• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3809-3813
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• 2013

Background: 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. Materials and Methods: 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 and Conclusions: 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 significant association. In conclusion the XRCC1rs1799782 polymorphism may be involved in the etiology of breast cancer in the Saudi population. Confirmation of our findings in larger populations of different ethnicities is warranted.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6779-6782
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• 2013

Background: The DNA repair gene XRCC1 Arg399Gln gene polymorphism has been found to be implicated in the development of various cancers, including colorectal cancer (CRC), in different populations. We aimed to determine any association of this polymorphism with the risk of CRC in Kashmir. Materials and Methods: A total of 120 confirmed cases of CRC and 146 healthy cancer free controls from the Kashmiri population were included in this study. Genotyping was carried out by the polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) method. Results: Genotype frequencies of XRCC1 Arg399Gln observed in controls were 34.2%, 42.5% and 23.3% for GG (Arg/Arg), GA (Arg/Gln), AA( Gln/Gln), respectively, and 28.3%, 66.7% and 5% in cases, with an odds ratio (OR)=5.7 and 95% confidence interval (CI) =2.3-14.1 (p=0.0001). No significant association of Arg399Gln SNP with any clinicopathological parameters of CRC was found. Conclusions: We found the protective role of 399Gln allele against risk to the development of CRC. The XRCC1 heterozygote status appears to be a strong risk factor for CRC development in the Kashmiri population.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.355-358
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• 2013

XRCC1 genetic polymorphisms could be associated with increased risk of various cancer, including hepatocellular carcinoma (HCC), the fifth most common cancer. We here conducted a study to explore the role of selective SNPs of the XRCC1 and XPD genes in the prognosis of HCC. A total of 231 cases were collected, and genotyping of XRCC1 Arg194Trp, XRCC1 Arg399Gln, XPD Lys751Gln and XPD Asp312Asn was performed by duplex polymerase-chain-reaction with the confronting-two-pair primer method. Our findings indicated XRCC1 399Gln/Gln genotype was associated with a significant difference in the median survival time compared with patients carrying Arg/Trp and Arg/Arg genotypes, and individuals with XPD 751 Gln/ Gln genotype had a significantly greater survival time than patients carrying Lys/Lys and Lys/Gln genotypes. The Cox's regression analysis showed individuals carrying XRCC1 399Trp/Trp genotype had 0.55 fold risk of death from HCC than Arg/Arg genotype. Similarly, XPD 751Gln/Gln had a strong decreasein comparison to XPD Lys/Lys carriers with an HR of 0.34. These results suggest that polymorphisms in XRCC1 and XPD may have functional significance in the prognosis of HCC.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.449-452
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• 2013

Polymorphisms in DNA repair genes have been shown to influence DNA repair processes and to modify cancer susceptibility. Here we conducted a case-control study to assess the role of potential SNPs of DNA repair genes on the risk of glioma and meningioma. We included 297 cases and 458 cancer-free controls. Genotyping of XRCC1 Gln399Arg, XRCC1 Arg194Trp, XRCC2 Arg188His, XRCC3 Thr241Met, XRCC4 Ala247Ser, ERCC1 Asn118Asp, ERCC2 Lys751Gln and ERCC5 Asp1558His were performed in a 384-well plate format on the Sequenom MassARRAY platform. XRCC1 Arg194Trp (rs1799782) and ERCC2 Asp312Asn rs1799793 did not follow the HWE in control group, and genotype distributions of XRCC1 Gln399Arg rs25487, XRCC2 Arg188His rs3218536 and ERCC2 Asp312Asn rs1799793 were significantly different between cases and controls (P<0.05). We found XRCC1 399G/G, XRCC1 194 T/T and XRCC3 241T/T were associated with a higher risk when compared with the wild-type genotype. For ERCC5 Asp1558His, we found G/G genotype was associated with elevated susceptibility. In conclusion, our study has shown that XRCC1 Gln399Arg, XRCC1 Arg194Trp, XRCC3 Thr241Met and ERCC5 Asp1558His are associated with risk of gliomas and meningiomas. This finding could be useful in identifying the susceptibility genes for these cancers.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10329-10334
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• 2015

Background: To systematically summarize the association between the X-ray repair cross complementing 3 (XRCC3) gene polymorphism and oral cancer susceptibility by meta-analysis. Materials and Methods: Databases including PubMed, EMbase, CNKI, VIP and WanFang Data were searched to identify case-control studies concerning the association between an XRCC3 gene polymorphism and the risk of oral cancer from the inception to June 2014. Two reviewers independently screened the literature according to the criteria, extracted the data and assessed the quality. Then meta-analysis was performed using Stata 11.0 software. Results: Seven published case-control studies including 775 patients with oral cancer and 1922 controls were selected. Associations between the rs861539 polymorphism and overall oral cancer risk were not statistically significant in all kinds of comparison models (CT vs CC: OR=0.94, 95%CI=0.74-1.18; TT vs CC: OR=0.94, 95%CI=0.64-1.38; dominant model: OR=0.95, 95%CI=0.76-1.18; recessive model: OR=0.94, 95%CI=0.69-1.29; allele T vs C: OR=0.97, 95%CI=0.84-1.11). In the stratified analysis by ethnicity, no significant associations were found among Asians and Caucasians. On stratification by tumor type, no significant associations were found for cancer and oral premalignant lesions. Conclusions: The XRCC3 gene polymorphism was not found to be associated with the risk of oral cancer. Considering the limited quality of the included case-control studies, more high quality studies with large sample size are needed to verify the above conclusion.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.189-193
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• 2013

