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Base excision repair genes XRCC1 and APEX1 and the risk for prostate cancer

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Abstract

Prostate cancer is the second cause of cancer death in Brazilian men. One of the relevant phenomena to the inherited susceptibility is the presence of allelic variants in genes involved with the DNA repair pathway. The aim of this study was to analyze the frequencies of prevalent, heterozygous and rare genotypes of the base excision repair genes APEX1 and XRCC1 in a case–control study and relate the genotypes with tumoral aggressiveness. DNA from peripheral blood of 172 patients and 172 controls were analyzed by RFLP-PCR method. The polymorphisms were also evaluated in relation to clinical and pathological parameters. The OR (Odds Ratio) and confidence interval (CI = 95%) were used in the association study and the Chi-square and ANOVA tests for the evaluation of histopathological parameters. The rare genotypes frequencies of the gene APEX1 increased the risk for the development of prostate cancer (OR = 1.68 95% CI 1.10–2.58). No association was found for the gene XRCC1 (OR = 0.82 95% CI 0.53–1.27). The combined analysis for both genes did not show association with this neoplasia (OR = 1.27 95% CI 0.79–20.5). The relationship of XRCC1 and APEX1 genotypes with cancer aggressiveness through the correlation with histopathological parameters, did not find any association. Our results suggest that the polymorphism in the gene APEX1 may be indicated as a potential marker for prostate cancer risk.

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References

  1. INCA: Instituto Nacional do Câncer. http://www.inca.gov.br/estimativa/2010. Accessed 26 February 2010

  2. Hirata H, Hinoda Y, Tanaka Y, Okayama N, Suehiro Y, Kawamoto K, Kikuno N, Majid S, Vejdani K, Dahiya R (2007) Polymorphisms of DNA repair genes are risk factors for prostate cancer. Eur J Cancer 43(2):231–237

    Article  CAS  PubMed  Google Scholar 

  3. Shen MR, Jones IM, Morenweiser H (1998) Nonconservative amino acid substitution variants exist at polymorphic frequency in DNA repair genes in healthy humans. Cancer Res 58:604–608

    CAS  PubMed  Google Scholar 

  4. Xi T, Jones IM, Mohrenweiser HW (2004) Many amino acid substitution variants identified in DNA repair genes during human population screenings are predicted to impact protein function. Genomics 83:970–979

    Article  CAS  PubMed  Google Scholar 

  5. Hung RJ, Hall J, Brennan P, Boffetta P (2005) Genetic polymorphisms in the base excision repair pathway and cancer risk: a HuGE review. Am J Epidemiol 162(10):925–942

    Article  PubMed  Google Scholar 

  6. Kubota Y, Nash RA, Klungland A, Schar P, Barnes DE, Lindahl T (1996) Reconstitution of DNA base excision-repair with purified human proteins: interaction between DNA polymerase b and the XRCC1 protein. EMBO J 15:6662–6670

    CAS  PubMed  Google Scholar 

  7. Thompson LH, West MG (2000) XRCC1 keeps DNA from getting stranded. Mutat Res 459:1–18

    CAS  PubMed  Google Scholar 

  8. Caldecott KW, Aoufouchi S, Johnson P, Shall S (1996) XRCC1 polypeptide interacts with DNA polymerase b and possibly poly(ADP-ribose) polymerase, and DNA ligase III is a novel molecular ‘nick-sensor’ in vitro. Nucleic Acids Res 24:4387–4394

    Article  CAS  PubMed  Google Scholar 

  9. Xu Z, Hua LX, Qian LX, Yang J, Wang XR, Zhang W, Wu HF (2007) Relationship between XRCC1 polymorphisms and susceptibility to prostate cancer in men from Han, Southern China. Asian J Androl 9(3):331–338

    Article  CAS  PubMed  Google Scholar 

  10. Rybicki BA, Conti DV, Moreira A, Cicek M, Casey G, Witte JS (2004) DNA repair gene XRCC1 and XPD polymorphisms and risk of prostate cancer. Cancer Epidel Biom Prev 13(1):23–29

    Article  CAS  Google Scholar 

  11. Chen L, Ambrosone CB, Lee J, Sellers TA, Pow-sang J, Park JY, Popanda O (2006) Association between polymorphisms in the DNA repair genes XRCC1 and APE1, and the risk of prostate cancer in white and black Americans. J Urol 175:108–112

    Article  CAS  PubMed  Google Scholar 

  12. Casse C, Hu YC, Ahrendt SA (2003) The XRCC1 codon 399Gln allele is associated with adenine to guanine p53 mutations in non-small cell lung cancer. Mutat Res 528:19–27

