• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5957-5960
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• 2013

Background: Gliomas are the most common type of primary brain tumor in adults, and the X-ray repair complementing group 1 gene (XRCC1) is an important candidate gene influencing its risk. The objective of this study was to detect the influence of XRCC1 genetic polymorphisms on glioma risk. Materials and Methods: A total of 629 glioma patients and 641 cancer-free subjects were enrolled in this case-control study. The genotypes of the c.1471G>A genetic polymorphism were determined by created restriction site-polymerase chain reaction (CRS-PCR) and DNA sequencing methods. The influence of the XRCC1 genetic polymorphism on glioma risk was evaluated by association analysis. Results: Our data indicated that the alleles/genotype of this genetic variant was statistically associated with glioma risk. The AA genotype was statistically associated with the increased risk of glioma compared to the GG wild genotype (odds ratios (OR) = 1.89, 95% CI 1.25-2.87, P = 0.003). The allele-A may contribute to increased the susceptibility to glioma (OR = 1.23, 95% CI 1.04-1.46, P = 0.017). Conclusions: These preliminary findings indicate that the c.1471G>A genetic polymorphism of XRCC1 has the potential to influence glioma susceptibility, and might be used as molecular marker for assessing glioma risk.

• 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.7
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• pp.3273-3278
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• 2014

Background: Various studies have evaluated the relationship between X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln polymorphism and hepatocellular carcinoma (HCC) risk, but the conclusions have been inconsistent and underpowered. The purpose of this updated meta-analysis was to examine whether XRCC1 Arg399Gln polymorphism confers susceptibility to HCC. Methods: Eligible studies extracted from PubMed, Embase, Cochrane Library, VIP (chinese) and CNKI (chinese) up to November 2013 were included in the study. Pooled odds ratio (OR) together with their 95% confidence interval (CI) were estimated to evaluate XRCC1 Arg399Gln polymorphism and HCC risk. Results: Finally, 21 studies with 4,170 cases and 5,030 controls were involved in our meta-analysis. The results demonstrated that there was significant association between Arg399Gln polymorphism and HCC risk under two contrast models in overall populations (AG vs GG: OR=1.265, 95%CI=1.036-1.545, p=0.021; AA+AG vs GG: OR=1.240, 95%CI=1.021-1.506, p=0.030). In subgroup analyses, significant association was found in Asians (A vs G: OR=1.175, 95%CI=1.013-1.362, p=0.033; AG vs GG: OR=1.317, 95%CI=1.070-1.622, p=0.009; AA+AG vs GG: OR=1.289, 95%CI=1.055-1.575, p=0.013) and Caucasians (A vs G: OR=0.591, 95%CI=0.361-0.966, p=0.036; AA+AG vs GG: OR=0.468, 95%CI=0.234-0.934, p=0.031). Conclusions: The results suggest that XRCC1 Arg399Gln polymorphism may increase HCC risk especially among Asians. However, XRCC1 Arg399Gln polymorphism might act as a protective role against HCC among Caucasians.

• 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.

• 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.14 no.11
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• pp.6703-6707
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• 2013

Background: Numerous epidemiological studies have been conducted to evaluate the association between variants of the DNA repair gene XRCC3 and cancer risk. Here we focused on one XRCC3 polymorphism and development of cervical cancer, performing a meta-analysis. Methods: The pooled association between the XRCC3 Thr241Met polymorphism and cervical cancer risk was assessed by odds ratios (ORs) and their 95% confidence intervals (95%CIs). Results: A total of 5 case-control studies met the inclusion criteria. The pooled ORs for the total included studies showed no association among homozygotes TT vs. CC: OR=1.93, 95%CI=0.68-5.49, P=0.22; dominant model TT+TC vs. CC: OR=1.37, 95%CI=0.90-2.06, P=0.14; and recessive model TT vs. TC+CC: OR=1.76, 95%CI=0.68-4.55, P=0.25, but might be a slight risk factor for cervical cancer in heterozygote contrast TT vs. CT: OR= 1.33, 95%CI=1.04-1.71, P=0.02. In subgroup analysis, significant associations were found for Asians under all genetic models. Conclusions: Our meta-analysis suggested the XRCC3 Thr241Met polymorphism might not act as a cervical cancer risk factor overall. However, in subgroup analysis, a significant association was found in Asians under all genetic models. The association should be studied with a larger, stratified population, especially for Asians.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3601-3604
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• 2012

