Association of XRCC3, XRCC4, BAX, and BCL-2 Polymorphisms with the Risk of Breast Cancer.

Emre Ozoran,Duygu Erhan,Mehmet Guven,Bahadir Batar,Fadime Didem Can Trabulus,Pranshu Sahgal

doi:10.1155/2022/5817841

Abstract

Background Breast cancer is the most common malignancy in women. Genetic risk factors associated with breast cancer incidence have been identified. Aims This study is aimed at determining the association of XRCC3 Thr241Met (rs861539), XRCC4 G(-1394) T (rs6869366) DNA repair and BAX G(-248) A (rs4645878), and BCL2 C(-938) A (rs2279115) apoptotic gene polymorphisms with breast cancer. Materials and Methods Genetic analysis was performed using peripheral blood samples. Gene polymorphisms were detected by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. 175 patients and 158 healthy controls were enrolled in the study. Results Breast cancer risk was 5.43 times more in individuals with AA genotype of Bax G(-248) A (rs4645878) (P = 0.002). The risk of metastasis was 11 times with this genotype. It was associated with 6 times more risk of having a tumor larger than 2 cm. The risk of breast cancer was 2.77 times more in individuals carrying the Met/Met genotype of XRCC3 Thr241Met (rs861539) (P = 0.009). The risk of having advanced clinical stage (stage III+IV) with the Met/Met genotype was 4 times more increased. No relationship with breast cancer was found with XRCC4 G(-1394) T (rs6869366) and BCL2 C(-938) A (rs2279115) gene polymorphisms. Conclusion Multicenter trials using subjects with genetic variations are needed to establish the relationship between breast cancer and single gene polymorphism.

Highlights

Breast cancer is one of the most common malignancies seen in women and one of the leading reasons of cancer-related mortality in developed countries
The distributions of the Xray repair cross-complementing group 3 (XRCC3) Thr241Met, X-ray cross-complementing group 4 (XRCC4) G (-1394) T, BAX G(-248) A, and BCL2 C(-938) A genotypes were in accordance with the Hardy–Weinberg equilibrium (HWE) among the cases and controls
In the analysis of BAX G(-248) A gene polymorphism, homozygote expression (AA genotype) of BAX-248A allele was associated with 5 times increased risk of breast cancer (OR = 5:43, 95% confidence intervals (CIs) = 1:70–15:84; P = 0:002)

Summary

Introduction

Breast cancer is one of the most common malignancies seen in women and one of the leading reasons of cancer-related mortality in developed countries. Studies have suggested that DNA repair and apoptosis mechanisms could have a role in the development of breast cancer. It has been reported that DNA repair and apoptosis gene polymorphisms could affect breast cancer risk [1, 2]. Epidemiological studies have shown that DNA double-strand breaks are a risk factor in the development of breast cancer [4]. These findings, put the genes responsible for DNA double-strand break repair important candidates for further studies. This study is aimed at determining the association of XRCC3 Thr241Met (rs861539), XRCC4 G (-1394) T (rs6869366) DNA repair and BAX G(-248) A (rs4645878), and BCL2 C(-938) A (rs2279115) apoptotic gene polymorphisms with breast cancer. Multicenter trials using subjects with genetic variations are needed to establish the relationship between breast cancer and single gene polymorphism

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Conclusion