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Association between XRCC3 Thr241Met polymorphism and colorectal cancer risk

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Tumor Biology

Abstract

The x-ray repair cross-complementing group 3 (XRCC3), a member of DNA repair genes, plays a critical role in the maintenance of genome stability by homologous recombination repair for DNA double-strand breaks. The polymorphism of XRCC3 Thr241Met has been indicated to be involved in the development of some cancers, but previous individual studies on the association between XRCC3 Thr241Met polymorphism and colorectal cancer (CRC) risk have yielded conflicting and inconclusive results. To shed some light on the contradictory findings and improve our understanding of the pathogenesis of CRC, we carried out this updated meta-analysis by pooling all available publications. Databases including PubMed, Embase, Web of Science and China National Knowledge Infrastructure were searched for relevant publications. The odds ratios (ORs) with the corresponding 95 % confidence intervals (95 % CIs) were calculated to estimate the strength of the association between XRCC3 Thr241Met polymorphism and CRC risk. A total of 15 case–control studies involving 4,475 cases and 6,373 controls were included. Overall, the pooled ORs for the meta-analysis of total included studies showed no statistically significant association of XRCC3 Thr241Met polymorphism with CRC risk in any genetic model (ORMet allele vs. Thr allele = 1.17, 95 % CI 0.97–1.42, P OR = 0.102; ORMetMet vs. ThrThr = 1.32, 95 % CI 0.93–1.87, P OR = 0.121; ORThrMet vs. ThrThr = 1.17, 95 % CI 0.94–1.45, P OR = 0.150; ORMetMet + ThrMet vs. ThrThr = 1.20, 95 % CI 0.96–1.51, P OR = 0.114; ORMetMet vs. ThrThr + ThrMet = 1.37, 95 % CI 0.98–1.93, P OR = 0.065). However, in subgroup analyses stratified by source of controls and ethnicity, the XRCC3 Thr241Met polymorphism was associated with an elevated risk of CRC in the hospital-based case–control studies and the Asian population. Sensitivity analysis indicated that the findings were unlikely due to chance. This meta-analysis suggests that the XRCC3 Thr241Met polymorphism may modify the risk of CRC, particularly in Asians.

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References

  1. Pancione M, Remo A, Colantuoni V. Genetic and epigenetic events generate multiple pathways in colorectal cancer progression. Patholog Res Int. 2012;2012:509348.

    PubMed  Google Scholar 

  2. Center MM, Jemal A, Smith RA, Ward E. Worldwide variations in colorectal cancer. CA Cancer J Clin. 2009;59:366–78.

    Article  PubMed  Google Scholar 

  3. Goel A, Boland CR. Recent insights into the pathogenesis of colorectal cancer. Curr Opin Gastroenterol. 2010;26:47–52.

    Article  PubMed  CAS  Google Scholar 

  4. Yu Y, Wang W, Zhai S, Dang S, Sun M. IL6 gene polymorphisms and susceptibility to colorectal cancer: a meta-analysis and review. Mol Biol Rep. 2012;39:8457–63.

    Article  PubMed  CAS  Google Scholar 

  5. Xu D, Yan S, Yin J, Zhang P. Null genotype of GSTT1 contributes to colorectal cancer risk in Asian populations: evidence from a meta-analysis. Asian Pac J Cancer Prev. 2011;12:2279–84.

    PubMed  Google Scholar 

  6. Liu Y, Qin H, Zhang Y, Shi T, Liu B, Sun Y, et al. P53 codon 72 polymorphism and colorectal cancer: a meta-analysis of epidemiological studies. Hepatogastroenterology. 2011;58:1926–9.

    PubMed  CAS  Google Scholar 

  7. Jiang Z, Li C, Xu Y, Cai S. A meta-analysis on XRCC1 and XRCC3 polymorphisms and colorectal cancer risk. Int J Colorectal Dis. 2010;25:169–80.