    CAS  PubMed  Google Scholar 

  13. Duell EJ, Wiencke JK, Cheng TJ, Varkonyi A, Zuo ZF, Ashok TD et al (2000) Polymorphisms in the DNA repair genes XRCC1 and ERCC2 and biomarkers of DNA damage in human blood mononuclear cells. Carcinogenesis 21:965–971

    Article  CAS  PubMed  Google Scholar 

  14. Lunn RM, Langlois RG, Hsieh LL, Thompson CL, Bell DA (1999) XRCC1 polymorphisms: effects on aflatoxin B1-DNA adducts and glycophorin A variant frequency. Cancer Res 59:2557–2561

    CAS  PubMed  Google Scholar 

  15. Chen DS, Herman T, Demple B (1991) Two distinct human DNA diesterases that hydrolyze 3V-blocking deoxyribose fragments from oxidized DNA. Nucleic Acids Res 9(21):5907–5914

    Article  Google Scholar 

  16. Demple B, Harrison L (1994) Repair of oxidative damage to DNA: enzymology and biology. Ann Rev Biochem 63:915–948

    Article  CAS  PubMed  Google Scholar 

  17. Evans AR, Limp-Foster M, Kelley MR (2000) Going APE over ref-1. Mutat Res 461(2):83–108

    CAS  PubMed  Google Scholar 

  18. Hu JJ, Smith TR, Miller MS, Mohrenweiser HW, Golden A, Case LD (2001) Amino acid substitution variants of APE1 and XRCC1 genes associated with ionizing radiation sensitivity. Carcinogenesis 22(6):917–922

    Article  CAS  PubMed  Google Scholar 

  19. Kelley MR, Cheng L, Foster R, Tritt R, Jiang J, Broshears J, koch M (2001) Elevated and altered expression of the multifunctional DNA base excision repair and redox enzyme Ape1/ref-1 in prostate cancer. Clin Cancer Res 7(4):824–830

    CAS  PubMed  Google Scholar 

  20. Gu D, Wang M, Wang M, Zhang Z, Chen J (2009) The DNA repair gene APE1 T1349G polymorphism and cancer risk: a meta-analysis of 27 case-control studies. Mutagenesis 24(6):507–512

    Article  CAS  PubMed  Google Scholar 

  21. Carrano AV, Natarajana AT (1988) International commission for protection against environmental mutagens and carcinogens ICPEMC publication no. 14. Considerations for population monitoring using cytogenetic techniques. Mutat Res 204:379–406

    Article  CAS  PubMed  Google Scholar 

  22. Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extraction DNA from human nucleated cell. Nucleic Acids Res 16:1215

    Article  CAS  PubMed  Google Scholar 

  23. Gleason DF (1992) Histologic grading of prostate cancer: a perspective. Human Path 23:273–279

    Article  CAS  Google Scholar 

  24. AJCC/UICC-American Joint Committee on Cancer/International Union Against Cancer. http://www.uicc.org. Accessed 16 June 2009

  25. D’Amico AV, Whittington R, Malkowicz SB, Ondurulia J, Chen MH, Tomaszewski JE (1998) The combination of preoperative prostate specific antigen and postoperative pathological findings to predict prostate specific antigen outcome in clinically localized prostate cancer. J Urol 160(6 Pt 1):2096–2101

    PubMed  Google Scholar 

  26. Ayres M, Ayres Jr M, Ayres DL, Santos AS. BioEstat Version.5. Civil Society MCT Mamirauá – CNPq. Belem, Pará, Brasil

  27. Braile DM and Godoy MF. Odds Ration Calculater. Braile Biomedics. São José do Rio Preto, São Paulo, Brasil

  28. Weitzman SA, Gordon LI (1990) Inflammation and cancer: role of phagocyte-generated oxidants in carcinogenesis. Blood 76:655–663

    CAS  PubMed  Google Scholar 

  29. Bartsch H, Frank N (1996) Blocking the endogenous formation of N-nitroso compounds and related carcinogens. IARC Sci Publ 139:189–201

    CAS  PubMed  Google Scholar 

  30. Shinmura K, Yamaguchi S, Saitoh T et al (2001) Somatic mutations and single nucleotide polymorphisms of base excision repair genes involved in the repair of hydroxyguanine in damaged DNA. Cancer Lett 166(1):65–69

