• Title, Summary, Keyword: X-ray repair cross-complementing group 1

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Association between the XRCC3 Thr241Met Polymorphism and Gastrointestinal Cancer Risk: A Meta-Analysis

  • Sahami-Fard, Mohammad Hossein;Mayali, Ali Reza Mousa;Tajehmiri, Ahmad
    • 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.

An Updated Meta-analysis on the Association of X-Ray Repair Cross Complementing Group 1 Codon 399 Polymorphism with Hepatocellular Carcinoma Risk

  • Wang, Ya-Dong;Zhai, Wen-Long;Wang, Hai-Yu;Xia, Xiang-Qun
    • 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.

Association of the XRCC1 c.1178G>A Genetic Polymorphism with Lung Cancer Risk in Chinese

  • Wang, Lei;Lin, Yong;Qi, Cong-Cong;Sheng, Bao-Wei;Fu, Tian
    • 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.

The XRCC1 Arg399Gln Genetic Polymorphism Contributes to Hepatocellular Carcinoma Susceptibility: An Updated Meta-analysis

  • Pan, Yan;Zhao, Lei;Chen, Xing-Miao;Gu, Yong;Shen, Jian-Gang;Liu, Lu-Ming
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.10
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    • pp.5761-5767
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    • 2013
  • The potential correlation of X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln polymorphism with hepatocellular carcinoma (HCC) susceptibility is ambiguous. Taking account of inconsistent results of previous meta-analyses and new emerging literatures, we conducted a meta-analysis covering 15 case-control datasets to evaluate the relationship. Relevant studies from Medline, Embase and CNKI were retrieved. A fixed-effect model or a random-effect model, depending on between-study heterogeneity, were applied to estimate the association between XRCC1 polymorphism Arg399Gln and HCC risk with the results presented as odds ratios (ORs) and 95% confidence intervals (95% CIs). In accordance with Hardy-Weinberg equilibrium, 15 studies with data for 6,556 individuals were enrolled in this systematic review. For overall HCC,thr XRCC1 polymorphism Arg399Gln was significantly associated with HCC susceptibility in a homozygote model as well as in a dominant model (G/G vs. A/A, OR=1.253, p=0.028; G/G+A/G vs. A/A, OR= 1.281, p=0.047, respectively), but not in a heterozygote model (A/G vs. A/A, OR=1.271, p=0.066) or a recessive model (G/G vs. A/G + A/A, OR= 1.049, p=0.542). Similar results were also observed on stratification analysis by ethnicity (A/G vs. A/A, OR=1.357, p=0.025; G/G vs. A/A, OR=1.310, p=0.011; G/G+A/G vs. A/A, OR= 1.371, p=0.013). However, no potential contribution of XRCC1 Arg399Gln polymorphism to HCC susceptibility in HBV/HCV subgroups was identified. No publication bias was found in this study. In conclusion, the XRCC1 Arg399Gln polymorphism contributes to HCC susceptibility. Due to the lack of studies in Western countries, further large-sample and rigorous studies are needed to validate the findings.

XRCC1-77T>C Polymorphism and Cancer Risk: A Meta-analysis

  • Wang, Yong-Gang;Zheng, Tian-Ying
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.1
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    • pp.111-115
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    • 2012
  • Variants of X-ray repair cross-complementing group 1 (XRCC1) are involved in the development of cancer, but studies investigating the association of XRCC1-77T>C polymorphism with cancer risk have reported conflicting results. To clarify the effect of the XRCC1 -77T>C polymorphism on cancer risk, we performed a meta-analysis by conducting searches of the published literature in PubMed, Embase and CBM databases. Finally, 13 studies were included into our meta-analysis, involving a total of 11, 678 individuals. Subgroup analyses were performed by ethnicity and cancer type. The results of this meta-analysis showed that there was significant association between the C variant of XRCC1-77T>C polymorphism and cancer risk in all four genetic comparison models (ORC vs. T =1.19, 95%CI 1.07-1.31, P = 0.001; OR homozygote model =1.28, 95%CI 1.07-1.52, P = 0.007; OR recessive genetic model =1.22, 95%CI 1.04-1.44, P = 0.015; OR dominant model =1.21, 95% CI 1.07-1.35, P = 0.001). In the subgroup analyses based on ethnicity, the association was still significant in the Asian population (all p values<0.001), but not in the Caucasian population (all p values > 0.05). Thus, the XRCC1 -77T>C polymorphism is associated with cancer risk, and individuals with XRCC1 -77C variant have a significantly higher cancer risk, particularly in the Asian population.