    Article  PubMed  Google Scholar 

  8. Abdel-Rahman SZ, El-Zein RA. Evaluating the effects of genetic variants of DNA repair genes using cytogenetic mutagen sensitivity approaches. Biomarkers. 2011;16:393–404.

    Article  PubMed  CAS  Google Scholar 

  9. Goode EL, Ulrich CM, Potter JD. Polymorphisms in DNA repair genes and associations with cancer risk. Cancer Epidemiol Biomarkers Prev. 2002;11:1513–30.

    PubMed  CAS  Google Scholar 

  10. Manuguerra M, Saletta F, Karagas MR, Berwick M, Veglia F, Vineis P, et al. XRCC3 and XPD/ERCC2 single nucleotide polymorphisms and the risk of cancer: a HuGE review. Am J Epidemiol. 2006;164:297–302.

    Article  PubMed  Google Scholar 

  11. Pierce AJ, Johnson RD, Thompson LH, Jasin M. XRCC3 promotes homology-directed repair of DNA damage in mammalian cells. Genes Dev. 1999;13:2633–8.

    Article  PubMed  CAS  Google Scholar 

  12. Sun H, Qiao Y, Zhang X, Xu L, Jia X, Sun D, et al. XRCC3 Thr241Met polymorphism with lung cancer and bladder cancer: a meta-analysis. Cancer Sci. 2010;101:1777–82.

    Article  PubMed  CAS  Google Scholar 

  13. Economopoulos KP, Sergentanis TN. XRCC3 Thr241Met polymorphism and breast cancer risk: a meta-analysis. Breast Cancer Res Treat. 2010;121:439–43.

    Article  PubMed  CAS  Google Scholar 

  14. Han S, Zhang HT, Wang Z, Xie Y, Tang R, Mao Y, et al. DNA repair gene XRCC3 polymorphisms and cancer risk: a meta-analysis of 48 case–control studies. Eur J Hum Genet. 2006;14:1136–44.

    Article  PubMed  CAS  Google Scholar 

  15. Zhao Y, Deng X, Wang Z, Wang Q, Liu Y. Genetic polymorphisms of DNA repair genes XRCC1 and XRCC3 and risk of colorectal cancer in Chinese population. Asian Pac J Cancer Prev. 2012;13:665–9.

    Article  PubMed  Google Scholar 

  16. Gil J, Ramsey D, Stembalska A, Karpinski P, Pesz KA, Laczmanska I, et al. The C/A polymorphism in intron 11 of the XPC gene plays a crucial role in the modulation of an individual's susceptibility to sporadic colorectal cancer. Mol Biol Rep. 2012;39:527–34.

    Article  PubMed  CAS  Google Scholar 

  17. Canbay E, Cakmakoglu B, Zeybek U, Sozen S, Cacina C, Gulluoglu M, et al. Association of APE1 and hOGG1 polymorphisms with colorectal cancer risk in a Turkish population. Curr Med Res Opin. 2011;27:1295–302.

    Article  PubMed  CAS  Google Scholar 

  18. Krupa R, Sliwinski T, Wisniewska-Jarosinska M, Chojnacki J, Wasylecka M, Dziki L, et al. Polymorphisms in RAD51, XRCC2 and XRCC3 genes of the homologous recombination repair in colorectal cancer—a case control study. Mol Biol Rep. 2011;38:2849–54.

    Article  PubMed  CAS  Google Scholar 

  19. Wang J, Zhao Y, Jiang J, Gajalakshmi V, Kuriki K, Nakamura S, et al. Polymorphisms in DNA repair genes XRCC1, XRCC3 and XPD, and colorectal cancer risk: a case–control study in an Indian population. J Cancer Res Clin Oncol. 2010;136:1517–25.

    Article  PubMed  CAS  Google Scholar 

  20. Moreno V, Gemignani F, Landi S, Gioia-Patricola L, Chabrier A, Blanco I, et al. Polymorphisms in genes of nucleotide and base excision repair: risk and prognosis of colorectal cancer. Clin Cancer Res. 2006;12:2101–8.

