Polymorphisms in the DNA repair gene XRCC1 and breast cancer (original) (raw)
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Breast Cancer Research, 2005
The gene XRCC1 (X-ray repair crosscomplementing group 1) encodes a protein involved in DNA base excision repair. Two non-synonymous polymorphisms in XRCC1 (Arg194Trp and Arg399Gln) have been shown to alter DNA repair capacity in some studies in vitro. However, results of previous association studies of these two XRCC1 variants and breast cancer have been inconsistent. We examined the association between polymorphisms in XRCC1 and breast cancer in the American Cancer Society Cancer Prevention Study II (CPS-II) Nutrition Cohort, a large prospective study of cancer incidence in the USA.
Cancer Detection and Prevention, 2006
Background: Genetic variation in DNA repair may contribute to differences in the susceptibility of several cancers. We evaluated two polymorphisms in the base excision repair pathway (BER) (XRCC1; Arg194Trp and Arg399Gln) and one polymorphism in the double strand DNA repair pathway (XRCC3; Thr241Met) for their association with breast cancer risk. Methods: The association was analyzed in a nested case control study of 460 breast cancer cases and 324 cancer-free controls within the Iowa Women's Health Cohort. DNA was obtained from blood samples or paraffin embedded tissues (PET) and all samples were genotyped by one of three genotyping platforms-PCR-RFLP, PCR-INVADER, or Sequenom. Results: None of the three polymorphisms studied were significantly associated with breast cancer risk (XRCC1:
Technology in Cancer Research & Treatment
X-ray repair cross complementary group gene is one of the most studied candidate gene involved in different types of cancers. Studies have shown that X-ray repair cross complementary genes are significantly associated with increased risk of breast cancer in females. Moreover, studies have revealed that X-ray repair cross complementary gene polymorphism significantly varies between and within different ethnic groups globally. The present case-control study was aimed to investigate the association of X-ray repair cross complementary 1A (Arg194Trp) and X-ray repair cross complementary 3 (Thr241Met) polymorphism with the risk of breast cancer in females from northeastern region of India. The present case-control study includes histopathologically confirmed and newly diagnosed 464 cases with breast cancer and 534 apparently healthy neighborhood community controls. Information on sociodemographic factors and putative risk factors were collected from each study participant by conducting faceto-face interviews. Genotyping of X-ray repair cross complementary 1A (Arg194Trp) and X-ray repair cross complementary 3 (Thr241Met) was carried out by polymerase chain reaction-restriction fragment length polymorphism. For statistical analysis, both univariate and multivariate logistic regression analyses were performed. We also performed stratified analysis to find out the association of X-ray repair cross complementary genes with the risk of breast cancer stratified based on menstrual status. This study revealed that tryptophan allele (R/W-W/W genotype) in X-ray repair cross complementary 1A (Arg194Trp) gene significantly increased the risk of breast cancer (adjusted odds ratio ¼ 1.44, 95% confidence interval ¼ 1.06-1.97, P < .05 for R/W-W/W genotype). Moreover, it was found that tryptophan allele (W/W genotype) at codon 194 of X-ray repair cross complementary 1A (Arg194Trp) gene significantly increased the risk of breast cancer in premenopausal females (crude odds ratio ¼ 1.66, 95% confidence interval ¼ 1.11-2.46, P < .05 for R/W-W/W genotype). The present study did not reveal any significant association of X-ray repair cross complementary 3 (Thr241Met) polymorphism with the risk of breast cancer. The present study has explored that X-ray repair cross complementary 1A (Arg194Trp) gene polymorphism is significantly associated with the increased risk of breast cancer in premenopausal females from northeastern region of India which may be beneficial for prognostic purposes.
Open Medicine Journal, 2015
The aim of this paper is to analyse the role exerted by X-ray repair cross-complementing group 1 (XRCC1) genetic polymorphisms and haplotypes in increasing breast cancer risk and in modulating radiotherapy-induced adverse reactions. An Italian cohort of breast cancer patients and a matching group of healthy controls were genotyped for XRCC1-77T>C, Arg194Trp and Arg399Gln polymorphisms. Our data indicated that polymorphisms at codon 399 and at -77 position of the 5’-untraslated region both contribute to cancer risk. We also showed that the haplotype H3, containing the wild-type allele at codon 194 and the variant alleles at codon 399 and at -77 position is significantly associated with an increased risk of breast cancer. We found no statistical association between XRCC1 SNPs and individual radiosensitivity.
