• 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.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.1993-1999
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• 2014

Background: This study aimed to explore the role of XRCC1 (Arg399Gln) and XPD (Lys751Gln) gene polymorphisms, lifestyle and environmental factors as well as their possible interactions in propensity to develop lung cancer in a population with high incidence from North East India. Materials and Methods: A total of 272 lung cancer cases and 544 controls were collected and XRCC1 (Arg399Gln) and XPD (Lys751Gln) genotypes were analyzed using a polymerase chain reaction based restriction fragment length polymorphism assay. Conditional multiple logistic regression analysis was used to calculate adjusted odds ratios and 95% confidence intervals after adjusting for confounding factors. Results: The combined Gln/Gln genotype of XRCC1 and XPD genes (OR=2.78, CI=1.05-7.38; p=0.040) was significantly associated with increased risk for lung cancer. Interaction of XRCC1Gln/Gln genotype with exposure of wood combustion (OR=2.56, CI=1.16-5.66; p=0.020), exposure of cooking oil fumes (OR=3.45, CI=1.39-8.58; p=0.008) and tobacco smoking (OR=2.54, CI=1.21-5.32; p=0.014) and interaction of XPD with betel quid chewing (OR=2.31, CI=1.23-4.32; p=0.009) and tobacco smoking (OR=2.13, CI=1.12-4.05; p=0.022) were found to be significantly associated with increased risk for lung cancer. Conclusions: Gln/Gln alleles of both XRCC1 and XPD genes appear to amplify the effects of household exposure, smoking and betel quid chewing on lung cancer risk in the study population.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5721-5724
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• 2012

We conducted this study to detect associations between XRCC1 Arg399Gln and XPD Lys751Gln genotypes and survival of colorectal cancer patients treated with 5-FU/oxalipatin chemotherapy. We included 289 Chinese patients with advanced colorectal cancer, who had received 5-FU/oxalipatin chemotherapy as first-line treatment from January 2005 to January 2007. All patients were followed up till Nov. 2011. Genotyping for XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms was based upon duplex polymerase-chain-reaction with the PCR-RFLP method. In our study, we found the XRCC1 399 Gln/Gln genotype to confer significantly higher rates of response to chemotherapy when compared to the Arg/Arg genotype [OR (95% CI)= 2.56(1.57-2.55)]. patients with the XPD 751 Gln/Gln genotype had significantly higher rates of response to chemotherapy [OR (95% CI)= 1.54(0.87-2.65)] and those with the XRCC1 399 Gln/Gln genotype had a longer average survival time and significantly lower risk of death than did those with the Arg/Arg genotype [HR (95% CI)= 0.66(0.36-0.95)]. Similarly, those carrying the XPD 751Gln/Gln genotype had 0.51-fold the risk of death of those with XPD 751Lys/Lys [HR (95% CI)= 0.51(0.33 -0.94)]. In conclusion, it is suggested that the XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms should be routinely assessed to determine colorectal patients who are more likely to benefit from 5-FU/oxalipatin chemotherapy.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9621-9625
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• 2014

XRCC (X-ray cross-complementing group) genes contribute to important DNA repair mechanisms that play roles in the repair of single strand breaks (SSBs) induced by a variety of external and internal factors, including ionizing radiation, alkylating agents and reactive oxygen species. These repair genes have a pivotal role in maintaining genomic stability through different pathways of base excision repair (BER). The aim of this study was to investigate the XRCC3 Thr241Met gene polymorphism in colorectal cancer (CRC) in Kashmir. We investigated the genotype distribution of XRCC3 gene in 120 CRC cases in comparison with 150 healthy subjects and found a significant association between XRCC3 genotypes and CRC ($p{\leq}0.05$). Both heterozygous genotype (Thr/Met) as well as homozygous variant genotype (Met/Met) were moderately associated with elevated risk of CRC [OR=2.53; OR=2.29 respectively]. Also, Thr/Met and Met/Met genotypes demonstrated a significant association with the risk of CRC (p = 0.003). This study displayed a significantly elevated risk for CRC in individuals with XRCC3 Thr/Met and Met/Met Genotype of about 2.5 times that with the Thr/Thr wild genotype.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7479-7486
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• 2014

