DNA Repair Gene XRCC1 and XPD Polymorphisms and Gastric Cancer Risk: A Case-Control Study Outcome from Kashmir, India.
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ABSTRACT:
SUBMITTER: Nissar B
PROVIDER: S-EPMC6129361 | biostudies-literature | 2018
REPOSITORIES: biostudies-literature
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Project description:PURPOSE: The present study was designed to determine the association of polymorphisms of the DNA repair genes X-ray cross-complementing group 1 (XRCC1) (c.1316G>A [rs25487]) and xeroderma pigmentosum complementation group D (XPD) (c.2298A>C [rs13181]) with primary open-angle glaucoma (POAG) and primary closed-angle glaucoma (PCAG). METHODS: In this prospective case-control study, polymerase chain reaction-restriction fragment length polymorphism analysis was used to study the association of XRCC1 and XPD with 160 POAG patients, 163 PCAG patients, and 193 unaffected controls. RESULTS: XRCC1 rs25487 was found to be significantly associated specifically with male POAG patients (?(2) = 13.2 [p = 0.001]), only for the dominant model (odds ratio [OR] = 2.65 [95% confidence interval [CI] = 1.44-4.85], p < 0.005). In addition XPD rs13181 was also found to be associated with male POAG patients (?(2) = 12.1 [p < 0.005]), for both dominant (OR = 2.44 [95% CI = 1.33-4.47], p < 0.005) as well as recessive model (OR = 3.62 [95% CI = 1.45-9.01], p < 0.01). Combined genotypes of both the genes revealed that the heterozygote AC/GA was significantly associated with the male POAG patients (z = 3.00 [p < 0.001]). The AA/GG genotype was present at a higher frequency in the male controls and the AA/GA in the female controls and could thus have a protective role in males and females, respectively. CONCLUSIONS: We postulate that defects in the DNA repair genes XRCC1 and XPD may possibly be associated with the progression of POAG in male patients of Pakistani origin.
| S-EPMC3102023 | biostudies-literature
Project description:Genetic polymorphisms in DNA repair genes may influence individual variation in DNA repair capacity, which may be associated with risk of developing cancer. For colorectal cancer the importance of mutations in mismatch repair genes has been extensively documented. Less is known about other DNA repair pathways in colorectal carcinogenesis. In this study we have focused on the XRCC1, XRCC3 and XPD genes, involved in base excision repair, homologous recombinational repair and nucleotide excision repair, respectively.We used a case-control study design (157 carcinomas, 983 adenomas and 399 controls) to test the association between five polymorphisms in these DNA repair genes (XRCC1 Arg194Trp, Arg280His, Arg399Gln, XRCC3 Thr241Met and XPD Lys751Gln), and risk of colorectal adenomas and carcinomas in a Norwegian cohort. Odds ratio (OR) and 95% confidence interval (95% CI) were estimated by binary logistic regression model adjusting for age, gender, cigarette smoking and alcohol consumption.The XRCC1 280His allele was associated with an increased risk of adenomas (OR 2.30, 95% CI 1.19-4.46). The XRCC1 399Gln allele was associated with a reduction of risk of high-risk adenomas (OR 0.62, 95% CI 0.41-0.96). Carriers of the variant XPD 751Gln allele had an increased risk of low-risk adenomas (OR 1.40, 95% CI 1.03-1.89), while no association was found with risk of carcinomas.Our results suggest an increased risk for advanced colorectal neoplasia in individuals with the XRCC1 Arg280His polymorphism and a reduced risk associated with the XRCC1 Arg399Gln polymorphism. Interestingly, individuals with the XPD Lys751Gln polymorphism had an increased risk of low-risk adenomas. This may suggest a role in regression of adenomas.
| S-EPMC1458350 | biostudies-literature
Project description:The carcinogenic chemicals and reactive oxygen species in tobacco can result in DNA damage. DNA repair genes play an important role in maintaining genome integrity. Genetic polymorphisms of DNA repair genes and smoking may contribute to susceptibility of lung cancer.In this hospital-based case-control study, we investigated the relationship between 13 tagging single nucleotide polymorphisms (SNPs) in base excision repair pathway and nucleotide excision repair pathway genes, smoking, and lung cancer susceptibility. Thirteen tag SNPs were genotyped in 265 lung cancer patients and 301 healthy controls. Logistic regression and multifactor dimensionality reduction method were applied to explore the association and high-order gene-gene and gene-smoking interaction.In single tag SNP analysis, XPA rs2808668, XPC rs2733533, and XPD rs1799787 were significantly associated with lung cancer susceptibility. Joint effects analysis of XPA rs2808668, XPC rs2733533 and XPD rs1799787 showed that there was an increased risk of lung cancer with increasing numbers of risk alleles. Haplotype analysis showed that XRCC1 (rs25487, rs1799782, rs3213334) GCC had a positive association with lung cancer. Analysis of gene-gene and gene-smoking interaction by multifactor dimensionality reduction showed that a positive interaction existed between the four genes and smoking. The two-factor model, including XPC rs2755333 and smoking, had the best prediction ability for lung cancer. Compared with the C/C genotype of XPC rs2733533 and no smoking, the combination of genotype A carriers with XPC rs2733533 and heavy smokers (?30 pack-year) had a 13.32-fold risk of lung cancer.Our results suggest multiple genetic variants in multiple DNA repair genes may jointly contribute to lung cancer risk through gene-gene and gene-smoking interactions.
