Skip to main content

Advertisement

Log in

Polymorphisms of the XPC gene may contribute to the risk of head and neck cancer: a meta-analysis

  • Research Article
  • Published:
Tumor Biology

Abstract

Polymorphisms of the XPC gene have been reported to be associated with an increased risk of head and neck cancer (HNC), though the exact biological effect is still unclear. Genetic association studies (GAS) investigating the associations between three common polymorphisms (PAT, Lys939Gln, and Ala499Val) of the XPC gene and HNC risk have produced contradictory and inconclusive results. The aim of this meta-analysis is to evaluate the contributions of these polymorphisms to the risk of HNC. A literature search was conducted in the PubMed, Embase, Web of Science, Cochrane Library, and China National Knowledge Infrastructure databases to indentify eligible studies. Pooled odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were used to evaluate the strength of the associations under a fixed- or random-effect model according to heterogeneity test. Twelve case-control studies were included in this meta-analysis with a total of 3,078 HNC patients and 4,311 healthy controls. For XPC PAT, a significant overall association was found under all major genetic models. Stratified analyses further indicated significant associations in the Caucasian, population-based, non-PCR-RFLP, esophageal cancer and oral cancer subgroups. For XPC Lys939Gln, few significant results were found in either the overall analysis or stratified analyses. For XPC Ala499Val, the combined results revealed a significantly increased risk of HNC for carriers of the 499Val allele. This meta-analysis shows that the XPC PAT and Ala499Val polymorphisms may be associated with an increased risk of HNC, while XPC Lys939Gln may not be associated with HNC risk. Despite some limitations, this meta-analysis establishes solid statistical evidence for an association between XPC genetic polymorphisms and HNC risk that warrants further validation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

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. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62:10–29.

    Article  PubMed  Google Scholar 

  3. Rose BS, Jeong JH, Nath SK, Lu SM, Mell LK. Population-based study of competing mortality in head and neck cancer. J Clin Oncol. 2011;29:3503–9.

    Article  PubMed  Google Scholar 

  4. Argiris A, Karamouzis MV, Raben D, Ferris RL. Head and neck cancer. Lancet. 2008;371:1695–709.

    Article  CAS  PubMed  Google Scholar 

  5. Marur S, D'Souza G, Westra WH, Forastiere AA. Hpv-associated head and neck cancer: a virus-related cancer epidemic. Lancet Oncol. 2010;11:781–9.

    Article  PubMed  Google Scholar 

  6. Marron M, Boffetta P, Zhang ZF, Zaridze D, Wunsch-Filho V, et al. Cessation of alcohol drinking, tobacco smoking and the reversal of head and neck cancer risk. Int J Epidemiol. 2010;39:182–96.

    Article  PubMed Central  PubMed  Google Scholar 

  7. Leemans CR, Braakhuis BJ, Brakenhoff RH. The molecular biology of head and neck cancer. Nat Rev Cancer. 2011;11:9–22.

    Article  CAS  PubMed  Google Scholar 

  8. Clement FC, Camenisch U, Fei J, Kaczmarek N, Mathieu N, et al. Dynamic two-stage mechanism of versatile DNA damage recognition by xeroderma pigmentosum group C protein. Mutat Res. 2010;685:21–8.

    Article  CAS  PubMed  Google Scholar 

  9. Shell SM, Hawkins EK, Tsai MS, Hlaing AS, Rizzo CJ, et al. Xeroderma pigmentosum complementation group c protein (XPC) serves as a general sensor of damaged DNA. DNA Repair. 2013;12:947–53.

    Article  CAS  PubMed  Google Scholar 

  10. Bergink S, Toussaint W, Luijsterburg MS, Dinant C, Alekseev S, et al. Recognition of DNA damage by XPC coincides with disruption of the xpc-rad23 complex. J Cell Biol. 2012;196:681–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Pascucci B, D'Errico M, Parlanti E, Giovannini S, Dogliotti E. Role of nucleotide excision repair proteins in oxidative DNA damage repair: an updating. Biochemistry. 2011;76:4–15.

    CAS  PubMed  Google Scholar 

  12. Shen H, Sturgis EM, Khan SG, Qiao Y, Shahlavi T, et al. An intronic poly (at) polymorphism of the DNA repair gene XPC and risk of squamous cell carcinoma of the head and neck: a case–control study. Cancer Res. 2001;61:3321–5.

    CAS  PubMed  Google Scholar 

  13. Casson AG, Zheng Z, Evans SC, Veugelers PJ, Porter GA, et al. Polymorphisms in DNA repair genes in the molecular pathogenesis of esophageal (Barrett) adenocarcinoma. Carcinogenesis. 2005;26:1536–41.

    Article  CAS  PubMed  Google Scholar 

  14. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the prisma statement. BMJ. 2009;339:b2535.

    Article  PubMed Central  PubMed  Google Scholar 

  15. Little J, Higgins JP, Ioannidis JP, Moher D, Gagnon F, et al. Strengthening the reporting of genetic association studies (STREGA): an extension of the strobe statement. Hum Genet. 2009;125:131–51.

