Genetic polymorphisms in DNA repair genes XRCC1 and 3 are associated with increased risk of breast cancer in Bangladeshi population (original) (raw)
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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.
https://www.ijhsr.org/IJHSR\_Vol.7\_Issue.2\_Feb2017/IJHSR\_Abstract.044.html, 2017
Background & Objectives: Breast cancer is a major concern of health risk, moreover the leading cause of cancer causing deaths in women of rural parts of India. In this study, we focused to determine the frequency of polymorphisms in DNA repair genes, XRCC1 at codon (cd) 194, cd 280, cd 399, XRCC 2 at cd 188 and XRCC3 at cd 241 to evaluate their role in breast cancer risk. Methods: We used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to analyze XRCC genes polymorphisms in 150 breast cancer women and 200 age matched disease-free controls. Results: The result from our study showed that allele frequencies of selected genes were not statistically different between the groups for XRCC1 Trp194, Gln399, XRCC2 His188 and XRCC3 Met241. XRCC1 His280 (OR= 4.14; 95% CI= (2.63-6.53); p= <0.0001) genotype significantly increased the risk of breast cancer. Interpretation & conclusions: This study indicates that polymorphisms in cd280 of XRCC1 gene could play a role in modifying genetic susceptibility of individuals towards breast cancer among women from rural Maharashtra. It is apparent from our findings that larger part of the female had age at first delivery lower than 20 years which could be the probable risk factor for development of breast cancer. Thus, the case-control study suggest that selected DNA repair genes represent genetic determinants in breast carcinogenesis along with other risk factors in the rural Indian population.
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.
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.
https://www.ijhsr.org/IJHSR\_Vol.7\_Issue.7\_July2017/IJHSR\_Abstract.040.html, 2017
Breast cancer is a major concern of women health in developing countries, including India. This study was aimed to determine the polymorphisms in DNA repair gene, Xeroderma pigmentosum complementation group D (XPD) at codon (cd) 156, cd199, cd320, cd751 in patients of breast cancer from Maharashtra and to evaluate their association with breast cancer development. Methods: We conducted a case control study including 170 breast cancer cases and 200 hospital based age and sex matched healthy controls to estimate the role of genetic polymorphisms of XPD gene in the context of breast cancer risk for the Maharashtrian population. We used PCR-RFLP to analyze XPD gene polymorphisms. Results: The result from our study showed that allele frequencies of selected genes were not statistically different between the groups for XPD Arg156, XPD Met199, XPD Gln751 except XPD312. XPD Asn312 (OR= 5.14; 95% CI= (3.04-8.69); p= <0.0001) genotype significantly increased the risk of breast cancer. Conclusions: This study indicates that polymorphisms in cd320 of XPD gene could play a role in modifying genetic susceptibility of individual to breast cancer in Maharashtra patients.
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...
Bulletin of Egyptian Society for Physiological Sciences
The genes involved in DNA repair system play a crucial role in the protection against mutations .It has been hypothesized that functional deficiencies in highly conserved DNA repair processes resulting from polymorphic variation may increase genetic susceptibility to breast cancer. There are multiple pathways to repair the different types of DNA damage and maintain genomic integrity among them is the nucleotide excision repair (NER) and the base excision repair (BER) pathways. Aim & methods: The aim of the present study was to examine the relation between the DNA repair gene polymorphisms and breast cancer (BC) risk in Egyptian females and to analyze their relation to clinico-pathological parameters of BC and also to investigate the synergistic effect of both genes on BC susceptibility. Both XPD and XRCC1 polymorphisms were characterized in 100 BC Egyptian females and 100 healthy women who had no history of any malignancy by amplification refractory mutation system-polymerase chain reaction (PCR) (ARMS) method and PCR with confronting two-pair primers(PCR-CTPP) , using DNA from peripheral blood in a case control study. RESULTS: our results revealed that the frequencies of AA genotype of XPD codon 312 polymorphism were significantly higher in the breast cancer study patients than in the normal individuals(p≤0.003), and did not observe any association between the XRCC1 Arg399Gln polymorphism and risk of developing breast cancer Also, no association between both XPD Asp312Asn and XRCC1 A399G polymorphisms and the clinical characteristics of disease Finally ,the combination of AA(XPD)+AG(XRCC1) were significantly associated with breast cancer risk. In conclusion, the present results suggest that, XPD gene is an important candidate gene for susceptibility to breast cancer. Also, gene-gene interaction between XPD(AA)+XRCC1(AG) polymorphism may be associated with increased risk of breast cancer in Egyptian women.
