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DNA double-strand break repair gene XRCC7 genotypes were associated with hepatocellular carcinoma risk in Taiwanese males and alcohol drinkers

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Tumor Biology

Abstract

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide, the prevalence and mortality rates of which are very high in Taiwan. The study aimed at evaluating the contribution of XRCC7 G6721T, together with cigarette smoking and alcohol drinking lifestyles, to the risk of HCC. In this hospital-based case-control study, the association of XRCC7 single nucleotide polymorphism G6721T with HCC risk was examined by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) among 298 HCC patients and 889 age- and gender-matched healthy controls. The results showed that the percentages of TT, GT, and GG XRCC7 G6721T were 53.0, 41.3, and 5.7 % in the HCC patient group and 48.9, 43.1, and 8.0 % in the non-cancer control group, respectively. We have further stratified the populations by genders, cigarette smoking, and alcohol drinking status to investigate their combinative contributions with XRCC7 G6721T genotype to HCC risk. The results showed that the GG genotype of XRCC7 G6721T conducted a protective effect on HCC susceptibility which was obvious among males and drinkers, but not females, smokers, non-smokers, or non-drinkers (p = 0.0058, 0.0069, 0.1564, 0.2469, 0.9354, and 0.3416, respectively). Our results suggested that the GG and GT genotypes of X-ray repair cross-complementing group 7 (XRCC7) G6721T had no effect on HCC risk to the whole population, but had a protective effect on HCC risk among males and alcohol drinkers.

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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. 2011;61(2):69–90.

    Article  PubMed  Google Scholar 

  2. Franceschi S, Montella M, Polesel J, La Vecchia C, Crispo A, Dal Maso L, et al. Hepatitis viruses, alcohol, and tobacco in the etiology of hepatocellular carcinoma in Italy. Cancer Epidemiol Biomarkers Prev. 2006;15(4):683–9.

    Article  CAS  PubMed  Google Scholar 

  3. Chuang SC, La Vecchia C, Boffetta P. Liver cancer: descriptive epidemiology and risk factors other than HBV and HCV infection. Cancer Lett. 2009;286(1):9–14.

    Article  CAS  PubMed  Google Scholar 

  4. Trichopoulos D, Bamia C, Lagiou P, Fedirko V, Trepo E, Jenab M, et al. Hepatocellular carcinoma risk factors and disease burden in a European cohort: a nested case–control study. J Natl Cancer Inst. 2011;103(22):1686–95.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Karran P. DNA double strand break repair in mammalian cells. Curr Opin Genet Dev. 2000;10(2):144–50.

    Article  CAS  PubMed  Google Scholar 

  6. Valerie K, Povirk LF. Regulation and mechanisms of mammalian double-strand break repair. Oncogene. 2003;22(37):5792–812.

    Article  CAS  PubMed  Google Scholar 

  7. Sipley JD, Menninger JC, Hartley KO, Ward DC, Jackson SP, Anderson CW. Gene for the catalytic subunit of the human DNA-activated protein kinase maps to the site of the XRCC7 gene on chromosome 8. Proc Natl Acad Sci U S A. 1995;92(16):7515–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Ferguson DO, Sekiguchi JM, Chang S, Frank KM, Gao Y, DePinho RA, et al. The nonhomologous end-joining pathway of DNA repair is required for genomic stability and the suppression of translocations. Proc Natl Acad Sci U S A. 2000;97(12):6630–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Singleton BK, Priestley A, Steingrimsdottir H, Gell D, Blunt T, Jackson SP, et al. Molecular and biochemical characterization of xrs mutants defective in Ku80. Mol Cell Biol. 1997;17(3):1264–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Wang LE, Bondy ML, Shen H, El-Zein R, Aldape K, Cao Y, et al. Polymorphisms of DNA repair genes and risk of glioma. Cancer Res. 2004;64(16):5560–3.

    Article  CAS  PubMed  Google Scholar 

  11. Hirata H, Hinoda Y, Matsuyama H, Tanaka Y, Okayama N, Suehiro Y, et al. Polymorphisms of DNA repair genes are associated with renal cell carcinoma. Biochem Biophys Res Commun. 2006;342(4):1058–62.

    Article  CAS  PubMed  Google Scholar 

  12. Hirata H, Hinoda Y, Tanaka Y, Okayama N, Suehiro Y, Kawamoto K, et al. Polymorphisms of DNA repair genes are risk factors for prostate cancer. Eur J Cancer. 2007;43(2):231–7.

