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XPC gene polymorphisms contribute to bladder cancer susceptibility: a meta-analysis

  • Research Article
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Tumor Biology

Abstract

Numerous studies have investigated the association between three polymorphisms (Lys939Gln, Ala499Val and PAT−/+) of Xeroderma pigmentosum group C (XPC) gene and bladder cancer susceptibility; however, the findings are inconclusive. In order to acquire a more precise estimation of the relationship, we performed a meta-analysis based on 10 studies including 3,934 cases and 4,269 controls for Lys939Gln, five studies including 2,113 cases and 2,249 controls for Ala499Val, and seven studies including 2,834 cases and 3,048 controls for PAT−/+ polymorphism. We searched publications from EMBASE, MEDLINE, and Chinese Biomedical. We calculated pooled odds ratio (OR) and 95 % confidence interval (CI) by using either fixed-effects or random-effects model according to the between-study heterogeneity. We found that all studied polymorphisms were individually associated with increased overall cancer risks, as shown by ORs (95 % CIs) below: the Lys939Gln (Gln/Gln vs. Lys/Lys: OR = 1.39, 95 % CI = 1.08–1.79; recessive model: OR = 1.42, 95 % CI = 1.11–1.83; and allele comparing: OR = 1.12, 95 % CI = 1.003–1.24), the Ala499Val (Val/Val vs. Ala/Ala: OR = 1.82, 95 % CI = 1.19–2.79; recessive model: OR = 1.70, 95 % CI = 1.18–2.46; and allele comparing: OR = 1.23, 95 % CI = 1.01–1.50), and the PAT−/+ (+/+ vs. −/−: OR = 1.36, 95 % CI = 1.03–1.79 and recessive model: OR = 1.34, 95 % CI = 1.06–1.70). Furthermore, stratification analyses demonstrated an increased risk for Asian populations as to the Lys939Gln and PAT−/+ whereas for Caucasian populations as to the Ala499Val polymorphism in the homozygous and recessive models. Despite some limitations, this meta-analysis suggests that XPC polymorphisms are associated with bladder cancer risk, but this association warrants further validation in well-designed studies with large sample sizes.

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Abbreviations

NER:

Nucleotide excision repair

SNP:

Single nucleotide polymorphism

DRC:

DNA repair capacity

XPC:

Xeroderma pigmentosum complementation group C

CBM:

Chinese Biomedical

OR:

Odds ratio

CI:

Confidence interval

HWE:

Hardy–Weinberg equilibrium.

References

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, et al. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.

    Article  PubMed  Google Scholar 

  2. Parkin DM. The global health burden of infection-associated cancers in the year 2002. Int J Cancer. 2006;118:3030–44.

    Article  CAS  PubMed  Google Scholar 

  3. Friedberg EC. How nucleotide excision repair protects against cancer. Nat Rev Cancer. 2001;1:22–33.

    Article  CAS  PubMed  Google Scholar 

  4. De Silva IU, McHugh PJ, Clingen PH, Hartley JA. Defining the roles of nucleotide excision repair and recombination in the repair of DNA interstrand cross-links in mammalian cells. Mol Cell Biol. 2000;20:7980–90.

    Article  PubMed Central  PubMed  Google Scholar 

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

    CAS  Google Scholar 

  6. Sugasawa K, Ng JM, Masutani C, Iwai S, van der Spek PJ, et al. Xeroderma pigmentosum group C protein complex is the initiator of global genome nucleotide excision repair. Mol Cell. 1998;2:223–32.

    Article  CAS  PubMed  Google Scholar 

  7. Thoma BS, Vasquez KM. Critical DNA damage recognition functions of XPC-hHR23B and XPA-RPA in nucleotide excision repair. Mol Carcinog. 2003;38:1–13.

    Article  CAS  PubMed  Google Scholar 

  8. Wood RD. DNA damage recognition during nucleotide excision repair in mammalian cells. Biochimie. 1999;81:39–44.

    Article  CAS  PubMed  Google Scholar 

  9. Rouissi K, Ouerhani S, Hamrita B, Bougatef K, Marrakchi R, et al. Smoking and polymorphisms in xenobiotic metabolism and DNA repair genes are additive risk factors affecting bladder cancer in Northern Tunisia. Pathol Oncol Res. 2011;17:879–86.

    Article  CAS  PubMed  Google Scholar 

  10. Garcia-Closas M, Malats N, Real FX, Welch R, Kogevinas M, et al. Genetic variation in the nucleotide excision repair pathway and bladder cancer risk. Cancer Epidemiol Biomarkers Prev. 2006;15:536–42.

    Article  CAS  PubMed  Google Scholar 

  11. Sak SC, Barrett JH, Paul AB, Bishop DT, Kiltie AE. The polyAT, intronic IVS11-6 and Lys939Gln XPC polymorphisms are not associated with transitional cell carcinoma of the bladder. Br J Cancer. 2005;92:2262–5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Wu X, Gu J, Grossman HB, Amos CI, Etzel C, et al. Bladder cancer predisposition: a multigenic approach to DNA-repair and cell-cycle-control genes. Am J Hum Genet. 2006;78:464–79.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Fontana L, Bosviel R, Delort L, Guy L, Chalabi N, et al. DNA repair gene ERCC2, XPC, XRCC1, XRCC3 polymorphisms and associations with bladder cancer risk in a French cohort. Anticancer Res. 2008;28:1853–6.

    CAS  PubMed  Google Scholar 

  14. de Verdier PJ, Sanyal S, Bermejo JL, Steineck G, Hemminki K, et al. Genotypes, haplotypes and diplotypes of three XPC polymorphisms in urinary-bladder cancer patients. Mutat Res. 2010;694:39–44.