    Article  PubMed  CAS  Google Scholar 

  21. Skjelbred CF, Saebo M, Wallin H, Nexo BA, Hagen PC, Lothe IM, et al. Polymorphisms of the XRCC1, XRCC3 and XPD genes and risk of colorectal adenoma and carcinoma, in a Norwegian cohort: a case control study. BMC Cancer. 2006;6:67.

    Article  PubMed  Google Scholar 

  22. Stern MC, Siegmund KD, Corral R, Haile RW. XRCC1 and XRCC3 polymorphisms and their role as effect modifiers of unsaturated fatty acids and antioxidant intake on colorectal adenomas risk. Cancer Epidemiol Biomarkers Prev. 2005;14:609–15.

    Article  PubMed  CAS  Google Scholar 

  23. Tranah GJ, Giovannucci E, Ma J, Fuchs C, Hankinson SE, Hunter DJ. XRCC2 and XRCC3 polymorphisms are not associated with risk of colorectal adenoma. Cancer Epidemiol Biomarkers Prev. 2004;13:1090–1.

    PubMed  CAS  Google Scholar 

  24. Krupa R, Blasiak J. An association of polymorphism of DNA repair genes XRCC1 and XRCC3 with colorectal cancer. J Exp Clin Cancer Res. 2004;23:285–94.

    PubMed  CAS  Google Scholar 

  25. Mort R, Mo L, McEwan C, Melton DW. Lack of involvement of nucleotide excision repair gene polymorphisms in colorectal cancer. Br J Cancer. 2003;89:333–7.

    Article  PubMed  CAS  Google Scholar 

  26. Yeh CC, Sung FC, Tang R, Chang-Chieh CR, Hsieh LL. Polymorphisms of the XRCC1, XRCC3, & XPD genes, and colorectal cancer risk: a case–control study in Taiwan. BMC Cancer. 2005;5:12.

    Article  PubMed  Google Scholar 

  27. Improta G, Sgambato A, Bianchino G, Zupa A, Grieco V, La Torre G, et al. Polymorphisms of the DNA repair genes XRCC1 and XRCC3 and risk of lung and colorectal cancer: a case–control study in a Southern Italian population. Anticancer Res. 2008;28:2941–6.

    PubMed  CAS  Google Scholar 

  28. Zhang JW, Meng XL. Genetic polymorphism of DNA repair gene XRCC3 and colon cancer risk. Acta Universitatis Medicinalis Anhui. 2011;46:1172–4 [Article in Chinese].

    CAS  Google Scholar 

  29. Jin MJ. Molecular epidemiology study on colorectal cancer susceptibility. Doctoral Dissertation of Zhejiang University. 2007. [Article in Chinese]

  30. Cochran WG. The comparison of percentages in matched samples. Biometrika. 1950;37:256–66.

    PubMed  CAS  Google Scholar 

  31. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60.

    Article  PubMed  Google Scholar 

  32. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.

    Article  PubMed  CAS  Google Scholar 

  33. Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22:719–48.

    PubMed  CAS  Google Scholar 

  34. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34.

    Article  PubMed  CAS  Google Scholar 

  35. Stuck AE, Rubenstein LZ, Wieland D. Bias in meta-analysis detected by a simple, graphical test. Asymmetry detected in funnel plot was probably due to true heterogeneity. BMJ. 1998;316:469.

    Article  PubMed  CAS  Google Scholar 

  36. Cecchin E, D'Andrea M, Lonardi S, Zanusso C, Pella N, Errante D, et al. A prospective validation pharmacogenomic study in the adjuvant setting of colorectal cancer patients treated with the 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX4) regimen. Pharmacogenomics J. 2012. doi:10.1038/tpj.2012.31

  37. Liu Y, Chen H, Chen L, Hu C. Prediction of genetic polymorphisms of DNA repair genes XRCC1 and XRCC3 in the survival of colorectal cancer receiving chemotherapy in the Chinese population. Hepatogastroenterology. 2012;59:977–80.