    Article  CAS  PubMed  Google Scholar 

  13. Liu Y, Zhang H, Zhou K, Chen L, Xu Z, Zhong Y, et al. Tagging SNPs in non-homologous end-joining pathway genes and risk of glioma. Carcinogenesis. 2007;28(9):1906–13.

    Article  CAS  PubMed  Google Scholar 

  14. Hu Z, Liu H, Wang H, Miao R, Sun W, Jin G, et al. Tagging single nucleotide polymorphisms in phosphoinositide-3-kinase-related protein kinase genes involved in DNA damage “checkpoints” and lung cancer susceptibility. Clin Cancer Res. 2008;14(9):2887–91.

    Article  CAS  PubMed  Google Scholar 

  15. Siraj AK, Al-Rasheed M, Ibrahim M, Siddiqui K, Al-Dayel F, Al-Sanea O, et al. RAD52 polymorphisms contribute to the development of papillary thyroid cancer susceptibility in Middle Eastern population. J Endocrinol Invest. 2008;31(10):893–9.

    Article  CAS  PubMed  Google Scholar 

  16. Wang SY, Peng L, Li CP, Li AP, Zhou JW, Zhang ZD, et al. Genetic variants of the XRCC7 gene involved in DNA repair and risk of human bladder cancer. Int J Urol. 2008;15(6):534–9.

    Article  CAS  PubMed  Google Scholar 

  17. Bhatti P, Struewing JP, Alexander BH, Hauptmann M, Bowen L, Mateus-Pereira LH, et al. Polymorphisms in DNA repair genes, ionizing radiation exposure and risk of breast cancer in U.S. Radiologic technologists. Int J Cancer. 2008;122(1):177–82.

    Article  CAS  PubMed  Google Scholar 

  18. McKean-Cowdin R, Barnholtz-Sloan J, Inskip PD, Ruder AM, Butler M, Rajaraman P, et al. Associations between polymorphisms in DNA repair genes and glioblastoma. Cancer Epidemiol Biomarkers Prev. 2009;18(4):1118–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Gangwar R, Ahirwar D, Mandhani A, Mittal RD. Do DNA repair genes OGG1, XRCC3 and XRCC7 have an impact on susceptibility to bladder cancer in the North Indian population? Mutat Res. 2009;680(1–2):56–63.

    Article  CAS  PubMed  Google Scholar 

  20. Mandal RK, Kapoor R, Mittal RD. Polymorphic variants of DNA repair gene XRCC3 and XRCC7 and risk of prostate cancer: a study from North Indian population. DNA Cell Biol. 2010;29(11):669–74.

    Article  CAS  PubMed  Google Scholar 

  21. Long XD, Yao JG, Huang YZ, Huang XY, Ban FZ, Yao LM, et al. DNA repair gene XRCC7 polymorphisms (rs#7003908 and rs#10109984) and hepatocellular carcinoma related to AFB1 exposure among Guangxi population, China. Hepatol Res. 2011;41(11):1085–93.

    Article  CAS  PubMed  Google Scholar 

  22. Al-Hadyan KS, Al-Harbi NM, Al-Qahtani SS, Alsbeih GA. Involvement of single-nucleotide polymorphisms in predisposition to head and neck cancer in Saudi Arabia. Genet Test Mol Biomarkers. 2012;16(2):95–101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Nasiri M, Saadat I, Omidvari S, Saadat M. Genetic variation in DNA repair gene XRCC7 (G6721T) and susceptibility to breast cancer. Gene. 2012;505(1):195–7.

    Article  CAS  PubMed  Google Scholar 

  24. Hsu CM, Yang MD, Chang WS, Jeng LB, Lee MH, Lu MC, et al. The contribution of XRCC6/Ku70 to hepatocellular carcinoma in Taiwan. Anticancer Res. 2013;33(2):529–35.

    CAS  PubMed  Google Scholar 

  25. Wang Z, Lin H, Hua F, Hu ZW. Repairing DNA damage by XRCC6/KU70 reverses TLR4-deficiency-worsened HCC development via restoring senescence and autophagic flux. Autophagy. 2013;9(6):925–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Machida K, McNamara G, Cheng KT, Huang J, Wang CH, Comai L, et al. Hepatitis C virus inhibits DNA damage repair through reactive oxygen and nitrogen species and by interfering with the ATM-NBS1/Mre11/Rad50 DNA repair pathway in monocytes and hepatocytes. J Immunol. 2010;185(11):6985–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Tsai CW, Chang WS, Liu JC, Tsai MH, Lin CC, Bau DT. Contribution of DNA double-strand break repair gene XRCC3 genotypes to oral cancer susceptibility in Taiwan. Anticancer Res. 2014;34(6):2951–6.