Background: Colorectal cancer (CRC) is one of the most common cancers worldwide. This study aimed to investigate the interaction between the presence of a polymorphism of the XRCC1 gene and known risk factors for colorectal cancer in Thailand. Materials and Methods: A hospital-based case-control study was conducted in Thailand. The participants were 230 histologically confirmed new cases and 230 controls matched by sex and age and recruited from the same hospital. Information about demographic characteristics, life style, and dietary habits was collected using structured interviews, and blood samples were taken which were used for the detection of a homozygous and heterozygous polymorphisms of XRCC1. Associations were assessed using multiple conditional logistic regression. Results: In the univariate analysis, factors found to be significantly associated with an increased risk for CRC were the presence of the XRCC1 AA homozygote (OR= 4.95; 95% CI: 1.99-12.3), a first degree family history of cancer (OR= 1.74; 95% CI: 1.18-2.58), and a high frequency of pork consumption (OR= 1.49; 95% CI: 1.00-2.21). Intakes of fish fruit and vegetables appeared to be protective factors, but the associations were not statistically significant. In the multivariate analysis only the XRCC1 AA homozygote polymorphism and a family history of cancer emerged as risk factors (OR= 4.96; 95% CI: 1.90- 12.95 and OR=1.80; 95% CI: 1.18-2.72, respectively). Conclusions: While the XRCC1 AA homozygote and a family history of cancer were found to be associated with an increased risk of CRC, none of the dietary intake variables were clearly identified as risk or protective factors. There is a need for further research to determine the reasons for this.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7419-7424
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• 2014

Gliomas are the most common type of primary brain tumors. The XRCC1 Arg194Trp variant affects the proliferating cell nuclear antigen(PCNA) binding region, which suggests that this mutation may contribute to gliomagenesis and a number of articles have examine the association between XRCC1 Arg194Trp and the susceptibility to glioma. However, the results were conflicting. Test of heterogeneity, sensitivity analysis, meta-analysis, and assessment of publication bias were all performed in our present meta-analysis, covering a total of 5,407 patients and 7,715 healthy persons. In the overall analysis the XRCC1 Arg194Trp polymorphism showed a significant association with glioma susceptibility in a recessive mode l(for TrpTrp vs ArgArg+ArgTrp: OR=1.918, 95%CI=1.575-2.336, $I^2$=2.3%). In addition, analysis of subgroups presented an increased risk in Asians and populations-based on hospitals. The results suggested that the XRCC1 Arg194Trp polymorphism is a genetic risk factor for glioma, especially in Asian population. To further evaluate gene-gene and gene-environment interactions on XRCC1 polymorphisms and glioma risk, thousands of subjects and tissue-specific biochemical characterizations are required.

• Radiation Oncology Journal
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• v.24 no.1
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• pp.30-36
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• 2006

Purpose: It is well known from clinical experience that acute complications of chemoradiation therapy vary from patients to patients. However, there are no known factors to predict these acute complications before treatment starts. The human XRCC1 gene is known as a DNA base excision repair gene. We investigated the possibilities of XRCC1 gene polymorphisms as a predictor for the acute complications of chemoradiation therapy in colorectal cancer patients. Materials and Methods: From July 1997 to June 2003, 86 colorectal cancer patients (71 rectal cancer, 13 sigmoid colon cancer and 2 colon cancer patients) were treated with chemoradiation therapy at the Department of Radiation Oncology, Inha University Hospital. Twenty-two patients were in stage B, 50 were in stage C, 8 were in stage D and 6 patients were unresectable cases. External radiation therapy was delivered with 10MV X-ray at a 1.8 Gy fraction per day for a total dose of radiation of $30.6{\sim}59.4 Gy$ (median: 54 Gy). All the patients received 5-FU based chemotherapy regimen. We analyzed the acute complications of upper and lower gastrointestinal tract based on the RTOG complication scale. The initial and lowest WBC and platelet count were recorded during both the RT period and the whole treatment period. Allelic variants of the XRCC1 gene at codons 194, 280 and 399 were analyzed in the lymphocyte DNA by performing PCR-RFLP. Statistical analyses were carried out with the SAS (version 6.12) statistical package. Results: When all the variables were assessed on the multivariate analysis, recurrent disease revealed the factors that significantly correlated with upper gastrointestinal acute complications. Arg399Gln polymorph isms of the XRCC1 gene, the radiation dose and the frequencies of chemotherapy during radiation therapy were significantly correlated with lower gastrointestinal complications. Arg399Gln polymorph isms also affected the decrease of the WBC and platelet count during radiation therapy. Conclusion: Although the present sample size was too small for fully evaluating this hypothesis, this study suggests that Arg399Gln polymorph isms of the XRCC1 genes may be used as one of the predictors for acute complications of chemoradiation therapy in colorectal cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2263-2268
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• 2015