| S-EPMC4704308 | biostudies-literature
Project description:Variations in genes involved in DNA repair systems have been proposed as risk factors for the development of preeclampsia (PE). We conducted a case-control study to investigate the association of Human apurinic/apyrimidinic (AP) endonuclease (APEX1) Asp148Glu (rs1130409), Xeroderma Pigmentosum group D (XPD) Lys751Gln (rs13181), X-ray repair cross-complementing group 1 (XRCC) Arg399Gln (rs25487) and X-ray repair cross-complementing group 3 (XRCC3) Thr241Met (rs861539) polymorphisms with PE in a Mexican population. Samples of 202 cases and 350 controls were genotyped using RTPCR. Association analyses based on a ?2 test and binary logistic regression were performed to determine the odds ratio (OR) and a 95% confidence interval (95% CI) for each polymorphism. The allelic frequencies of APEX1 Asp148Glu polymorphism showed statistical significant differences between preeclamptic and normal women (p = 0.036). Although neither of the polymorphisms proved to be a risk factor for the disease, the APEX1 Asp148Glu polymorphism showed a tendency of association (OR: 1.74, 95% CI = 0.96-3.14) and a significant trend (p for trend = 0.048). A subgroup analyses revealed differences in the allelic frequencies of APEX1 Asp148Glu polymorphism between women with mild preeclampsia and severe preeclampsia (p = 0.035). In conclusion, our results reveal no association between XPD Lys751Gln, XRCC Arg399Gln and XRCC3 Thr241Met polymorphisms and the risk of PE in a Mexican mestizo population; however, the results in the APEX1 Asp148Glu polymorphism suggest the need for future studies using a larger sample size.
| S-EPMC3975397 | biostudies-literature
Project description:BackgroundPolymorphisms in DNA repair genes have been associated to repair DNA lesions, and might contribute to the individual susceptibility to develop different types of cancer. Nucleotide excision repair (NER), base excision repair (BER), and double-strand break repair (DSBR) are the main DNA repair pathways. We investigated the relationship between polymorphisms in two NER genes, XPC (poly (AT) insertion/deletion: PAT-/+) and XPD (Asp312Asn and Lys751Gln), the BER gene XRCC1 (Arg399Gln), and the DSBR gene XRCC3 (Thr241Met) and the risk of developing lung cancer.MethodsA hospital-based case-control study was designed with 516 lung cancer patients and 533 control subjects, matched on ethnicity, age, and gender. Genotypes were determined by PCR-RFLP and the results were analysed using multivariate unconditional logistic regression, adjusting for age, gender and pack-years.ResultsBorderline association was found for XPC and XPD NER genes polymorphisms, while no association was observed for polymorphisms in BER and DSBR genes. XPC PAT+/+ genotype was associated with no statistically significant increased risk among ever smokers (OR = 1.40; 95%CI = 0.94-2.08), squamous cell carcinoma (OR = 1.44; 95%CI = 0.85-2.44), and adenocarcinoma (OR = 1.72; 95%CI = 0.97-3.04). XPD variant genotypes (312Asn/Asn and 751Gln/Gln) presented a not statistically significant risk of developing lung cancer (OR = 1.52; 95%CI = 0.91-2.51; OR = 1.38; 95%CI = 0.85-2.25, respectively), especially among ever smokers (OR = 1.58; 95%CI = 0.96-2.60), heavy smokers (OR = 2.07; 95%CI = 0.74-5.75), and adenocarcinoma (OR = 1.88; 95%CI = 0.97-3.63). On the other hand, individuals homozygous for the XRCC1 399Gln allele presented no risk of developing lung cancer (OR = 0.87; 95%CI = 0.57-1.31) except for individuals carriers of 399Gln/Gln genotype and without family history of cancer (OR = 0.57; 95%CI = 0.33-0.98) and no association was found between XRCC3 Thr241Met polymorphism and lung cancer risk (OR = 0.92; 95%CI = 0.56-1.50), except for the 241Met/Met genotype and squamous cell carcinoma risk (OR = 0.47; 95%CI = 0.23-1.00).ConclusionIn conclusion, we analysed the association between XPC, XPD, XRCC1, and XRCC3 polymorphisms and the individual susceptibility to develop lung cancer in the Spanish population, specifically with a highly tobacco exposed population. We attempt to contribute to the discovery of which biomarkers of DNA repair capacity are useful for screening this high-risk population for primary preventing and early detection of lung cancer.
