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Polymorphisms in genes of APE1, PARP1, and XRCC1: risk and prognosis of colorectal cancer in a Northeast Chinese population

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Abstract

Base excision repair (BER) pathway plays critical role in maintaining genome integrity. Polymorphisms in BER genes which modulate the DNA repair capacity may affect the susceptibility and prognosis of cancer. We conducted a case–control study and followed up the cases to explore the associations between BER genes polymorphisms and the risk and prognosis of colorectal cancer (CRC). This study included 451 CRC patients and 631 controls. Four single-nucleotide polymorphisms (SNPs) in genes of apurinic/apyrimidinic endonuclease-1 (APE1), ADP-ribosyltransferase (ADPRT, also known as PARP1), and X-ray repair cross-complementing groups 1 (XRCC1) were tested by PCR–RFLP. Odds ratio (OR), hazard ratio (HR), and their 95 % confidence intervals (CIs) were calculated by unconditional logistic regression and Cox proportional hazard model. PARP1 762 recessive model (OR = 1.57, 95 % CI 1.12–2.20) and XRCC1 194 dominant model (OR = 1.45, 95 % CI 1.12–1.88) were associated with increased CRC risk. A significant increasing trend for the risk of CRC was detected with the increasing number of putative risk genotypes (P trend = 0.00). However, no association was found between these four SNPs and the prognosis of CRC. In conclusion, APE1 (Asp148Glu), PARP1 (Ala762Val), and XRCC1 (Arg399Gln, Arg194Trp) were associated with the susceptibility to CRC, but were not associated with the prognosis of CRC.

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References

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2008;61(2):69–90. doi:10.3322/caac.20107.

    Article  Google Scholar 

  2. Sargent DJ, Wieand HS, Haller DG, Gray R, Benedetti JK, Buyse M, Labianca R, Seitz JF, O’Callaghan CJ, Francini G, Grothey A, O’Connell M, Catalano PJ, Blanke CD, Kerr D, Green E, Wolmark N, Andre T, Goldberg RM, De Gramont A. Disease-free survival versus overall survival as a primary end point for adjuvant colon cancer studies: individual patient data from 20,898 patients on 18 randomized trials. J Clin Oncol. 2005;23(34):8664–70. doi:10.1200/JCO.2005.01.6071.

    Article  PubMed  Google Scholar 

  3. Parikh SS, Mol CD, Tainer JA. Base excision repair enzyme family portrait: integrating the structure and chemistry of an entire DNA repair pathway. Structure. 1997;5(12):1543–50.

    Article  PubMed  CAS  Google Scholar 

  4. Gossage L, Perry C, Abbotts R, Madhusudan S. Base excision repair factors are promising prognostic and predictive markers in cancer. Curr Mol Pharmacol. 2012;5(1):115–24.

    PubMed  CAS  Google Scholar 

  5. Zhou B, Shan H, Su Y, Xia K, Shao X, Mao W, Shao Q. The association of APE1-656T > G and 1349 T > G polymorphisms and cancer risk: a meta-analysis based on 37 case-control studies. BMC Cancer. 2011;11:521. doi:10.1186/1471-2407-11-521.

  6. Yu H, Ma H, Yin M, Wei Q. Association between PARP-1 V762A polymorphism and cancer susceptibility: a meta-analysis. Genet Epidemiol. 2012;36(1):56–65. doi:10.1002/gepi.20663.

    Google Scholar 

  7. Stern MC, Butler LM, Corral R, Joshi AD, Yuan JM, Koh WP, Yu MC. Polyunsaturated fatty acids, DNA repair single nucleotide polymorphisms and colorectal cancer in the Singapore Chinese Health Study. J Nutrigenet Nutrigenomics. 2009;2(6):273–9. doi:10.1159/000308467.

    Article  PubMed  CAS  Google Scholar 

  8. Brevik A, Joshi AD, Corral R, Onland-Moret NC, Siegmund KD, Le Marchand L, Baron JA, Martinez ME, Haile RW, Ahnen DJ, Sandler RS, Lance P, Stern MC. Polymorphisms in base excision repair genes as colorectal cancer risk factors and modifiers of the effect of diets high in red meat. Cancer Epidemiol Biomarkers Prev;19(12):3167–3173. doi:10.1158/1055-9965.EPI-10-0606.

  9. Zhang Q, Li Y, Li X, Zhou W, Shi B, Chen H, Yuan W. PARP-1 Val762Ala polymorphism, CagA + H. pylori infection and risk for gastric cancer in Han Chinese population. Mol Biol Rep. 2009;36(6):1461–1467. doi:10.1007/s11033-008-9336-y.

  10. 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(2):183–93. doi:10.1007/s11373-006-9139-x.

    Article  PubMed  CAS  Google Scholar 

  11. Wang J, Zhao Y, Jiang J, Gajalakshmi V, Kuriki K, Nakamura S, Akasaka S, Ishikawa H, Suzuki S, Nagaya T, Tokudome S. 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;136(10):1517–1525. doi:10.1007/s00432-010-0809-8.

  12. Kasahara M, Osawa K, Yoshida K, Miyaishi A, Osawa Y, Inoue N, Tsutou A, Tabuchi Y, Tanaka K, Yamamoto M, Shimada E, Takahashi J. Association of MUTYH Gln324His and APEX1 Asp148Glu with colorectal cancer and smoking in a Japanese population. J Exp Clin Cancer Res. 2008;27:49. doi:10.1186/1756-9966-27-49.