The XRCC3 Thr241Met polymorphism and breast cancer risk: a case–control study in a Thai population
Biomarkers, 2007
The X-ray repair cross-complementing group 3 gene (XRCC3 ) belongs to a family of genes responsible for repairing DNA double-strand breaks caused by normal metabolic processes and exposure to ionizing radiation. Polymorphisms in DNA repair genes may alter an individual's capacity to repair damaged DNA and may lead to genetic instability and contribute to malignant transformation. We examined the role of a polymorphism in the XRCC3 gene (rs861529; codon 241: threonine to methionine change) in determining breast cancer risk in Thai women. The study population consisted of 507 breast cancer cases and 425 healthy women. The polymorphism was analysed by fluorescence-based melting curve analysis. The XRCC3 241Met allele was found to be uncommon in the Thai population (frequency 0.07 among cases and 0.05 among controls). Odds ratios (OR) adjusted for age, body mass index, age at menarche, family history of breast cancer, menopausal status, reproduction parameters, use of contraceptives, tobacco smoking, involuntary tobacco smoking, alcohol drinking, and education were calculated for the entire population as well as for pre-and postmenopausal women. There was a significant association between 241Met carrier status and breast cancer risk (OR 1.58, 95% confidence interval (CI) 1.02 Á2.44). Among postmenopausal women, a slightly higher OR (1.82, 95% CI 0.95 Á3.51) was found than among premenopausal women (OR 1.48, 95% CI 0.82 Á2.69). Our findings suggest that the XRCC3 Thr241Met polymorphism is likely to play a modifying role in the individual susceptibility to breast cancer among Thai women as already shown for women of European ancestry.
Background: Sporadic breast cancer might be caused by low-penetrance genes, including genes constituting the DNA repair pathways. Defective DNA repair is a common imprint of cancer that promotes the accretion of DNA errors and genomic instability. The clustering of damage in DNA may stimulate breast carcinogenesis. Aims: The goal of the study is to evaluate the role of single nucleotide polymorphisms in DNA repair genes XRCC1 Arg399Gln, XPD Lys751Gln, RAD51 G135C and XRCC3 Thr241Met as genetic indicators of susceptibility to breast cancer and to evaluate their role in treatment outcome. Methodology: The study included 248 females diagnosed with primary breast cancer and 232 normal healthy females. Patients were clinically followed up for 5 years after completing chemotherapy. Genomic DNA was isolated and the four polymorphisms under investigation were assessed by PCR-RFLP technique. Findings: XRCC1 399Gln, XPD 751Gln and XRCC3 241Met alleles were significantly associated with breast cancer risk (OR = 2.63, 2.17 and 3.21; respectively), with carriers having lower disease free survival (DSF). When grouping patients based on the number of affected genotypes they carry, DFS decreased as the number of affected genotypes increased (P accum <0.001), patients carrying three (HR=4.74, p<0.001) or two (HR=3.35, p=0.005) affected genotypes had significantly worse DFS compared with those carrying zero (reference) or one (HR=1.37, p=0.093) affected genotype. RAD51 5'UTR G135C polymorphism was not associated with breast cancer risk (p=0.932) or with DFS. Conclusion: XRCC1 Arg399Gln, XPD Lys751Gln and XRCC3 Thr241Met polymorphisms may take a significant part in sporadic breast cancer as risk factors and in prognosis, where patients carrying XRCC1 Arg/Arg, XPD Lys/Lys and XRCC3 Thr/Thr genotypes had significantly diminished risk for breast cancer and higher DFS. DFS decreased as the number of affected genotypes increased. But RAD51 5'UTR G135C polymorphism did not associate with either risk or prognosis of breast cancer.
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...