DNA repair gene XRCC1 and XPD polymorphisms and their association with coronary artery disease risks and micronucleus frequency (original) (raw)
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ERCC2/XPD, is one of the core genes involved in transcription-coupled NER pathway (a fundamental defense mechanism against the carcinogenic effects of sunlight and certain genetic defects in the DNA repair pathways); and its functional polymorphisms may be associated with the risk of different types of cancers. The present investigation includes Lys751Gln & Asp312Asn polymorphisms in a case-control hospital based study in 100 Kashmiri GC patients &100 age & sex matched controls. It was observed that most of the cases were males, numbering 72 with a maximum number falling in the age group of 56-65 years; whereas female GC cases were only 28 with a maximum number in the age group of 56-65 years as in the males. The male GC cases were all smokers especially hooka smokers. All female cases were non-smokers. Statistically significant results were observed in GC cases who were smokers with a pvalue of <0.0001; χ 2 =63.15; O.R. =7.427 and 3.919to 14.081 of 95%C.I., suggesting a strong correlation between smoking and the risk of GC. Among the dietary factors the intake of salt tea that was consumed by both the GC cases as well controls was found to be statistically insignificant (Fishers exact test =0.134; O.R. =1.644 and 95% C.I. = 0.90 to 2.976). Statistically significant values were found in GC cases who included preserved EUROPEAN ACADEMIC RESEARCH-Vol.II, Issue 11/February 2015 14147 dried foods in their diet. (Fishers exact test = <0.0001; O.R. = 11.643; and 95% C.I. =5.542 to 24.46). The intake of too much of spices and chillies in the diet of GC cases was also found to be statistically significant. (Fishers exact test =0.007; O.R. = 2.257 and 95% C.I. = 1.28 to 3.979) suggesting the role of these dietary foods in the GC risk. Family history of carcinogenesis although found in the small number of GC cases and none in the control group was moderately statistically significant. (Fishers exact test =0.029). The genotypic frequencies of ERCC2codon 751 showed a significant difference between cases and controls ((χ 2 =16.85 p≤0.0001)). Allelic frequencies revealed statistically significant excess of Gln allele in cases as compared to controls and a low percentage of Lys allele in cases as compared in controls (Fishers exact test = ≤0.0001, OR =0.213, 95% CI 0.106 to 0.426). The codon 312 of ERCC2 studied also showed statistically significant genotypic frequencies between cases and controls (χ 2 8.75 p value of 0.013). Allelic frequencies revealed statistically significant excess of Asn allele in cases as compared to controls and a low percentage of Asp allele in cases as compared in controls (Fishers exact test = 0.001, O.R = 0.384, 95% C.I = 0.218 to 0.675). The magnitude and statistical significance of Asp312Asn polymorphism was smaller and weaker than the Lys751Gln polymorphism studied in the present study of GC cases vs controls.
Asian Pacific Journal of Cancer Prevention Apjcp, 2010
Damage to DNA may lead to carcinogenesis but is repaired through activation of pathways involving polymorphic enzymes, including human 8-oxoguanine glycosylase 1 (OGG1). The present study aimed to assess the role of genetic variants of DNA repair gene OGG1 Ser326Cys in susceptibility to gastric cancer in Kashmir valley. A case control study was performed in 303 subjects (108 gastric cancer and 195 healthy controls), all genotyped through the polymerase chain reaction (PCR). Data weres statistically analyzed using the chi-square test and the logistic regression model. The distribution of OGG1 genotypes among controls and gastric cancer cases did not show any significant differences. Although smokers and high salted tea drinkers themselves were at higher risk for gastric cancer (OR=8.975, P=0.0001; OR=14.778, P=0.0001), interaction with OGG1 Ser326Cys did not further modulate the risk. In conclusion, our findings suggest that the OGG1 polymorphism does not influence either gastric cancer risk independently or by interaction with smoking or salted-tea consumption in the Kashmir valley.
Genetic polymorphisms of XRCC1 and risk of gastric cancer
Cancer Letters, 2002
Coding polymorphisms of the DNA repair gene XRCC1 have been shown to affect the DNA repair capacity and to be associated with genetic susceptibility to carcinogenesis. In our association study between three amino acid substitution polymorphisms of XRCC1 (Arg194Trp, Arg280His, and Arg399Gln) and the risk of gastric cancer in the Korean population, none of the polymorphisms were associated with increased risk of gastric cancer. We then extended our study by building haplotypes of the entire XRCC1 gene with six single neuclotide polymorphisms (SNPs), including two novel polymorphisms at the 5 0flanking sequence. When haplotype frequencies in cases and controls and haplotype-specific odds ratios (ORs) were estimated, haplotype A (194Trp, 280Arg, and 399Arg) was associated with significant reduction in gastric cancer risk (adjusted OR ¼ 0.65, 95% CI ¼ 0.43-0.99) whereas haplotype D (194Arg, 280Arg, and 399Arg alleles) was a risk type for gastric cancer (adjusted OR ¼ 1.57, 95% CI ¼ 0.93-2.65). The association with the haplotype D was more pronounced in the cancers of antrum (adjusted OR ¼ 2.06, 95% CI ¼ 1.03-2.00). Our results suggest that the haplotype estimation is advantageous for association studies of such a complex disease as gastric cancer.