    Article  PubMed  Google Scholar 

  13. Pardini B, Naccarati A, Novotny J, Smerhovsky Z, Vodickova L, Polakova V, Hanova M, Slyskova J, Tulupova E, Kumar R, Bortlik M, Barale R, Hemminki K, Vodicka P. DNA repair genetic polymorphisms and risk of colorectal cancer in the Czech Republic. Mutat Res. 2008;638(1–2):146–53. doi:10.1016/j.mrfmmm.2007.09.008.

    PubMed  CAS  Google Scholar 

  14. Curtin K, Samowitz WS, Wolff RK, Ulrich CM, Caan BJ, Potter JD, Slattery ML. Assessing tumor mutations to gain insight into base excision repair sequence polymorphisms and smoking in colon cancer. Cancer Epidemiol Biomarkers Prev. 2009;18(12):3384–8. doi:10.1158/1055-9965.EPI-09-0955.

    Article  PubMed  CAS  Google Scholar 

  15. Berndt SI, Huang WY, Fallin MD, Helzlsouer KJ, Platz EA, Weissfeld JL, Church TR, Welch R, Chanock SJ, Hayes RB. Genetic variation in base excision repair genes and the prevalence of advanced colorectal adenoma. Cancer Res. 2007;67(3):1395–404. doi:10.1158/0008-5472.CAN-06-1390.

    Article  PubMed  CAS  Google Scholar 

  16. Stern MC, Conti DV, Siegmund KD, Corral R, Yuan JM, Koh WP, Yu MC. DNA repair single-nucleotide polymorphisms in colorectal cancer and their role as modifiers of the effect of cigarette smoking and alcohol in the Singapore Chinese Health Study. Cancer Epidemiol Biomarkers Prev. 2007;16(11):2363–72. doi:10.1158/1055-9965.EPI-07-0268.

    Article  PubMed  CAS  Google Scholar 

  17. Hung RJ, Hall J, Brennan P, Boffetta P. Genetic polymorphisms in the base excision repair pathway and cancer risk: a HuGE review. Am J Epidemiol. 2005;162(10):925–42. doi:10.1093/aje/kwi318.

    Article  PubMed  Google Scholar 

  18. Hu XB, Feng Z, Fan YC, Xiong ZY, Huang QW. Polymorphisms in DNA repair gene XRCC1 and increased genetic susceptibility to glioma. Asian Pac J Cancer Prev. 2011;12(11):2981–2984.

    Google Scholar 

  19. Chen S, Tang D, Xue K, Xu L, Ma G, Hsu Y, Cho SS. DNA repair gene XRCC1 and XPD polymorphisms and risk of lung cancer in a Chinese population. Carcinogenesis. 2002;23(8):1321–5.

    Article  PubMed  Google Scholar 

  20. Chiang FY, Wu CW, Hsiao PJ, Kuo WR, Lee KW, Lin JC, Liao YC, Juo SH. Association between polymorphisms in DNA base excision repair genes XRCC1, APE1, and ADPRT and differentiated thyroid carcinoma. Clin Cancer Res. 2008;14(18):5919–24. doi:10.1158/1078-0432.CCR-08-0906.

    Article  PubMed  CAS  Google Scholar 

  21. 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. doi:10.1186/1471-2407-5-12.

    Article  PubMed  Google Scholar 

  22. Moreno V, Gemignani F, Landi S, Gioia-Patricola L, Chabrier A, Blanco I, Gonzalez S, Guino E, Capella G, Canzian F. Polymorphisms in genes of nucleotide and base excision repair: risk and prognosis of colorectal cancer. Clin Cancer Res. 2006;12(7 Pt 1):2101–8. doi:10.1158/1078-0432.CCR-05-1363.

    Article  PubMed  CAS  Google Scholar 

  23. Abdel-Rahman SZ, Soliman AS, Bondy ML, Omar S, El-Badawy SA, Khaled HM, Seifeldin IA, Levin B. Inheritance of the 194Trp and the 399Gln variant alleles of the DNA repair gene XRCC1 are associated with increased risk of early-onset colorectal carcinoma in Egypt. Cancer Lett. 2000;159(1):79–86.

    Article  PubMed  CAS  Google Scholar 

  24. Bigler J, Ulrich CM, Kawashima T, Whitton J, Potter JD. DNA repair polymorphisms and risk of colorectal adenomatous or hyperplastic polyps. Cancer Epidemiol Biomarkers Prev. 2005;14(11 Pt 1):2501–8. doi:10.1158/1055-9965.EPI-05-0270.

    Article  PubMed  CAS  Google Scholar 

  25. Zeng FR, Ling Y, Yang J, Tian XC, Yang X, Luo RC. X-ray repair cross-complementing group 1 Arg399Gln gene polymorphism and susceptibility to colorectal cancer: a meta-analysis. Tumour Biol. doi:10.1007/s13277-012-0581-2.

  26. Naccarati A, Pardini B, Hemminki K, Vodicka P. Sporadic colorectal cancer and individual susceptibility: a review of the association studies investigating the role of DNA repair genetic polymorphisms. Mutat Res. 2007;635(2–3):118–45. doi:10.1016/j.mrrev.2007.02.001.

    PubMed  CAS  Google Scholar 

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Acknowledgments

We are especially grateful to all of the individuals who conducted this research. This work was supported by National Natural Science Foundation of China (NSFC 30972539).

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Correspondence to Fan Wang or Yashuang Zhao.

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Li, Y., Li, S., Wu, Z. et al. Polymorphisms in genes of APE1, PARP1, and XRCC1: risk and prognosis of colorectal cancer in a Northeast Chinese population. Med Oncol 30, 505 (2013). https://doi.org/10.1007/s12032-013-0505-z

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