    PubMed  CAS  Google Scholar 

  38. Cecchin E, Agostini M, Pucciarelli S, De Paoli A, Canzonieri V, Sigon R, et al. Tumor response is predicted by patient genetic profile in rectal cancer patients treated with neo-adjuvant chemo-radiotherapy. Pharmacogenomics J. 2011;11:214–26.

    Article  PubMed  CAS  Google Scholar 

  39. Martinez-Balibrea E, Abad A, Aranda E, Sastre J, Manzano JL, Diaz-Rubio E, et al. Pharmacogenetic approach for capecitabine or 5-fluorouracil selection to be combined with oxaliplatin as first-line chemotherapy in advanced colorectal cancer. Eur J Cancer. 2008;44:1229–37.

    Article  PubMed  CAS  Google Scholar 

  40. Ruzzo A, Graziano F, Loupakis F, Santini D, Catalano V, Bisonni R, et al. Pharmacogenetic profiling in patients with advanced colorectal cancer treated with first-line FOLFIRI chemotherapy. Pharmacogenomics J. 2008;8:278–88.

    Article  PubMed  CAS  Google Scholar 

  41. Yeh CC, Hsieh LL, Tang R, Chang-Chieh CR, Sung FC. MS-920: DNA repair gene polymorphisms, diet and colorectal cancer risk in Taiwan. Cancer Lett. 2005;224:279–88.

    Article  PubMed  CAS  Google Scholar 

  42. Jin MJ, Chen K, Song L, Fan CH, Chen Q, Zhu YM, et al. The association of the DNA repair gene XRCC3 Thr241Met polymorphism with susceptibility to colorectal cancer in a Chinese population. Cancer Genet Cytogenet. 2005;163:38–43.

    Article  PubMed  CAS  Google Scholar 

  43. Yeh CC, Sung FC, Tang R, Chang-Chieh CR, Hsieh LL. Association between polymorphisms of biotransformation and DNA-repair genes and risk of colorectal cancer in Taiwan. J Biomed Sci. 2007;14:183–93.

    Article  PubMed  CAS  Google Scholar 

  44. Reeves SG, Meldrum C, Groombridge C, Spigelman A, Suchy J, Kurzawski G, et al. DNA repair gene polymorphisms and risk of early onset colorectal cancer in Lynch syndrome. Cancer Epidemiol. 2012;36:183–9.

    Article  PubMed  CAS  Google Scholar 

  45. Romanowicz-Makowska H, Brys M, Forma E, Maciejczyk R, Polac I, Samulak D, et al. Single nucleotide polymorphism (SNP) Thr241Met in the XRCC3 gene and breast cancer risk in Polish women. Pol J Pathol. 2012;63:121–5.

    PubMed  CAS  Google Scholar 

  46. Kiyohara C. Genetic polymorphism of enzymes involved in xenobiotic metabolism and the risk of colorectal cancer. J Epidemiol. 2000;10:349–60.

    Article  PubMed  CAS  Google Scholar 

  47. Jiang H, Tang Y, Garg HK, Parthasarathy DK, Torregrossa AC, Hord NG, et al. Concentration- and stage-specific effects of nitrite on colon cancer cell lines. Nitric Oxide. 2012;26:267–73.

    Article  PubMed  CAS  Google Scholar 

  48. Cross AJ, Ferrucci LM, Risch A, Graubard BI, Ward MH, Park Y, et al. A large prospective study of meat consumption and colorectal cancer risk: an investigation of potential mechanisms underlying this association. Cancer Res. 2010;70:2406–14.

    Article  PubMed  CAS  Google Scholar 

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  1. Key Laboratory of Cancer Prevention and Therapy, Department of Radiation Therapy, TianJin Medical University Cancer Institute and Hospital, Tianjin, 300060, China

    ZhiZhen Wang & Wencheng Zhang

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Wang, Z., Zhang, W. Association between XRCC3 Thr241Met polymorphism and colorectal cancer risk. Tumor Biol. 34, 1421–1429 (2013). https://doi.org/10.1007/s13277-012-0639-1

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