Polymorphisms in DNA repair genes XRCC2 and XRCC3 risk of gastric cancer in Turkey
We studied the prevalence of polymorphisms in genes XRCC2 and XRCC3 in stomach cancer patients who lived in North Eastern Turkey. A total of 61 cancer patients and 78 controls were included in this study. Single nucleotide changes were studied in XRCC2 and XRCC3 genes at locus Arg188His and Th r241Met. Blood samples were taken from the patients and controls, and DNA was isolated. Th e regions of interest were amplifi ed using a polymerase chain reaction method. After amplifi cation, we used restriction enzymes (HphI and NcoI) to digest the amplifi ed product. Digested product was then run through gel electrophoresis. We identifi ed changes in the nucleotides in these specifi c regions. It was found that the Arg188His polymorphism of the XRCC2 gene was about 39 (24 out of the 61) among cancer patients. However, only 15 (12 out of 78) of the control group indicated this polymorphism. We also observed that 18 of the 61 cancer patients (29) carried the Th r241Met polymorphism of the XRCC3 gene whereas 11 of the 78 (14) individuals in the control group had the polymorphism. Our results showed a signifi cant diff erence in polymorphism ratios between the cancer patients and health control group for the regions of interest. Th is result clearly showed that these polymorphisms increase the risk of stomach cancer and might be a strong marker for early diagnosis of gastric cancer.
Journal of Gastrointestinal Cancer, 2009
Background Kashmir Valley has elevated incidence rate of gastric cancer (GC) and several environmental, host genetic factors have been suspected for it. Xenobiotic carcinogen exposure and interindividual differences in its cellular metabolism may modulate susceptibility to GC. Aim of the Study The aim of this study is to investigate the role of genetic variants of xenobiotic-metabolizing genes with susceptibility to GC in Kashmir Valley. Methods A case–control study was performed in 303 subjects (108 GC and 195 healthy controls) to analyze the association of polymorphisms in GSTM1, GSTT1, GSTP1, GSTM3, CYP1A1, and CYP2E1 genes in susceptibility to GC in Kashmir Valley. All subjects were genotyped through polymerase chain reaction–restriction fragment length polymorphism. Results GSTM1null and CYP2E1c1c2 genotypes imparted risk for GC (odds ratio [OR] = 1.98, 95% confidence interval [95%CI] = 1.22–3.21, P = 0.006 and OR = 2.56, 95%CI = 1.25–5.25, P = 0.010, respectively). GSTM3AB genotype/B allele was found to be associated with low risk for GC. Smokers and high salted tea consumers themselves were at higher risk for GC (OR = 8.98, 95%CI = 5.16–15.62, P = 0.0001 and OR = 14.78, 95%CI = 8.02–27.23, P = 0.0001, respectively). Cancer risk was further enhanced in smokers with the GSTM1null genotype. Conclusion The results suggest that GSTM1null, GSTM3AB, and CYP2E1c1c2 genotypes modulate the risk of GC whereas GSTM1null genotypes enhance the risk of GC for smokers in the Kashmir population.
Research in Molecular Medicine, 2020
Background: Gastric cancer is one of the most common malignancies in the world. It may result from a defect in the genes involved in DNA repair. One of the essential genes in the repair pathway is the XRCC1 gene that its polymorphisms in the human population play a role in gastric cancer susceptibility. The main purpose of this study was to investigate the association of 194C/T and 399G/A polymorphisms of the XRCC1 gene with gastric cancer in an Iranian population. Materials and Methods: A total of 66 patients with gastric cancer and 67 control individuals were enrolled in our study. Following DNA extraction from blood samples, polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Results: The allele frequencies of C/T of XRCC1-194C/T in the control and patients groups were 83.17% and 71.29%, respectively. Moreover, The allele frequencies of G/A of XRCC1-399G/A in control and patient groups were 66.34% and 62.38%, respectively. Our results indicated a significant positive association between the distribution T/C alleles and the risk of gastric cancer (χ 2 : 5.37 and P=0.02), but no significant association was found in the distribution G/A alleles (χ 2 : 0.47 and P=0.48). Conclusion: Altogether, these findings indicate a positive association between the distribution of 194T/C alleles of XRCC1 and the risk of gastric cancer and the presence of the C allele may increase the risk of gastric cancer.