Many epidemiological studies in Asian populations have investigated associations between the Arg399Gln gene polymorphism of X-ray repair cross complementing gene 1 (XRCC1) and risk of cervical carcinoma, but no conclusions have been available because of controversial results. Therefore a meta-analysis was conducted for clarification. Relevant studies were identified by searching the Pubmed, Embase, the Web of Science, Cochrane Collaboration's database, Chinese National Knowledge Infrastructure (CNKI), Wanfang database and China Biological Medicinse (CBM) until September, 2012. A total of eight studies were included in the present meta-analysis, which described 1,759 cervical carcinoma cases and 2,497 controls. Odds ratios (ORs) and corresponding 95% confidence intervals (95%CIs) as effect size were calculated by fixed-effect or random-effect models. The overall results indicated that the XRCC1-399G/A polymorphism was marginally associated with cervical carcinoma in Asians: OR (95%CI): 1.16 (1.07, 1.26) in the G/A vs G/G inheritance model, 1.24 (0.87, 1.76)in A/A vs G/G inheritance model, 1.13 (1.01, 1.27) in the dominant inheritance model and 1.18 (0.94, 1.47) in the recessive inheritance model. Subgroup analyses on sample size showed no significant correlation in the small-sample size group but the large-sample size group was consistent with the outcomes of overall meta-analysis. In the subgroup analysis by regions, we only found significant association under the G/A vs G/G inheritance model in the Chinese population. For the non-Chinese populations, no correlation was detected in any genetic inheritance model. In the Asian populations, XRCC1-399G/A gene polymorphism was implied to be associated with cervical carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.2055-2060
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• 2016

Background: Colorectal cancer (CRC) is one of the most common causes of death worldwide and in Thailand. The X-ray repair cross-complementary protein 1 (XRCC1) is required for efficient DNA repair. The effects of this gene on survival in colorectal cancer remain controversial and have not been reported in Thailand. The aim of this study was to investigate the association of the XRCC1 gene with survival of colorectal cancer patients in a Thai population. Materials and Methods: Data and blood samples were collected from 255 newly diagnosed and pathologically confirmed CRC patients who were recruited during the period 2002 to 2006 and whose vital status was followed up until 31 October, 2014. Real-time PCR-HRM was used for genotype identification. The Kaplan-Meier method, the log-rank test, and Cox proportional hazard regression were used to estimate cumulative survival curves and compare various survival distributions and adjusted hazard ratios. Results: Most of the cases were males, and the median age was 55 years. The median survival time was 2.43 years. The cumulative 1-, 3-, 5-, 7-, and 10 year survival rates were 76.70%, 39.25%, 26.50%, 16.60% and 3.56%, respectively. After adjustment, female gender, ages 50-59 and ${\geq}60years$, tumour stage III+IV, a signet-ring cell carcinoma, and poor differentiation had significant associations with increased risk of CRC death. While the XRCC1 Arg/Arg homozygote appeared to be a risk factor for CRC death, the association was not significant. Conclusions: The genetic variant in the XRCC1 may not be associated with the survival of CRC patients in Thailand. Further studies are needed to verify our findings.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.11
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• pp.4443-4448
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• 2014

Background: A number of studies have reported the association of X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln polymorphism with susceptibility to hepatocellular carcinoma (HCC). However, the results were inconsistent and inconclusive. The aim of this study was to comprehensively explore the association of XRCC1 Arg399Gln variant with HCC risk. Materials and Methods: Systematic searches of PubMed, Elsevier, Science Direct, CNKI and Chinese Biomedical Literature Database were performed. Pooled odds ratio (OR) with 95% confidence intervals (CI) was calculated to estimate the strength of association. Results: Overall, we observed an increased HCC risk among subjects carrying XRCC1 codon 399 Gln/Gln, Arg/Gln and Gln/Gln+Arg/Gln genotypes (OR=1.20, 95%CI: 1.05-1.38, OR=1.16, 95%CI: 1.05-1.28, and OR=1.14, 95%CI: 1.04-1.24, respectively) based on 20 studies including 3374 cases and 4633 controls. In subgroup analysis, we observed an increased risk of XRCC1 codon 399 Gln/Gln, Arg/Gln and Gln/Gln+Arg/Gln polymorphisms for HCC in hospital-based study (OR=1.25, 95%CI: 1.03-1.51, OR=1.21, 95%CI: 1.07-1.36 and OR=1.18, 95%CI: 1.06-1.31, respectively) and in Asian population (OR=1.19, 95%CI: 1.03-1.38, OR=1.17, 95%CI: 1.04-1.30 and OR=1.14, 95%CI: 1.04-1.25, respectively). Limiting the analysis to the studies with controls in agreement with Hardy-Weinberg equilibrium (HWE), we observed an increased HCC risk among Gln/Gln, Arg/Gln and Gln/ Gln+Arg/Gln genotype carriers (OR=1.17, 95%CI: 1.05-1.29, OR=1.12, 95%CI: 1.00-1.25 and OR=1.11, 95%CI: 1.02-1.21, respectively). Conclusions: This updated meta-analysis results suggest that XRCC1 Arg399Gln variants may contribute to HCC risk. Well-designed studies with larger sample size were required to further verify our findings.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4783-4788
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• 2012