    CAS  PubMed  Google Scholar 

  28. Tsai CW, Chang WS, Lin KC, Shih LC, Tsai MH, Hsiao CL, et al. Significant association of Interleukin-10 genotypes and oral cancer susceptibility in Taiwan. Anticancer Res. 2014;34(7):3731–7.

    CAS  PubMed  Google Scholar 

  29. Huang CY, Chang WS, Shui HA, Hsieh YH, Loh CH, Wang HC, et al. Evaluation of the contribution of methylenetetrahydrofolate reductase genotypes to Taiwan breast cancer. Anticancer Res. 2014;34(8):4109–15.

    CAS  PubMed  Google Scholar 

  30. Bau DT, Fu YP, Chen ST, Cheng TC, Yu JC, Wu PE, et al. Breast cancer risk and the DNA double-strand break end-joining capacity of nonhomologous end-joining genes are affected by BRCA1. Cancer Res. 2004;64(14):5013–9.

    Article  CAS  PubMed  Google Scholar 

  31. Gottlieb TM, Jackson SP. The DNA-dependent protein kinase: requirement for DNA ends and association with Ku antigen. Cell. 1993;72(1):131–42.

    Article  CAS  PubMed  Google Scholar 

  32. Jackson SP. DNA-dependent protein kinase. Int J Biochem Cell Biol. 1997;29(7):935–8.

    Article  CAS  PubMed  Google Scholar 

  33. Hsu CM, Yang MD, Tsai CW, Ho CY, Chang WS, Chang SC, et al. The contribution of caveolin-1 genotype and phenotype to hepatocellular carcinoma. Anticancer Res. 2013;33(2):671–7.

    CAS  PubMed  Google Scholar 

  34. Chang WS, Yang MD, Tsai CW, Cheng LH, Jeng LB, Lo WC, et al. Association of cyclooxygenase 2 single-nucleotide polymorphisms and hepatocellular carcinoma in Taiwan. Chin J Physiol. 2012;55(1):1–7.

    Article  CAS  PubMed  Google Scholar 

  35. Pelucchi C, Gallus S, Garavello W, Bosetti C, La Vecchia C. Alcohol and tobacco use, and cancer risk for upper aerodigestive tract and liver. Eur J Cancer Prev. 2008;17(4):340–4.

    Article  PubMed  Google Scholar 

  36. Xiao M, Shen Y, Chen L, Liao Z, Wen F. The rs7003908 (T>G) polymorphism in the XRCC7 gene and the risk of cancers. Mol Biol Rep. 2014;41(6):3577–82.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We appreciate Hong-Xue Ji, Chieh-Lun Hsiao, Chia-En Miao, and the Tissue Bank of China Medical University Hospital for their excellent technical assistance. This study was supported by research grants from Terry Fox Cancer Research Foundation and the Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence (MOHW103-TDU-B-212-113002).

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Authors and Affiliations

  1. Department of Biochemistry, School of Medicine, Chung Shan Medical University, Taichung, Taiwan, China

    Yi-Hsien Hsieh

  2. Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan, China

    Yi-Hsien Hsieh

  3. Terry Fox Cancer Research Laboratory, China Medical University Hospital, 2 Yuh-Der Road, Taichung, 404, Taiwan, China

    Wen-Shin Chang, Chia-Wen Tsai, Chin-Mu Hsu, Long-Bin Jeng & Da-Tian Bau

  4. Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, China

    Wen-Shin Chang & Da-Tian Bau

  5. Department of Nephrology, Buddhist Dalin Tzu Chi General Hospital, Chiayi, Taiwan

    Jen-Pi Tsai

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  1. Yi-Hsien Hsieh
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Correspondence to Da-Tian Bau.

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Yi-Hsien Hsieh and Wen-Shin Chang contributed equally to this work.

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Hsieh, YH., Chang, WS., Tsai, CW. et al. DNA double-strand break repair gene XRCC7 genotypes were associated with hepatocellular carcinoma risk in Taiwanese males and alcohol drinkers. Tumor Biol. 36, 4101–4106 (2015). https://doi.org/10.1007/s13277-014-2934-5

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  • DOI: https://doi.org/10.1007/s13277-014-2934-5

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