Association of the Arg194Trp and the Arg399Gln Polymorphisms of the XRCC1 Gene With Risk Occurrence and the Response to Adjuvant Therapy Among Polish Women With Breast Cancer

BackgroundConverging evidence supports the central role of DNA damage in progression to breast cancer. We therefore in this study aimed to assess the potential interactions of seven common polymorphisms from five DNA repair genes (XRCC1, XRCC2, XRCC3, XPA and APEX1) in association with breast cancer among Han Chinese women.Methodology/Principal FindingsThis was a case-control study involving 606 patients diagnosed with sporadic breast cancer and 633 age- and ethnicity-matched cancer-free controls. The polymerase chain reaction - ligase detection reaction method was used to determine genotypes. All seven polymorphisms were in accordance with Hardy-Weinberg equilibrium in controls. Differences in the genotypes and alleles of XRCC1 gene rs25487 and XPA gene rs1800975 were statistically significant between patients and controls, even after the Bonferroni correction (P<0.05/7). Accordingly, the risk for breast cancer was remarkably increased for rs25487 (OR = 1.28; 95% CI: 1.07–1.51; P = 0.006), but decreased for rs1800975 (OR = 0.77; 95% CI: 0.67–0.90; P = 0.001) under an additive model at a Bonferroni corrected alpha of 0.05/7. Allele combination analysis showed higher frequencies of the most common combination C-G-G-C-G-G-G (alleles in order of rs1799782, rs25487, rs3218536, rs861539, rs1800975, rs1760944 and rs1130409) in controls than in patients (PSim = 0.002). In further interaction analysis, two-locus model including rs1800975 and rs25487 was deemed as the overall best model with the maximal testing accuracy of 0.654 and the cross-validation consistency of 10 out of 10 (P = 0.001).ConclusionOur findings provide clear evidence that XRCC1 gene rs25487 and XPA gene rs1800975 might exert both independent and interactive effects on the development of breast cancer among northern Chinese women.

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“…The selection of these functional polymorphisms was based on their wide evaluation in association with various forms of cancer [9]–[15].…”

Section: Methodsmentioning

confidence: 99%

The Relationship between Seven Common Polymorphisms from Five DNA Repair Genes and the Risk for Breast Cancer in Northern Chinese Women

et al. 2014

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“…Numerous mutations in XRCC1 have been reported to interrupt the protein function by altering binding sites or catalytic domain of the protein (Caldecott, 2003). The 194Trp codon of XRCC1 is located in a highly conserved hydrophobic linker region between its DNA polymerase β domain and poly (ADP-ribose) polymerase-interacting domains, so the change from arginine to tryptophan could alter theinteraction of XRCC1 with either or both of these DNA repair proteins within the base excision repair complex (Przybylowska-Sygut et al, (2013). The Arg399Gln polymorphism alters Arginine to Glutamine substitution at codon 399 of exon 10 (C>T, rs25487) and is located in the conserved residue of the poly (ADP-ribose) polymerase-binding domain of XRCC1 (Pramanik et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Association of XRCC1 Gene Polymorphisms with Breast Cancer Susceptibility in Saudi Patients

Mutairi¹,

Alanazi²,

Shalaby³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Background: X-ray repair cross-complementing group 1 (XRCC1) plays a key role in the base excision repair pathway, as a scaffold protein that brings together proteins of the DNA repair complex. XRCC1 is reported to be a candidate influence on cancer risk. The aim of our present study was to assess the association of rs1799782 (Arg194Trp) and rs25487 (Arg399Gln) XRCC1 gene polymorphisms with breast cancer in the Saudi population. Materials and Methods: The two SNP's were analyzed in breast cancer patients and healthy control subjects. Genotypes were determined by TaqMan SNP genotype analysis technique and data were analyzed using Chisquare or t test and logistic regression analysis by SPSS16.0 software. Results and Conclusions: Results showed that rs1799782 significantly increased susceptibility to breast cancer with Arg/Trp, Arg/Trp+Trp/Trp genotypes and at Trp allele overall study. It also increased risk of breast cancer in older age patients (above 48) and with the ER positive category. XRCC1rs25487 (Arg399Gln) did not showed any significant association. In conclusion the XRCC1rs1799782 polymorphism may be involved in the etiology of breast cancer in the Saudi population. Confirmation of our findings in larger populations of different ethnicities is warranted.

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“…Despite many studies showed no association between breast cancer and XRCC1 gene polymorphisms (Thyagarajan et al, 2006;Smith et al, 2008;Liu et al, 2011b), some demonstrated increase in risk of breast cancer (Przybylowska-Sygut et al, 2013a;Shadrina et al, 2014b) or even decrease of breast cancer risk (Patel et al, 2005a).…”

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confidence: 99%

XRCC1 Gene Polymorphisms and Breast Cancer Risk: A Systematic Review and Meta-analysis Study

Moghaddam

Nazarzadeh²,

Moghaddam³

et al. 2016

Asian Pacific Journal of Cancer Prevention

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Association of the Arg194Trp and the Arg399Gln Polymorphisms of the XRCC1 Gene With Risk Occurrence and the Response to Adjuvant Therapy Among Polish Women With Breast Cancer

Abstract: We suggest that the polymorphism of the XRCC1 gene may be considered a predictive factor associated with the risk of occurrence and the survival outcome in breast cancer among Polish women.

Cited by 26 publications

References 55 publications

The Relationship between Seven Common Polymorphisms from Five DNA Repair Genes and the Risk for Breast Cancer in Northern Chinese Women

The Relationship between Seven Common Polymorphisms from Five DNA Repair Genes and the Risk for Breast Cancer in Northern Chinese Women

Association of XRCC1 Gene Polymorphisms with Breast Cancer Susceptibility in Saudi Patients

XRCC1 Gene Polymorphisms and Breast Cancer Risk: A Systematic Review and Meta-analysis Study

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