    Article  PubMed  Google Scholar 

  15. Gangwar R, Mandhani A, Mittal RD. XPC gene variants: a risk factor for recurrence of urothelial bladder carcinoma in patients on BCG immunotherapy. J Cancer Res Clin Oncol. 2010;136:779–86.

    Article  PubMed  Google Scholar 

  16. Rouissi K, Bahria IB, Bougatef K, Marrakchi R, Stambouli N, et al. The effect of tobacco, XPC, ERCC2 and ERCC5 genetic variants in bladder cancer development. BMC Cancer. 2011;11:101.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Mittal RD, Mandal RK. Genetic variation in nucleotide excision repair pathway genes influence prostate and bladder cancer susceptibility in North Indian population. Indian J Hum Genet. 2012;18:47–55.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Liu Y, Wang H, Lin T, Wei Q, Zhi Y, et al. Interactions between cigarette smoking and XPC-PAT genetic polymorphism enhance bladder cancer risk. Oncol Rep. 2012;28:337–45.

    CAS  PubMed  Google Scholar 

  19. Wen H, Ding Q, Fang ZJ, Xia GW, Fang J. Population study of genetic polymorphisms and superficial bladder cancer risk in Han-Chinese smokers in Shanghai. Int Urol Nephrol. 2009;41:855–64.

    Article  PubMed  Google Scholar 

  20. Sanyal S, Festa F, Sakano S, Zhang Z, Steineck G, et al. Polymorphisms in DNA repair and metabolic genes in bladder cancer. Carcinogenesis. 2004;25:729–34.

    Article  CAS  PubMed  Google Scholar 

  21. Zhu Y, Lai M, Yang H, Lin J, Huang M, et al. Genotypes, haplotypes and diplotypes of XPC and risk of bladder cancer. Carcinogenesis. 2007;28:698–703.

    Article  CAS  PubMed  Google Scholar 

  22. Zhi Y, Yu J, Liu Y, Wei Q, Yuan F, et al. Interaction between polymorphisms of DNA repair genes significantly modulated bladder cancer risk. Int J Med Sci. 2012;9:498–505.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Stern MC, Lin J, Figueroa JD, Kelsey KT, Kiltie AE, et al. Polymorphisms in DNA repair genes, smoking, and bladder cancer risk: findings from the international consortium of bladder cancer. Cancer Res. 2009;69:6857–64.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Broberg K, Bjork J, Paulsson K, Hoglund M, Albin M. Constitutional short telomeres are strong genetic susceptibility markers for bladder cancer. Carcinogenesis. 2005;26:1263–71.

    Article  CAS  PubMed  Google Scholar 

  25. Sak SC, Barrett JH, Paul AB, Bishop DT, Kiltie AE. Comprehensive analysis of 22 XPC polymorphisms and bladder cancer risk. Canc Epi Bio Prev. 2006;15:2537–41.

    Article  CAS  Google Scholar 

  26. Andrew AS, Nelson HH, Kelsey KT, Moore JH, Meng AC, et al. Concordance of multiple analytical approaches demonstrates a complex relationship between DNA repair gene SNPs, smoking and bladder cancer susceptibility. Carcinogenesis. 2006;27:1030–7.

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  29. 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  CAS  PubMed  Google Scholar 

  30. Qiu L, Wang Z, Shi X. Associations between XPC polymorphisms and risk of cancers: a meta-analysis. Eur J Cancer. 2008;44:2241–53.

    Article  CAS  PubMed  Google Scholar 

  31. Zhang D, Chen C, Fu X, Gu S, Mao Y, et al. A meta-analysis of DNA repair gene XPC polymorphisms and cancer risk. J Hum Genet. 2008;53:18–33.

    Article  CAS  PubMed  Google Scholar 

  32. Francisco G, Menezes PR, Eluf-Neto J, Chammas R. XPC polymorphisms play a role in tissue-specific carcinogenesis: a meta-analysis. Eur J Hum Genet. 2008;16:724–34.

    Article  CAS  PubMed  Google Scholar 

  33. Shen MR, Jones IM, Mohrenweiser H. Nonconservative amino acid substitution variants exist at polymorphic frequency in DNA repair genes in healthy humans. Cancer Res. 1998;58:604–8.

    CAS  PubMed  Google Scholar 

  34. Khan SG, Metter EJ, Tarone RE, Bohr VA, Grossman L, et al. A new xeroderma pigmentosum group C poly(AT) insertion/deletion polymorphism. Carcinogenesis. 2000;21:1821–5.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Jin-Hong Zhu for providing help in revision and modification of this paper. This work was supported by National Natural Science Foundation of China Grant 81101506.

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Authors and Affiliations

  1. Department of Oncology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, People’s Republic of China

    Qiang-Sheng Dai, Rui-Xi Hua, Rui-Fang Zeng, Jian-Ting Long & Zhen-Wei Peng

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  1. Qiang-Sheng Dai
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  2. Rui-Xi Hua
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Correspondence to Qiang-Sheng Dai.

Additional information

Qiang-Sheng Dai and Rui-Xi Hua contributed equally to this study and should be considered as co-first authors.

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Dai, QS., Hua, RX., Zeng, RF. et al. XPC gene polymorphisms contribute to bladder cancer susceptibility: a meta-analysis. Tumor Biol. 35, 447–453 (2014). https://doi.org/10.1007/s13277-013-1062-y

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  • DOI: https://doi.org/10.1007/s13277-013-1062-y

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