Objective: Previous studies of the association between X-ray cross-complementing group 1 (XRCC1) gene polymorphisms and the gliomas risk have yielded conflicting results, and thus a meta-analysis was performed to provide a more accurate estimation. Methods: A computerized literature search of 5 electronic databases was conducted to identify the relevant studies. Fixed or random effect models were selected based on the heterogeneity test. Publication bias was estimated using Begg's funnel plots and Egger's regression test. Results: A total of 11 studies (3,810 cases and 6,079 controls), 7 studies (2,928 cases and 5,048 controls), and 4 studies (1,461 cases and 2,593 controls) were finally included in the analyses of the association between XRCC1 Arg399Gln, Arg194Trp, and Arg280His polymorphisms and glioma risk, respectively. The pooled results showed that GlnGln carriage was associated with moderately increased risk of gliomas in Asians (GlnGln vs. ArgArg, OR=1.490, 95%CI 1.031-2.153; GlnGln/ArgGln vs. ArgArg, OR=1.321, 95%CI 1.037-1.684), whereas a marginal association was revealed in Caucasians. For the Arg194Trp polymorphism, although a significant association was shown in the homozygous genotype comparisons (TrpTrp vs. ArgArg, OR = 2.209, 95%CI 1.398-2.945), no significant link was found on subgroup analysis stratified by ethnicity. With regard to the Arg280His polymorphism, no significant association was found in each comparison. No particular study was found to significantly influence the pooled results, and no potential publication bias was detected. Conclusions: This meta-analysis suggested that the XRCC1 Arg399Gln polymorphism is moderately associated with increased risk of gliomas in Asians, while Arg194Trp and Arg280His polymorphisms demonstrated no significant influence. Due to the limited studies and the potential confounders, further studies are needed to confirm these results.

• Archives of Plastic Surgery
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• v.33 no.4
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• pp.433-439
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• 2006

Purpose: DNA in most cell is regularly damaged by endogenous and exogenous mutagens. Unrepaired damage resulted in apoptosis or may lead to unregulated cell growth and cancer. Inheritance of genetic variants at one or more loci results in an reduced DNA repair capacity. These polymorphisms are highly prevalent in the population, and therefore the attributable risks for cancer could be high. Several studies have documented that polymorphisms of XRCC1, XPD and XRCC3 are associated with skin cancer, especially, XRCC1 among of them has been reported frequently. So, this study involves the relationship between mutation of XRCC1 of squamous cell and basal cell cancer of the skin and risk of cancer development in Korean population. Methods: In case control study, study population (n=100, each cancer) is patients who were pathologically diagnosed as skin cancer(squamous cell carcinoma and basal cell carcinoma) in Yonsei Wonju Christian Hospital and Bundang CHA General Hospital between 1998 and 2004. The samples of DNA from whom no history of premalignant skin lesion and other malignant diseases were reported belonged to the control group(n=210). Blood and tissue samples were analyzed for presence of XRCC1 Arg399Glu, Arg280His, Arg194Trp using PCR/ RFLP method. Results: For Korean, there was a significant correlation between XRCC1 Arg399Gln gene mutation and risk of basal cell carcinoma development(Arg 399Gln(GA), p=0.012, OR=2.016, 95% CI; 1.230-3.305) /Arg399Gln (AA), p=0.011, OR=1.864, 95% CI; 1.149-3.026)). And, there was also significant correlation between XRCC1 Arg194Trp and risk of skin squamous cell carcinoma development (Arg194Trp (CT+TT), p=0.041, OR=0.537, 95% CI; 0.301-0.960)). In contrast, there was no significant correlation between XRCC1 Arg280His and risk of either basal cell carcinoma or squamous cell carcinoma development. Conclusions: Our result present that XRCC1 Arg399 Gln in basal cell carcinoma and XRCC1 Arg194Trp in squamous cell carcinoma have possibility of cancer risk and biomarker in Korean population. But XRCC1 Arg280 His known having cancer risk on other studies is not associated with cancer risk to squamous cell carcinoma and basal cell carcinoma in Korean population.