• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4413-4416
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• 2012

Aim: Individual differences in chemosensitivity and clinical outcome in non-small cell lung cancer (NSCLC) patients treatment with platinum-based chemotherapy may be due to genetic factors. Our study aimed to investigate the prognostic role of GSTP1, XRCC1 and XRCC3 in NSCLC patients treated with chemotherapy. Methods: A total of 460 cases were consecutively selected from The Affiliated Hospital of Nantong University between Jan. 2003 to Nov. 2006, and all were followed-up until Nov. 2011. Genotyping of GSTP1 Ile105Val, XRCC1 Arg194Trp, XRCC1 Arg399Gln and XRCC3 Thr241Met was conducted by duplex polymerase-chain-reaction with confronting-two-pair primer methods. Results: Patients with GSTP Val/Val exhibited a shorter survival time, and had a 1.89 fold greater risk of death than did those with the IIe/IIe genotype. For XRCC1 Arg194Trp, the variant genotype Trp/Trp was significantly associated with a decreased risk of death from NSCLC when compared with the Arg/Arg. Individuals carrying XRCC1 399Gln/Gln genotype had a longer survival time, with a lowered risk of death from NSCLC. Conclusion: This study indicated that GSTP1 Ile105Val, XRCC1 Arg194Trp and XRCC1Arg399Gln genes have a role in modifying the effect of platinum-based chemotherapy for NSCLC patients in a Chinese population. Our findings provide information for therapeutic decisions for individualized therapy in NSCLC cases.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.713-718
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• 2015

Background: A number of association studies have been carried out to investigate the relationship between genetic polymorphisms in DNA repair genes and response to radiotherapy-based multimodality treatment of patients with rectal cancer. However, their conclusions were inconsistent. The objective of the present study was to assess the role of DNA repair gene genetic polymorphisms in predicting genetic biomarkers of the response in rectal cancer patients treated with neoadjuvant chemoradiation. Materials and Methods: Studies were retrieved by searching the PubMed database, Cochrane Library, Embase, and ISI Web of Knowledge. We conducted a meta-analysis to evaluate the association between genetic polymorphisms and the response in rectal cancer treated with neoadjuvant chemoradiation by checking odds ratios (ORs) and 95% confidence intervals (CIs). Results: Data were extracted from 5 clinical studies for this meta-analysis. The results showed that XRCC1 RS25487, XRCC1 RS179978, XRCC3 RS861539, ERCC1 RS11615 and ERCC2 RS13181 were not associated with the response in the radiotherapy-based multimodality treatment of patients with rectal cancer (p>0.05). Conclusions: This study shows that DNA repair gene common genetic polymorphisms are not significantly correlated with the radiotherapy-based multimodality treatment in rectal cancer patients.

• 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.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.

• 대한예방의학회:학술대회논문집
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• 2001.04a
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• pp.79-79
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• 2001

• 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.

• Journal of Environmental Health Sciences
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• v.37 no.6
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• pp.429-439
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• 2011