Association Between the XRCC3 T241M Polymorphism and Head and Neck Cancer Susceptibility: a Meta-analysis of Case-control Studies

  • Yin, Qing-Hua;Liu, Chuan;Li, Lian;Zu, Xu-Yu;Wang, Ya-Jie
    • 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.

Association of XRCC1 Gene Polymorphisms with Breast Cancer Susceptibility in Saudi Patients

  • Al Mutairi, Fatima Masoud;Alanazi, Mohammed;Shalaby, Manal;Alabdulkarim, Huda A.;Pathan, Akbar Ali Khan;Parine, Narasimha Reddy
    • 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.

Relationship Between Antimetabolite Toxicity and Pharmacogenetics in Turkish Cancer Patients

  • Dogan, Mutlu;Karabulut, Halil G.;Tukun, Ajlan;Demirkazik, Ahmet;Utkan, Gungor;Yalcin, Bulent;Dincol, Dilek;Akbulut, Hakan;Icli, Fikri
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.4
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    • pp.1553-1556
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    • 2012
  • Introduction: Antimetabolites may cause severe toxicity and even toxic death in cancer patients. Our aim was to evaluate the relationship between antimetabolite toxicity and pharmacogenetics in patients with severe clinical toxicity or alanine transaminase (ALT) elevation after fluorouracil (5FU), capecitabine or methotrexate administration. Patients and Methods: Cancer patients with severe antimetabolite toxicity were evaluated for methylenetetrahydrofolate reductase (MTHFR) gene C667T, thymidilate synthase (TS) gene 5´UTR variable number of tandem repeats (VNTR), dihydroprymidine dehydrogenase (DPYD) gene IVS14+1G/A, Xeroderma pigmentosum (XPD) gene Lys751Gln and X-ray repair cross-complementing group 1 (XRCC1) gene Arg399Gln polymorphisms. Results: Eighteen patients were enrolled, with a male/female ratio of 0.8. They had osteosarcoma in methotrexate group (n=7), gastrointestinal malignancies in 5FU group (n=9) and breast cancer in the capecitabine group (n=2). Mucositis and dermatitis occurred in all groups, together with ALT elevation in the methotrexate group and 2 toxic deaths were encountered. DPYD, TS, MTHFR, XPD and XRCC1 gene polymorphism rare allele frequencies were observed to be higher than in the general population. Conclusion: Pharmacogenetics might contribute to tailored therapy.

Association between the XRCC3 Thr241Met Polymorphism and Breast Cancer Risk: an Updated Meta-analysis of 36 Case-control Studies

  • Mao, Chang-Fei;Qian, Wen-Yi;Wu, Jian-Zhong;Sun, Da-Wei;Tang, Jin-Hai
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.16
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    • pp.6613-6618
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    • 2014
  • Background: The X-ray repair cross-complementing group 3 (XRCC3) is a highly suspected candidate gene for cancer susceptibility. Attention has been drawn upon associations of the XRCC3 Thr241Met polymorphism with breast cancer risk. However, the previous published findings remain controversial. Hence, we performed a meta-analysis to accurately evaluate any association between breast cancer and XRCC3 T241M (23, 812 cases and 25, 349 controls) in different inheritance models. Materials and Methods: PubMed and Web of Science databases were searched systematically until December 31, 2013 to obtain all the records evaluating the association between the XRCC3 Thr241Met polymorphism and breast cancer risk. Crude odds ratios (ORs) together with 95% confidence intervals (CIs) were used to assess the strength of associations. Results: When all eligible studies were pooled into the meta analysis of XRCC3 T241M polymorphism, a significantly increased breast cancer risk was observed in heterozygote comparison (OR=1.06, 95%CI=1.01-1.12). No significant associations were found in other models. In subgroup analysis, this polymorphism seemed to be associated with elevated breast risk in Asians. No publication bias was detected. Conclusions: This meta-analysis suggests that the T241M polymorphism confers a weakly increased breast cancer risk. A study with the larger sample size is needed to further evaluate gene-gene and gene-environment interactions of the XRCC3 T241M polymorphism with breast cancer risk.

Gene Polymorphism of XRCC1 Arg399Gln and Cervical Carcinoma Susceptibility in Asians: A Meta-analysis Based on 1,759 Cases and 2,497 Controls

  • Liu, Yi-Ting;Shi, Jing-Pu;Fu, Ling-Yu;Zhou, Bo;Wang, Hai-Long;Wu, Xiao-Mei
    • 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.