Purpose: Numerous studies have evaluated the association between XRCC1 Arg399Gln gene polymorphism and hepatocellular carcinoma risk in the Chinese Han population. However, the results have been inconsistent. We therefore here examined whether the XRCC1 Arg399Gln gene polymorphism confers hepatocellular carcinoma risk by conducting a meta-analysis. Methods: PubMed, Google scholar and China National Knowledge Infrastructure databases were searched for eligible articles in English and Chinese that were published before April 2012. Results: 6 studies involving 1,246 patients with hepatocellular carcinoma and 1,953 controls were included. The association between XRCC1 Arg399Gln gene polymorphism and hepatocellular carcinoma in the Chinese Han population was significant under GG vs AA (OR = 1.48, 95% CI = 1.13 to 1.94). Limiting the analysis to the studies with controls in the Hardy-Weinberg equilibrium, the results were persistent and robust. Conclusions: In the Chinese Han population, the XRCC1 Arg399Gln gene polymorphism is associated with an increased hepatocellular carcinoma risk.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10457-10462
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• 2015

Homologous recombination repair (HRR) plays an important role in protection against carcinogenic factors. Genes regulating the HRR mechanisms may impair their functions and consequently result in increased cancer susceptibility. RAD 51 and XRCC3 are key regulators of the HRR pathway and genetic variability in these may contribute to the appearance and progression of various cancers including head and neck cancer (HNC). The aim of the present study was to compare the distribution of genotypes of RAD51 (135G/C, 172 G/T) and XRCC3 (Thr241Met) polymorphisms between HNC patients and controls. Each polymorphism was genotyped using the polymerase chain reaction-restriction fragment length polymerase (PCR-RFLP) technique in 200 pathologically confirmed HNC patients along with 150 blood samples from normal, disease free healthy individuals. We observed that homozygous variant CC genotype of RAD51 135G/C was associated with a 2.5 fold increased HNC risk (OR=2.5; 95%CI=0.69-9.53; p<0.02), while second polymorphism of RAD 51 172 G/T, heterozygous variant GT genotype was associated with a 1.68 fold (OR=1.68; 95%CI=1.08-2.61; p<0.02) elevation when compared with controls. In the case of the Thr241Met polymorphism of XRCC3, we observed a 16 fold (OR=16; 95% CI=3.78-69.67; p<0.0002) increased HNC risk in patients compared to controls. These results further suggested that RAD51 (135G/C, 172 G/T) and XRCC3 (Thr241Met) polymorphisms may be effective biomarkers for genetic susceptibility to HNC. Larger studies are needed to confirm our findings and identify the underlying mechanisms.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.5201-5205
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• 2012

Background: To evaluate the role of the X-ray repair cross complementing group 3 (XRCC3) T241M polymorphism in head and neck cancer susceptibility. Materials and Methods: We performed a meta-analysis of all available studies, which included 3,191 cases and 5,090 controls. Results: Overall, a significant risk effect of the T241M polymorphism was not found under homologous contrast (MM vs TT: OR=1.293, 95% CI=0.926-1.805; TM vs TT: OR=1.148 95% CI=0.930-1.418) and recessive models (MM vs TT+TM): OR=1.170, 95% CI=0.905-1.512, but a significantly increased risk was observed under a dominant model (MM+TM vs TT): OR=1.243, 95% CI=1.001-1.544. In stratified analyses, there were no significant associations for Asians or Caucasians. Conclusion: Our meta-analysis suggested the XRCC3 241M allele (MM+TM) might act as a head and neck cancer risk factor among all subjects, and the effect of T241M polymorphism on head and neck susceptibility should be studied with a larger, stratified population.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6423-6427
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• 2012

Background: Functional single nucleotide polymorphisms of x-ray repair cross-complementing protein 1 (XRCC1) have been suspected to contribute to uterine cervical cancer risk for a long time; however, most previous case-control studies were small sized and biased. Additionally, recent studies suggested that XRCC1 polymorphisms could be a biomarker of response to platinum-based chemotherapy. Methods: A comprehensive search was conducted to retrieve eligible studies and odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to measure association strength. Results: A total of 13 studies were identified and analyzed. We found that the Arg194Trp polymorphism (Trp vs. Arg, OR=1.342, 95% CI: 1.176) was associated with increased risk of cervical cancer, while no significant association was found with Arg280His (His vs. Arg, OR=1.059, 95% CI: 0.863, 1.299) or Arg399Gln (Gln vs. Arg, OR=1.144, 95% CI: 0.938, 1.394). As for response to platinum-based chemotherapy, the variant XRCC1 399Gln allele (Gln vs. Arg, OR=0.345, 95% CI: 0.163, 0.729) was linked with a poor response; however, the Arg194Trp polymorphism (TrpArg vs. ArgArg, OR=6.421, 95% CI: 1.573, 26.205) predicted a good response. Conclusion: The Arg194Trp polymorphism of XRCC1 increases risk of cervical cancer; the variant 399Gln allele predicts poor response to platinum-based chemotherapy, while the Arg194Trp polymorphism indicates a good response.