with increased risk of breast cancer in Bangladeshi population. Breast Cancer Res Treat 182, 739–750 (2020). https://doi.org/10.1007/s10549-020-05738-8

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Keywords

  • Breast cancer
  • XRCC1
  • XRCC3
  • Polymorphisms
  • SNP
  • Bangladesh