A prospective study of XRCC1 (X-ray cross-complementing group 1) polymorphisms and breast cancer risk (original) (raw)
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Polymorphisms in the DNA repair gene XRCC1 and breast cancer
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2001
X-ray repair cross complementing group 1 (XRCC1) encodes a protein involved in base excision repair. We examined the association of polymorphisms in XRCC1 (codon 194 Arg-->Trp and codon 399 Arg-->Gln) and breast cancer in the Carolina Breast Cancer Study, a population-based case-control study in North Carolina. No association was observed between XRCC1 codon 194 genotype and breast cancer, and odds ratios (ORs) were not modified by smoking or radiation exposure. A positive association for XRCC1 codon 399 Arg/Gln or Gln/Gln genotypes compared with Arg/Arg was found among African Americans (253 cases, 266 controls; OR = 1.7, 95% confidence interval, 1.1-2.4) but not whites (386 cases, 381 controls; OR =1.0, 95% confidence interval, 0.8-1.4). Among African-American women, ORs for the duration of smoking were elevated among women with XRCC1 codon 399 Arg/Arg genotype (trend test; P < 0.001) but not Arg/Gln or Gln/Gln (P = 0.23). There was no difference in OR for smoking accordi...
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:
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.
XRCC1 gene polymorphisms and breast cancer risk in different populations: A meta-analysis
The Breast, 2009
We performed a meta-analysis to investigate the role of XRCC1 polymorphisms Arg194Trp, Arg280His and Arg399Gln in breast cancer. The results were pooled in a manner that appropriately reflects a biological model of gene effect using a random effects logistic regression model without multiple comparisons. Forty studies from 31 reports were included with 10 465 cases and 10 888 controls at Arg194Trp, 6156 cases and 5806 controls at Arg280His, and 21 467 cases and 22 766 controls at Arg399Gln. Our analysis found a tendency towards a recessive effect of Arg280His variant in Asian population only (His/His vs. Arg/Arg þ Arg/His: OR ¼ 2.27, 95% CI ¼ 0.82, 6.31). An increased breast cancer risk with a recessive effect was also suggested for Arg399Gln variant in Asian population (Gln/Gln vs. Arg/Arg þ Arg/Gln: OR ¼ 1.59, 95% CI ¼ 1.22, 2.09) only. These findings suggest that polymorphisms Arg280His and Arg399Gln may modify breast cancer risk differently in Caucasian and Asian populations.
Menopausal age and XRCC1 gene polymorphisms: Role in breast cancer risk
Cancer Detection and Prevention, 2007
Background: Recent evidence that some DNA-repair functions are haploinsufficient adds weight to the notion that variants in DNA-repair genes constitute part of the spectrum of defects contributing to cancer risk. X-ray repair cross-complementing group 1 gene (XRCC1) is involved in base excision repair (BER) pathway, acting on spontaneous and induced DNA damage. This gene encodes for a scaffolding protein that brings together different proteins involved in the repair process. Among the non-synonymous polymorphisms in XRCC1 gene, codons 194 and 399 lead to amino acid changes at evolutionary conserved regions, and seem to alter the efficiency of the protein. Methods: A hospital based case-control study was carried out in a Caucasian Portuguese population (241 cancer patients and 457 controls matched for sex and age) in order to evaluate the potential modifying role of the XRCC1 polymorphisms on the individual susceptibility to breast cancer. Results: Our data did not reveal a positive association between the polymorphisms individually and breast cancer, or with the combination of the different genotypic associations. However, after stratification to the menopausal status, it was observed that carriers of the Gln/Gln genotype of the R399Q polymorphism with a menopausal age above 55 years are at increased risk for breast cancer (OR = 4.074; CI = 1.562-10.626; P = 0.004). Concerning the Arg194Trp polymorphism, after stratification by menopausal status, it was observed that heterozygous individuals (Arg/Trp) with a menopausal age between 45 and 54 are at increased risk for breast cancer (adjusted OR = 1.964; CI = 1.174-3.288; P = 0.01) as well as carriers of the variant allele (Arg/Trp + Trp/Trp) (adjusted OR = 1.932; CI = 1.156-3.228; P = 0.012). Conclusions: Our results suggest that menopausal age together with Arg194Trp and Arg399Gln XRCC1 gene polymorphisms might be involved in individual susceptibility to breast cancer. #
Genetika, 2020
Genetic changes in DNA repair genes, such as X-ray cross-complementing group1 (XRCC1), can cause modifications in the capacity of damaged DNA repair and affect the risk of cancer. Several mutations in TP53, which is a tumor suppressor gene, have been associated with breast cancer. In this study, it is aimed to evaluate the association of genetic variation in XRCC1rs25487 single nucleotide polymorphism (SNP) with TP53 mutation and breast cancer risk. In this research, 200 breast cancer women and 200 controls from the Iranian-Azeri population, Iran, were enrolled. Genomic DNA was extracted from the whole blood of controls patients. PCR-RFLP was carried out to genotype all participants for XRCC1rs25487SNP. Determination of possible mutations of TP53 in exons 5,6,7, and 8 were performed on 30 cancerous breast tissues through sequencing the amplified fragments. Our results of the case-control study indicated that the GA genotype of XRCC1 gene in rs25487polymorphism has a significantly ri...
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.
Association of the XRCC1 gene polymorphisms with cancer risk in Turkish breast cancer patients
Experimental & Molecular Medicine, 2004
Abbreviations: BRCA1, Breast cancer-associated gene 1; BRCT-1, BRCA1 C terminus repeat 1; CI, Confidence interval; OR, Odds ratio; XRCC1, X-ray repair cross-complementing group 1 A bstract The X-ray repair cross-com plem enting group 1 (XRCC1) gene is believed to play an im portant role in base excision repair and displays genetic polym orphism s. Data on the role of XRCC1 polym orphism s in cancer susceptibility is inconsistent. In the present study, w e investigated the effect of tw o XRCC1 polym orphism s, Arg194Trp and Arg399G ln, on breast cancer risk in a casecontrol study involving Turkish breast cancer patients and healthy wom en. Both alleles exhibited a sim ilar distribution am ong cases and controls leading to lack of any significant association betw een the XRCC1 polym orphism s and breast cancer risk, either in hom ozygotes and heterozygotes or com bined. The allele frequency of the codon 194 variant w as very low in cases and healthy individuals (5.3 and 3.9% , respectively) com pared to that of the variant 399Gln allele (39.7 and 37.4%). O ur results do not support evidence for a role of the XRCC1 polym orphism in developing breast cancer.
Association of XRCC1 gene polymorphisms with breast cancer susceptibility in Saudi patients
Asian Pacific journal of cancer prevention : APJCP, 2013
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. 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 Chi- square or t test and logistic regression analysis by SPSS16.0 software. 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 sig...