| S-EPMC2020474 | biostudies-literature
Project description:OBJECTIVE: This meta-analysis aimed to determine the relationships between XRCC1 Arg399Gln (rs25487 G>A) and XPD Lys751Gln (rs1052559 A>C) polymorphisms and susceptibility to age-related cataract. METHODS: Medline (1966-2013), the Cochrane Library Database (Issue 12, 2013), EMBASE (1980-2013), CINAHL (1982-2013), Web of Science (1945-2013) and the Chinese Biomedical Database (CBM; 1982-2013) were searched without language restrictions. Various combinations of the keywords and MeSH terms were used to screen for potentially relevant studies, specifically "genetic polymorphisms" or "SNPs" or "variation" or "single nucleotide polymorphism" or "polymorphism" or "mutation" or "variant"; "X-ray repair cross complementing protein 1" or "Xeroderma Pigmentosum Group D Protein" or "X-ray repair cross complementing protein 1" or "Xeroderma Pigmentosum Group D Protein" or "XPD" or "Xeroderma Pigmentosum Complementation Group D Protein" or "ERCC2" or "XRCC1" or "XRCC1 DNA repair protein"; and "Cataract" or " Membranous Cataract" or " Pseudoaphakia." Meta-analyses were conducted using Stata 12.0 software. Crude odds ratios (ORs) and their corresponding 95% confidence intervals (95% CI) were calculated. RESULTS: Six independent case-control studies were included in the meta-analysis. Our results indicated that the association between the genetic polymorphisms of XRCC1 Arg399Gln G>A and XPD Lys751Gln A>C and increased susceptibility to age-related cataracts was statistically significant (XRCC1 Arg399Gln: OR=1.30, 95% CI=1.17-1.44, p<0.001; XPD Lys751Gln: OR=1.25, 95% CI=1.12-1.40, p<0.001, respectively). Ethnicity-stratified analysis indicated that the XRCC1 Arg399Gln G>A polymorphism was correlated with the development and progression of age-related cataract in China, India, and Turkey in the allele model and the dominant model. For the XPD Lys751Gln A>C variant, the association with the pathogenesis of age-related cataract in China and Turkey in the allele model and the dominant model was investigated. CONCLUSIONS: The association of XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms with age-related cataract susceptibility observed in our meta-analyses supports the view that XRCC1 and XPD may play important roles in susceptibility to age-related cataract.
| S-EPMC4384174 | biostudies-literature
Project description:Cigarette smoking and chemical occupational exposure are the main known risk factors for bladder transitional cell carcinoma (TCC). Oxidative DNA damage induced by carcinogens present in these exposures requires accurate base excision repair (BER). The XRCC1 protein plays a crucial role in BER by acting as a scaffold for other BER enzymes. Variants in the XRCC1 gene might alter protein structure or function or create alternatively spliced proteins which may influence BER efficiency and hence affect individual susceptibility to bladder cancer. Recent epidemiological studies have shown inconsistent associations between these polymorphisms and bladder cancer. To clarify the situation, we conducted a comprehensive analysis of 14 XRCC1 polymorphisms in a case-control study involving more than 1100 subjects.We found no evidence of an association between any of the 14 XRCC1 polymorphisms and bladder cancer risk. However, we found carriage of the variant Arg280His allele to be marginally associated with increased bladder cancer risk compared to the wild-type genotype (adjusted odds ratio [95% confidence interval], 1.50 [0.98-2.28], p = 0.06). The association was stronger for current smokers such that individuals carrying the variant 280His allele had a two to three-fold increased risk of bladder cancer compared to those carrying the wildtype genotype (p = 0.09). However, the evidence for gene-environment interaction was not statistically significant (p = 0.45).We provide no evidence of an association between polymorphisms in XRCC1 and bladder cancer risk, although our study had only limited power to detect the association for low frequency variants, such as Arg280His.