Selected DNA repair polymorphisms and gastric cancer in Poland
Carcinogenesis, 2005
Impaired DNA repair capacity may adversely affect cancer risk, particularly in subjects exposed to DNA damaging carcinogens, as found in tobacco smoke, or among subjects deficient for protective factors, as found in fruits and vegetables. We studied tobacco use, fruit and vegetable intake, and common non-synonymous single nucleotide polymorphisms in four DNA repair genes in relation to gastric cancer risk, in a population-based, case-control study of 281 incident gastric cancer cases and 390 controls, in Warsaw, Poland. Multivariate logistic regression analysis was performed to calculate odds ratios (OR) and 95% confidence intervals (CI). Increased risks of gastric cancer were found for smokers (OR ¼ 3.1, CI ¼ 1.9-5.1 for packyears !40 versus never smokers) and subjects with low fruit intake (OR ¼ 2.2, CI ¼ 1.3-3.6 for 1st versus 4th quartile); risk associated with vegetable intake was not statistically significant. Allele frequencies among the controls were consistent with those previously reported for the 5 polymorphisms studied: XRCC1-Arg399Gln, XPD-Lys751Gln, MGMT-Ile143Val, Leu84Phe, and XRCC3-Thr241Met. None of the studied polymorphisms were independently associated with gastric cancer risk. Smoking-associated risks, however, were greatest for carriers of the XRCC1-399 ArgArg genotype (P interaction ¼ 0.004). Risks associated with low intake of fruits or vegetables tended to be modified by selected polymorphisms in XRCC1, XPD and MGMT (P interaction ¼ 0.1-0.2). Risk modification was not found for the other repair polymorphisms. Selected DNA repair polymorphisms did not have independent effects on gastric cancer risk; however, they may modify smoking-and probably diet-related risks for this disease. These results need replication in larger epidemiological studies of gastric cancer.
BMC cancer, 2017
Previous studies have found that polymorphisms of the DNA repair gene X-ray repair cross-complementing group 1(XRCC1) and environmental factors are both associated with an increased risk of stomach cancer, but no study has reported on the potential additive effect of these factors among Thai people. The aim of this study was to investigate whether the risk of stomach cancer from XRCC1 gene polymorphisms was modified by environmental factors in the Thai population. Hospital-based matched case-control study data were collected from 101 new stomach cancer cases and 202 controls, which were recruited from2002 to 2006 and were matched for gender and age. Genotype analysis was performed using real-time PCR-HRM. The data were analysed by the chi-square test and conditional logistic regression. The Arg/Arg homozygote polymorphism of the XRCC1 gene was associated with an increased risk of stomach cancer in the Thai population (OR adj, 3.7; 95%CI, 1.30-10.72) compared with Gln/Gln homozygosit...
Asian Pacific journal of cancer prevention : APJCP, 2016
The XRCC1 protein facilitates various DNA repair pathways; single-nucleotide polymorphisms (SNPs) in this gene are associated with a risk of gastrointestinal cancer (GIC) with inconsistent results, but no data have been previously reported for the Sabah, North Borneo, population. We accordingly investigated the XRCC1 Arg194Trp and Arg399Gln SNPs in terms of GIC risk in Sabah. We performed genotyping for both SNPs for 250 GIC patients and 572 healthy volunteers using a polymerase chain reaction- restriction fragment length polymorphism approach. We validated heterozygosity and homozygosity for both SNPs using direct sequencing. The presence of a variant 194Trp allele in the Arg194Trp SNP was significantly associated with a higher risk of GIC, especially with gastric and colorectal cancers. We additionally found that the variant 399Gln allele in Arg399Gln SNP was associated with a greater risk of developing gastric cancer. Our combined analysis revealed that inheritance of variant all...
American Journal of Epidemiology, 2011
The authors performed a systematic review and meta-analysis of associations of the x-ray repair crosscomplementing 1 gene (XRCC1) single nucleotide polymorphisms (SNPs) Arg194Trp, Arg280His, and Arg399Gln with gastric cancer risk, based on eligible studies retrieved from electronic databases for the period January 2000-December 2009. Ultimately, 12, 6, and 3 studies were found to be eligible for meta-analyses of Arg399Gln, Arg194Trp, and Arg280His, respectively. Regrouping was adopted in accordance with the most probably appropriate genetic models. Potential sources of heterogeneity were sought out. For overall gastric cancer, the pooled odds ratios for Arg399Gln, Arg194Trp, and Arg280His were 1.04 (95% confidence interval (CI): 0.90, 1.20; P ¼ 0.572), 0.83 (95% CI: 0.68, 1.01; P ¼ 0.059), and 1.18 (95% CI: 0.92, 1.50; P ¼ 0.194), respectively. After stratification of the Arg399Gln SNP data by anatomic type (cardia vs. noncardia), the pooled odds ratio was 1.07 (95% CI: 0.84, 1.37; P ¼ 0.568). The authors conclude that the 3 SNPs evaluated are not associated with risk of gastric cancer. The Arg399Gln SNP is not associated with the cardia type of gastric cancer. Evidently, the heterogeneity regarding the Arg399Gln SNP across studies is not explained by ethnicity, genotyping technique, sample size, or date of publication.