Polymorphism of DNA repair genes in breast cancer

Abstract

AimThe aim of the study was to determine the relationship between single nucleotide polymorphisms (SNPs) of DNA repair genes and modulation of the risk of breast cancer. The following SNPs were analysed: XRCC1-Arg399Gln (rs25487), hMSH2-Gly322Asp (rs4987188), XRCC2-Arg188His (rs3218536), XPD- Lys751Gln (rs13181), RAD51--4719A/T (rs2619679) and RAD51--4601A/G (rs5030789).Material and MethodsThe study included n = 600 patients: 300 with breast cancer and 300 healthy controls. The HRM (High-Resolution Melter) technique was applied for polymorphism analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each genotype and allele.ResultsStatistically significant correlations were identified between four single nucleotide polymorphisms and the breast cancer risk: XRCC1-Arg399Gln, hMSH2-Gly322Asp, XPD- Lys751Gln and RAD51--4719A/T. Allele XRCC1-Gln (OR 6.37; 95% CI 4.86–8.35, p < .0001), hMSH2-Asp (OR 4.41; 95% CI 3.43–5.67, p < .0001), XPD -Gln (OR 2.56; 95% CI 2.02–3.25, p < .0001) and RAD51-T genes (OR 1.44; 95% CI 1.15–1.80, p = 0.002) strongly correlated with breast carcinoma. No relationship was observed between the studied polymorphisms and the cancer progression grade according to Scarf-Bloom-Richardson classification.ConclusionsThe results implies that polymorphisms of DNA repair genes may be associated with breast cancer occurrence.

Risk Modulation of Oral Pre Cancer and Cancer with Polymorphisms in XPD and XPG Genes in North Indian Population

“…Similarly, we have also observed that once oral cancer is established the C allele enhanced the risk of having high stage malignant disease with nodal involvement. Several other cases have reported the link of XPD A/C polymorphism with the development of different cancer in different population indicates its universal role in carcinogenesis (Du et al, 2016;Smolarz et al, 2019;Avci et al, 2018;Zhu et al, 2018).…”

MTHFR, XRCC1 and OGG1 genetic polymorphisms in breast cancer: a case-control study in a population from North Sardinia

“…While the Gln allele of rs25487 leads to a reduction in BER DNA repair activity [24]. Also in this case, the results about the frequency of genotypes of XRCC1-rs1799782 (Arg to Trp) and rs25487 (Arg to Gln) and the BC susceptibility are contrasting [21,[68][69][70][71][72][73][74][75][76][77]. In our study, the XRCC1-rs25487 polymorphism is nominally associated with family history of BC in two genetic models.…”

DNA repair in cancer initiation, progression, and therapy—a double-edged sword

“…The impact of polymorphic DNA repair genes participating in excision repair was studied in various cancer types. A large study by Smolarz et al (2019), analyzing the distribution of XRCC1 , XRCC2 , XPD , and RAD5 1 gene variants in 300 breast cancer patients and 300 controls, did not observe an association between variants determining poor DNA repair potential with cancer progression. However, one of the mentioned genes, namely XRCC1 , was taken under study in the same cancer ( n = 118) but with respect to the other polymorphic site.…”

“…Studies on genetic polymorphism in genes involved in different mechanisms of DNA repair became very productive in discovering potential DNA repair deficit followed by therapy failure. The statement is applicable both to classical genotyping (Alberg et al 2013; Smolarz et al 2019) and to modern biotechnology and bioinformatics (Knijnenburg et al 2018) Further, this is a way for individualizing therapeutic attempts. Literature survey indicates that variability of response to chemotherapy could be expected in any cancer type.…”