| S-EPMC1865553 | biostudies-literature
Project description:Neuroblastoma is a lethal tumor that commonly occurs in children. Polymorphisms in XPD reportedly influence risk for several types of cancer, though their roles in neuroblastoma remain unclear. Here we endeavored to determine the relevance of XPD gene polymorphisms and neuroblastoma susceptibility in Chinese children genotyping three XPD polymorphisms (rs3810366, rs13181 and rs238406) in 505 cases and 1070 controls and assessing their contributions to neuroblastoma risk. Overall, we detected no significant association between any single XPD genotype and neuroblastoma risk. When risk genotypes were combined, however, we found that patients with 2-3 risk genotypes were more likely to develop neuroblastoma (adjusted odds ratio =1.31; 95% confidence interval =1.06-1.62, P=0.013) than those with 0-1 risk genotypes. Stratification analysis of rs3810366 revealed significant relationships between the subgroups age ?18 months and clinical stage I+II+4s and neuroblastoma risk. Moreover, the presence of 2-3 risk genotypes was significantly associated with increased neuroblastoma risk in the subgroups age ?18 months, male, tumor originated from others, and clinical stage I+II+4s. Our findings provide novel insight into the genetic underpinnings of neuroblastoma and demonstrate that XPD polymorphisms may have a cumulative effect on neuroblastoma risk.
| S-EPMC6128416 | biostudies-literature
Project description:BackgroundX-ray repair cross-complementing group 1 (XRCC1) is one of the DNA repair genes encoding a scaffolding protein that participate in base excision repair (BER) pathway. However, studies on the association between polymorphisms in this gene and glioma have yielded conflicting results. This meta-analysis was performed to derive a more precise estimation between XRCC1 polymorphisms (Arg399Gln, Arg194Trp, and Arg280His) and glioma risk.MethodsData were collected from several electronic databases, with the last search up to November 28, 2012. Meta-analysis was performed by critically reviewing 9 studies for Arg399Gln polymorphism (3146 cases and 4296 controls), 4 studies for Arg194Trp polymorphism (2557 cases and 4347 controls), and 4 studies for Arg280His polymorphism (1936 cases and 2895 controls). All of the statistical analyses were performed using the software programs STATA (version 11.0).ResultsThe combined results showed that Arg399Gln polymorphism was significantly associated with glioma risk (Gln/Gln versus Arg/Arg: OR?=?1.52, 95% CI?=?1.03-2.23; recessive model: OR?=?1.32, 95% CI?=?1.01-1.73; additive model: OR?=?1.21, 95% CI?=?1.00-1.47), whereas Arg194Trp/Arg280His polymorphisms were all not significantly associated with glioma risk. As for ethnicity, Arg399Gln polymorphism was associated with increased risk of glioma among Asians (Gln/Gln versus Arg/Arg: OR?=?1.78, 95% CI?=?1.29-2.47; Arg/Gln versus Arg/Arg: OR?=?1.28, 95% CI?=?1.05-1.56; recessive model: OR?=?1.59, 95% CI?=?1.16-2.17; dominant model: OR?=?1.36, 95% CI?=?1.13-1.65; additive model: OR?=?1.32, 95% CI?=?1.15-1.52), but not among Caucasians. Stratified analyses by histological subtype indicated that the Gln allele of Arg399Gln polymorphism showed borderline association with the risk of glioblastoma among Caucasians. However, no evidence was observed in subgroup analyses for Arg194Trp/Arg280His polymorphisms.ConclusionsOur meta-analysis suggested that Arg399Gln polymorphism was associated with increased risk of glioma among Asians and borderline increased risk for glioblastoma among Caucasians, whereas Arg194Trp/Arg280His polymorphisms might have no influence on the susceptibility of glioma in different ethnicities.
| S-EPMC3559473 | biostudies-literature
Project description:DNA repair enzymes play a pivotal role in platinum-based chemotherapy. Within the gene encoding for the base excision repair enzyme XRCC1, several nonsynonymous polymorphisms have been identified. It has been shown that the Arg399Gln single-nucleotide polymorphism results in a polymorphic enzyme that is less capable of initiating DNA repair. We developed a multiplex pyrosequence assay to simultaneously detect two nonsynonymous polymorphisms within the XRCC1 gene. Both of these polymorphisms resulted in amino acid changes: G/A in codon 399 changes Arg into Gln, and deletion of A in the second position of codon 576 results in a stopcodon. We established the frequency of these mutations in 270 patients suffering from colorectal cancer. Allele frequencies of G in second position of codon 399 and A in the second position codon 576 are 61.1 and 99.6%, respectively, in these patients. This fast and reliable method allows for simultaneous detection of the infrequent mutant C or CT alleles instead of the A deletion at codon 576. The method may be used in pharmacogenetic studies of platinum-based chemotherapy.
| S-EPMC1867628 | biostudies-literature