XRCC1 and XRCC3 DNA repair gene polymorphisms in breast cancer women from the Lodz region of Poland
Polish journal of pathology : official journal of the Polish Society of Pathologists, 2009
Genetic polymorphism in XRCC1 and XRCC3 genes may influence DNA repair capacity and, in turn, confer predisposition to breast cancer. In the present work the distribution of genotypes and frequency of alleles of the Arg194Trp and Arg399Gln polymorphism of XRCC1 and Trp241 Met polymorphism in XRCC3 in breast cancer women were analysed. Blood samples were obtained from 150 women with breast cancer and controls (n = 106). The polymorphisms were determined by PCR-RFLP methods. No association between XRCC1 Arg399Gln and Arg194Trp genotype and breast cancer risk was observed. The distribution of the genotypes of the Trp241 Met polymorphism of XRCC3 in both controls and patients did not differ significantly (p > 0.05) from those predicted by the Hardy-Weinberg distribution. There were no significant differences (p > 0.05) in genotype distributions and allele frequencies between subgroups assigned to histological stage. The results suggest that the Arg194Trp and Arg399Gln polymorphism...
Breast Cancer Research and Treatment, 2008
The DNA repair pathway is known to play a role in the etiology of breast cancer. A number of studies have demonstrated that common germline variants in genes involved in the DNA repair pathway influence breast cancer risk. To assess whether alterations in DNA repair genes contribute to breast cancer, we genotyped 12 single nucleotide polymorphisms (SNPs) in 1,109 Cypriot women with breast cancer and 1,177 age-matched healthy controls. We found significant associations with breast cancer for SNPs in the BRCA2 and MRE11A genes. Carriers of the BRCA2 rs1799944 variant (991 Asp) were found to have an increased risk of breast cancer (OR = 1.41, 95% CI 1.08-1.83, P = 0.01) with P trend = 0.0076. Homozygous carriers of the MRE11A rs601341 A allele had an increased risk of breast cancer (OR = 1.36, 95% CI 1.08-1.71, P = 0.009) with P trend = 0.0087. This study suggests that genetic variants in BRCA2 and MRE11A are associated with breast cancer risk.
XRCC1 genetic polymorphism and breast cancer risk
Pharmacogenetics, 2002
Breast cancer is the second most frequent cancer in Korean women and the incidence is increasing in both Western countries and Korea . Although a substantial proportion of breast cancer cases are explained by well-established risk factors (i.e. later age at first birth, nulliparity and first-degree family history of breast cancer) [3], the reason for the observed worldwide increase in breast cancer incidence is still largely unknown. Recently, inherited differences in the DNA repair capacity were proposed to modify individual susceptibility to cancer.
Genetic Testing and Molecular Biomarkers, 2014
Various DNA damage, induced by endogenous and exogenous factors, is handled through DNA repair pathways such as X-ray repair cross-complementing protein (XRCC). Genetic variations in these pathways may have a joint or additive effect on various types of cancer, including the risk of breast cancer (BC). Aim: To evaluate the association of three single-nucleotide polymorphisms (SNPs) Arg399Gln, Arg194Trp, and Thr241Met in DNA repair genes XRCC1 and XRCC3 on the risk of BC, and to assess their interaction with risk factors and prognostic markers in a case-control study in Egypt. Methods: We detected the studied SNPs using polymerase chain reaction-restriction enzyme polymorphism (PCR-RFLP) in peripheral blood from 100 BC patients and 75 healthy females. Results: The dominant model of inheritance of Arg399Gln and Arg194Thr revealed an increase in BC risk of odds ratio (OR) of 3.56, 95% confidence interval (CI) = 1.22-10.39, p = 0.017 and OR: 4.45, 95% CI = 2.35-8.45, p < 0.001 respectively. However, there was no clear interaction between the studied SNPs and the known risk factors, or tumor criteria. No association between the Thr241Met genotype and BC risk was observed. Conclusion: XRCC1 Arg399Gln and Arg164Trp variant genotypes are associated with an increased risk of BC in Egyptian females.
Polymorphisms of the DNA Repair Gene XRCC1 and Lung Cancer Risk
Cancer Epidemiology Biomarkers Prevention a Publication of the American Association For Cancer Research Cosponsored By the American Society of Preventive Oncology, 2001
We explored the association between polymorphisms of the DNA repair gene XRCC1 (codons 194, 280, and 399) and lung cancer risk in a case-control study nested within a cohort of tin miners. Cases were those diagnosed with lung cancer over 6 years of follow-up (n ؍ 108). Two controls, matched on age and sex, were selected for each case by incidence density sampling. Of the three polymorphisms, only the XRCC1 Arg280His allele was associated with increased lung cancer risk (odds ratio, 1.8; 95% confidence interval, 1.0-3.4) after adjustment for radon and tobacco exposure. In addition, individuals with the variant Arg280His allele who were alcohol drinkers seemed to be at higher risk for lung cancer compared with those with the homozygous wild-type genotype. Conversely, individuals with the variant Arg194Trp allele who were alcohol drinkers seemed to be at lower risk for lung cancer compared with those with the homozygous wild-type genotype. Polymorphisms of XRCC1 appear to influence risk of lung cancer and may modify risk attributable to environmental exposures.