Background: Many studies have reported associations of the X-ray repair cross-complementing group 3 (XRCC3) Thr241Met polymorphism with colorectal cancer (CRC) risk, but the results remained controversial. Hence, we performed the present meta-analysis with different inheritance models. Materials and Methods: We searched the PubMed and Google scholar databases for studies relating to associations between XRCC3 Thr241Met polymorphism and risk of CRC. 16 studies with 5,193 cases and 6,645 controls were finally included into the meta-analysis. Results: We found that the XRCC3 Thr241Met polymorphism was associated with increased CRC risk only under a dominant genetic model (CC+CT vs. TT: OR 0.575, 95%CI 0.498-1.665, p<0.001, $P_{heterogeneity}=0.00$, $I^2=83%$). There was a significant association between XRCC3 Thr241Met polymorphism and CRC risk in Caucasian in the overall 8 studies under only in the heterozygote genetic model (CT vs. TT: OR=0.929, 95%CI =0.806-1.070, P=0.308, $P_{heterogeneity}=0.002$, $I^2=57%$). Four studies evaluated the XRCC3 Thr241Met polymorphism and CRC risk in Asians. Two genetic models of the XRCC3 polymorphism were significantly correlated with increasing risk in Asians (dominant model: CC+CT vs. TT: OR= 0.609, 95%CI=411-0.902, P=0.013, $P_{heterogeneity}=0.54$, $I^2=0.00%$; Allele model: C vs. T: OR=0.708, 95 %=CI 0.605-0.829, p=0.000, $P_{heterogeneity}=0.000$, $I^2=92%$). The sensitivity analysis suggested stability of this meta-analysis and no publication bias was detected. Conclusions: In conclusion, this meta-analysis indicates that XRCC3 Thr241Met shows an increased CRC risk, particularly in Asians rather than Caucasians.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6385-6390
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• 2015

Background: 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. Materials and Methods: In this study we focused on the Arg194Trp polymorphism of the DNA repair gene XRCC1, involved in base excision repair (BER) and its role in colorectal cancer in Kashmiri population. A case-control study was conducted including 100 cases of colorectal cancer, and 100 hospital-based age- and sex-matched healthy controls to examine the role of XRCC1 genetic polymorphisms in the context of colorectal cancer risk for the Kashmiri population. Results: Genotype analysis of XRCC1 Arg194Trp was conducted with a restriction fragment length polymorphism (RFLP) method. The overall association between the XRCC1 polymorphism and the CRC cases was found to be significant (p < 0.05) with both the heterozygous genotype (Arg/Trp) as well as homozygous variant genotype (Trp/Trp) being moderately associated with the elevated risk for CRC [OR=2.01 (95% CI=1.03-3.94) and OR=5.2(95% CI=1.42-19.5)] respectively. Conclusions: Our results suggest an increased risk for CRC in individuals with XRCC1 Arg194Trp polymorphism suggesting BER repair pathway modulates the risk of developing colorectal cancer in the Kashmiri population.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.495-500
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• 2015

Background: Published studies have reported relationships between X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln polymorphism and lung cancer risk in Chinese population. However, the epidemiological results remained controversial. The objective of this study was to clarify the association of XRCC1 Arg399Gln polymorphism with lung cancer risk in the Chinese population. Materials and Methods: Systematic searches were performed through the database of Medline/Pubmed, Web of Science, Embase, CNKI and WanFang Medical Online. Odds ratios (ORs) with 95% confidence interval (95%CI) were calculated to estimate the strength of the association. Results: Overall, we observed an increased lung cancer risk among subjects carrying XRCC1 codon 399 Gln/Gln genotype (OR=1.36, 95%CI: 1.09-1.71) in the Chinese population on the basis of 19 studies with 5,416 cases and 5,782 controls. We did not observe any association between XRCC1 codon 399 Arg/Gln and Arg/Gln+Gln/Gln polymorphisms and lung cancer risk (OR=1.00, 95%CI: 0.92-1.08 and OR=1.05, 95%CI: 0.97-1.13, respectively). Limiting the analysis to studies with controls in agreement with Hardy-Weinberg equilibrium (HWE), we observed an increased lung cancer risk among subjects carrying XRCC1 codon 399 Gln/Gln genotype (OR=1.18, 95%CI: 1.01-1.38). When stratified by source of control, we observed an increased lung cancer risk among subjects carrying XRCC1 codon 399 Arg/Gln+Gln/Gln genotype on the basis of hospitalized patient-based controls (OR=1.21, 95%CI: 1.04-1.42) and among subjects carrying XRCC1 codon 399 Gln/Gln genotype on the basis of healthy subject-based controls (OR=1.22, 95%CI: 1.04-1.43). Conclusions: Our findings indicated that certain XRCC1 Arg399Gln variants might affect the susceptibility of lung cancer in Chinese population. Larger sample size studies are required to confirm our findings.