• 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.14 no.9
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• pp.5483-5487
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• 2013

Background: Associations between Arg399Gln, Arg194Trp and Arg280His polymorphisms of the XRCC1 gene and risk of differentiated thyroid carcinoma (DTC) have been widely studied but the findings are contradictory. Methods: We performed a meta-analysis in the present study using STATA 11.0 software to clarify any associations. Electronic literature databases and reference lists of relevant articles revealed a total of 10, 6 and 6 published studies for the Arg399Gln, Arg194Trp and Arg280His polymorphisms, respectively. Results: No significant associations were observed between Arg399Gln and DTC risk in all genetic models within the overall and subgroup meta-analyses, while the Trp/Trp vs Arg/Arg and recessive model of the Arg194Trp polymorphism was associated with DTC susceptibility, and the dominant model of Arg280His polymorphism contributed to DTC susceptibility in Caucasians. Conclusions: Our meta-analysis suggests that XRCC1 Arg194Trp may be a risk factor for DTC development.

• 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.

• 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.13 no.12
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• pp.6385-6390
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• 2012

A number of studies have been conducted to explore the association of XRCC1 polymorphisms with thyroid cancer risk, but the results have been inconsistent. Thus we performed the present meta-analysis to clarify this issue based on all of the evidence available to date. Relevant studies were retrieved by searching PubMed and statistical analysis conducted using Stata software. Nine studies were included in this meta-analysis (1,620 cases and 3,557 controls). There were 6 studies (932 cases and 2,270 controls) of the Arg194Trp polymorphism, 7 studies (1432 cases and 3356 controls) of the Arg280His polymorphism and 9 studies (1,620 cases and 3,557 controls) for the Arg399Gln polymorphism. No association of XRCC1 Arg194Trp, Arg280His and Arg399Gln polymorphism with thyroid cancer risk was observed in the overall analysis. However, subgroup analysis revealed: 1) an elevated risk in aa vs AA analysis (OR=2.03, 95%CI= 1.24-3.31) and recessive genetic model analysis (OR=1.93, 95%CI= 1.20-3.08) in the larger sample size trials for XRCC1 Arg194Trp polymorphism; 2) a decreased thyroid cancer risk on subgroup analysis based on ethnicity in Aa vs AA analysis (OR=0.84, 95%CI= 0.72-0.98) and in a dominant genetic model (OR=0.84, 95%CI= 0.72-0.97) in Caucasian populations for the XRCC1 Arg399Gln polymorphism; 3) a decreased thyroid cancer risk on subgroup analysis based on design type in Aa vs AA analysis (OR=0.72, 95% CI= 0.54-0.97) among the PCC trials for the Arg399Gln polymorphism. Our results suggest that the XRCC1 Arg399Gln polymorphism may be associated with decreased thyroid cancer risk among Caucasians and XRCC1 Arg194Trp may be associated with a tendency for increased thyroid cancer risk in the two larger sample size trials.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1925-1931
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• 2016

Background: 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. Materials and Methods: 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. Results: 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 alleles in both SNPs increased the GIC risk in Sabah population. Based on our etiological analysis, we found that subjects ${\geq}50years$ and males who carrying the variant 194Trp allele, and Bajau subjects carrying the 399Gln allele had a significantly increased risk of GIC. Conclusions: Our findings suggest that inheritance of variant alleles in XRCC1 Arg194Trp and Arg399Gln SNPs may act as biomarkers for the early detection of GIC, especially for gastric and colorectal cancers in the Sabah population.

• 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.

• 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.13 no.10
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• pp.5007-5010
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• 2012

Objective: We conducted a prospective study to test the association between three amino acid substitution polymorphismic variants of DNA repair genes, XRCC1 (Arg194Trp), XRCC1(Arg280His) and XRCC1 (Arg399Gln), and clinical outcome of ovarian cancer patients undergoing adjuvant chemotherapy. Methods: 195 patients with primary advanced ovarian cancer and treated by adjuvant chemotherapy were included in our study. All were followed-up from Jan. 2007 to Jan. 2012. Genotyping of XRCC1 polymorphisms was conducted by TaqMan Gene Expression assays. Results: The XRCC1 194 Trp/Trp genotype conferred a significant risk of death from ovarian cancer when compared with Arg/Arg (HR=1.56, 95%CI=1.04-3.15). Similarly, those carrying the XRCC1 399 Gln/Gln genotype had a increased risk of death as compared to the XRCC1 399Arg/Arg genotype with an HR (95% CI) of 1.98 (1.09-3.93). Conclusion: This study is the first to provide evidence that XRCC1 gene polymorphisms would well be useful as surrogate markers of clinical outcome in ovarian cancer cases undergoing adjuvant chemotherapy.

• 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.