    Article  CAS  PubMed  Google Scholar 

  31. Gao R, Price DK, Sissung T, Reed E, Figg WD (2008) Ethnic disparities in Americans of European descent versus Americans of African descent related to polymorphic ERCC1, ERCC2, XRCC1, and PARP1. Mol Cancer Ther 7(5):1246–1250

    Article  CAS  PubMed  Google Scholar 

  32. Parra FC, Amado RC, Lambertucci JR, Rocha J, Antunes CM, Pena SDJ (2002) Color and genomic ancestry in Brazilians. Genetics 100:177–182

    Google Scholar 

  33. Vidal AE, Boiteux S, Hickson I-D, Radicella J-P (2001) XRCC1 coordinates the initial and late stages of DNA abasic site repair through protein-protein interactions. EMBO J 20:6530–6539

    Article  CAS  PubMed  Google Scholar 

  34. Geng J, Zhang Q, Zhu C, Wang J, Chen L (2009) XRCC1 genetic polymorphism Arg399Gln and prostate cancer risk: a meta-analysis. Urology 74(3):648–653

    Article  PubMed  Google Scholar 

  35. Farkasova T, Gurska S, Witkovsky V, Gabelova A (2008) Significance of amino acid substitution variants of DNA repair genes in radiosusceptibility of cervical cancer patients; a pilot study. Neoplasma 55(4):330–337

    CAS  PubMed  Google Scholar 

  36. Kasahara M, Osawa K, Yoshida K, Miyaishi A, Osawa Y, Inoue N, Tsutou A, Tabuchi Y, Tanaka K, Yamamoto M, Shimada E, Takahashi J (2008) Association of MUTYH Gln324His and APEX1 Asp148Glu with colorectal cancer and smoking in a Japanese population. J Exp Clin Cancer Res 27:49

    Article  PubMed  Google Scholar 

  37. Ito H, Matsuo K, Hamajima N, Mitsudomi T, Sugiura T, Saito T, Yasue T, Lee KM, Kang D, Yoo KY, Sato S, Ueda R, Tajima K (2004) Gene-environment interactions between the smoking habit and polymorphisms in the DNA repair genes, APE1 Asp148Glu and XRCC1 Arg399Gln, in Japanese lung cancer risk. Carcinogenesis 25(8):1395–1401

    Article  CAS  PubMed  Google Scholar 

  38. Hamdy FC (2001) Prognostic and predictive factors in prostate cancer. Cancer Treat Rev 27(3):143–151

    Article  CAS  PubMed  Google Scholar 

  39. Chatelard PP (2002) Standards options and recommendations for the management of prostate cancer: therapeutic decision criteria. Bull Cancer 89(6):619–634

    PubMed  Google Scholar 

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Acknowledgments

This work was supported by Fundação Araucária. The authors would like to thank the CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) for supporting fellowships of Kuasne H. and Rodrigues IS, CNPq/PQ (Conselho Nacional de Desenvolvimento Científico e Tecnológico) for awarding a grant to Cólus IMS and to the Hospital do Câncer de Londrina (HCL), Irmandade Santa Casa de Londrina and CISMEPAR for the samples from patients and controls.

Conflict of interest

All the authors of this article declare have no conflict of interest.

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Authors and Affiliations

  1. Department of General Biology, Biological Science Center, Londrina State University, Londrina, PR, Brazil

    H. Kuasne, I. S. Rodrigues, R. Losi-Guembarovski, M. B. Reis, H. M. Matsuda & I. M. S. Cólus

  2. Londrina Hospital of Cancer, Londrina, PR, Brazil

    P. E. Fuganti, E. P. Gregório & F. Libos Junior

  3. Department of Pathology, Clinical and Toxicological Analysis, Health Science Center, Londrina State University, Londrina, PR, Brazil

    M. O. Kishima

  4. Department of Clinical Surgery, Health Science Center, Londrina State University, Londrina, PR, Brazil

    M. A. F. Rodrigues

  5. Universidade Estadual de Londrina – UEL, Rodovia Celso Garcia Cid, PR (445), Km 380, CEP 86051-990, Londrina, Paraná, Brazil

    H. Kuasne

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  1. H. Kuasne
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Correspondence to H. Kuasne.

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Kuasne, H., Rodrigues, I.S., Losi-Guembarovski, R. et al. Base excision repair genes XRCC1 and APEX1 and the risk for prostate cancer. Mol Biol Rep 38, 1585–1591 (2011). https://doi.org/10.1007/s11033-010-0267-z

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  • DOI: https://doi.org/10.1007/s11033-010-0267-z

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