Objectives: Ethylene oxide (EtO) is classified as a human carcinogen, but EtO is still widely used to sterilize heat-sensitive materials in hospitals. Employees working around sterilizers are exposed to EtO after sterilization. The aim of the present study was to assess the exposure of EtO level, coupled with occupationally induced micronuclei from hospital workers. The influence of genetic polymorphisms of detoxifying genes (GSTT1 and GSTM1) and DNA repair genes (XRCC1 and XRCC3) on the frequencies of micronuclei in relation to exposure of EtO was also investigated. Methods: The study population was composed of 35 occupationally exposed workers to EtO, 18 student controls and 44 unexposed hospital controls in Korea. Exposure to EtO is measured by passive personal samplers. We analyzed the frequencies of micronuclei by performing cytokinesis-block micronucleus assay (CBMN assay) and GSTM1, GSTT1, XRCC1, and XRCC3 were also genotyped by performing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: The frequencies of micronuclei in EtO exposure group, student controls and hospital controls were $18.00{\pm}7.73$, $10.47{\pm}7.96$ and $13.86{\pm}6.35$ respectively and their differences were statistically significant, but no significant differences according to the level of EtO were observed. There was a dose-response relationship between the frequencies of micronuclei and cumulative dose of EtO, but no significantly differences were observed. We also investigated the influence of genetic polymorphisms (GSTM1, GSTT1, XRCC1, and XRCC3) on the frequencies of micronuclei, but there were no differences in the frequencies of micronuclei by genetic polymorphisms. Conclusions: The frequencies of micronuclei in EtO exposure group was significantly higher than control groups. A dose-response relationship was found between the level of EtO exposure and the frequencies of micronuclei, but no statistically differences were observed. We also found that the frequencies of micronuclei were increased according to cumulative EtO level. There was no association of the genetic GSTM1, GSTT1, XRCC1, and XRCC3 state with the frequency of micronuclei induced by EtO exposure.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.10
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• pp.4599-4608
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• 2016

Background: The x-ray repair cross-complementing group 3 (XRCC3) encodes a protein involved in the homologous recombination repair (HRR) pathway for double-strand DNA repair. Associations of the XRCC3 Thr241Met polymorphism with various cancers have been widely reported. However, published data on links between XRCC3 Thr241Met and gastrointestinal (GI) cancer risk are inconsistent. Objective and Methods: A meta-analysis was conducted to characterize the relationship between XRCC3 Thr241Met polymorphisms and GI cancer risk. Pooled odds ratios (ORs) and 95.0% confidence intervals were assessed using random- or fixed- effect models for 28.0 relevant articles with 30.0 studies containing 7,649.0 cases and 11,123.0 controls. Results: The results of the overall meta-analysis suggested a borderline association between the XRCC3 Thr241Met polymorphism and GI cancer susceptibility (T vs. C: OR=1.18, 9 % CI=1.0-1.4, POR=0.04; TT vs. CT+CC: OR=1.3, 95 % CI=1.0-1.6, POR=0.04). After removing studies not conforming to Hardy-Weinberg equilibrium (HWE), however, this association disappeared (T vs. C: OR=1.00, 95 % CI=0.9-1.1, POR=0.96; TT vs. CT+CC: OR=0.9, 95 % CI=0.8-1.1, POR=0.72). When stratified by ethnicity, source of controls or cancer type, although some associations between XRCC3 Thr241Met polymorphism and GI cancer susceptibility were detected, these associations no longer existed after removing studies not conforming to HWE. Conclusion: Our meta-analysis suggests that the XRCC3 Thr241Met polymorphism is not associated with risk of GI cancer based on current evidence.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.9
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• pp.4095-4099
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• 2014

The X-ray repair cross-complementing group 1 protein (XRCC1) plays important roles in the DNA base excision repair pathway which may influence the development of lung cancer. This study aimed to evaluate the potential association of the XRCC1 c.1178G>A genetic polymorphism with lung cancer risk. The created restriction site-polymerase chain reaction (CRS-PCR) and DNA sequencing methods were utilized to evaluate the XRCC1 c.1178G>A genetic polymorphism among 376 lung cancer patients and 379 controls. Associations between the genetic polymorphism and lung cancer risk were determined with an unconditional logistic regression model. Our data suggested that the distribution of allele and genotype in lung cancer patients was significantly different from that of controls. The XRCC1 c.1178G>A genetic polymorphism was associated with an increased risk of lung cancer (AA vs GG: OR=2.91, 95%CI 1.70-4.98, p<0.001; A vs G: OR=1.52, 95%CI 1.22-1.90, p<0.001). The allele A and genotype AA may contribute to risk of lung cancer. These preliminary results suggested that the XRCC1 c.1178G>A genetic polymorphism is statistically associated with lung cancer risk in the Chinese population.

• 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.