    Article  PubMed  Google Scholar 

  16. Stang A. Critical evaluation of the newcastle-ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25:603–5.

    Article  PubMed  Google Scholar 

  17. Jackson D, White IR, Riley RD. Quantifying the impact of between-study heterogeneity in multivariate meta-analyses. Stat Med. 2012;31:3805–20.

    Article  PubMed Central  PubMed  Google Scholar 

  18. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–58.

    Article  PubMed  Google Scholar 

  19. Sacks HS, Berrier J, Reitman D, Ancona-Berk VA, Chalmers TC. Meta-analyses of randomized controlled trials. N Engl J Med. 1987;316:450–5.

    Article  CAS  PubMed  Google Scholar 

  20. Peters JL, Sutton AJ, Jones DR, Abrams KR, Rushton L. Comparison of two methods to detect publication bias in meta-analysis. JAMA. 2006;295:676–80.

    Article  CAS  PubMed  Google Scholar 

  21. 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 Central  PubMed  Google Scholar 

  22. Abbasi R, Ramroth H, Becher H, Dietz A, Schmezer P, et al. Laryngeal cancer risk associated with smoking and alcohol consumption is modified by genetic polymorphisms in ERCC5, ERCC 6 and RAD23B but not by polymorphisms in five other nucleotide excision repair genes. Int J Cancer. 2009;125:1431–9.

    Article  CAS  PubMed  Google Scholar 

  23. An J, Liu Z, Hu Z, Li G, Wang LE, et al. Potentially functional single nucleotide polymorphisms in the core nucleotide excision repair genes and risk of squamous cell carcinoma of the head and neck. Cancer Epidemiol Biomarkers Prev. 2007;16:1633–8.

    Article  CAS  PubMed  Google Scholar 

  24. Guo W, Zhou RM, Wan LL, Wang N, Li Y, et al. Polymorphisms of the DNA repair gene xeroderma pigmentosum groups A and C and risk of esophageal squamous cell carcinoma in a population of high incidence region of north china. J Cancer Res Clin Oncol. 2008;134:263–70.

    Article  CAS  PubMed  Google Scholar 

  25. Kietthubthew S, Sriplung H, Au WW, Ishida T. Polymorphism in DNA repair genes and oral squamous cell carcinoma in thailand. Int J Hyg Environ Health. 2006;209:21–9.

    Article  CAS  PubMed  Google Scholar 

  26. Pan J, Lin J, Izzo JG, Liu Y, Xing J, et al. Genetic susceptibility to esophageal cancer: the role of the nucleotide excision repair pathway. Carcinogenesis. 2009;30:785–92.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Sugimura T, Kumimoto H, Tohnai I, Fukui T, Matsuo K, et al. Gene–environment interaction involved in oral carcinogenesis: molecular epidemiological study for metabolic and DNA repair gene polymorphisms. J Oral Pathol Med. 2006;35:11–8.

    Article  CAS  PubMed  Google Scholar 

  28. Yang M, Kang MJ, Choi Y, Kim CS, Lee SM, et al. Associations between XPC expression, genotype, and the risk of head and neck cancer. Environ Mol Mutagen. 2005;45:374–9.

    Article  CAS  PubMed  Google Scholar 

  29. Yang ZH, Liang WB, Jia J, Wei YS, Zhou B, et al. The xeroderma pigmentosum group C gene polymorphisms and genetic susceptibility of nasopharyngeal carcinoma. Acta Oncol (Stockholm, Sweden). 2008;47:379–84.

    Article  CAS  Google Scholar 

  30. Ye W, Kumar R, Bacova G, Lagergren J, Hemminki K, et al. The XPD 751Gln allele is associated with an increased risk for esophageal adenocarcinoma: a population-based case–control study in sweden. Carcinogenesis. 2006;27:1835–41.

    Article  CAS  PubMed  Google Scholar 

  31. Zhu XL. Study on relationship between DNA repair genes polymorphism of HOGG1, XPC, XPA and esophageal squamous cell carcinoma susceptibility. Huazhong University of Science and Technology, 2008.

  32. Ricceri F, Matullo G, Vineis P. Is there evidence of involvement of DNA repair polymorphisms in human cancer? Mutat Res. 2012;736:117–21.

    Article  CAS  PubMed  Google Scholar 

  33. Jalal S, Earley JN, Turchi JJ. DNA repair: from genome maintenance to biomarker and therapeutic target. Clin Cancer Res. 2011;17:6973–84.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Misteli T, Soutoglou E. The emerging role of nuclear architecture in DNA repair and genome maintenance. Nat Rev Mol Cell Biol. 2009;10:243–54.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Warmerdam DO, Kanaar R. Dealing with DNA damage: relationships between checkpoint and repair pathways. Mutat Res. 2010;704:2–11.

    Article  CAS  PubMed  Google Scholar 

  36. Legerski RJ, Liu P, Li L, Peterson CA, Zhao Y, et al. Assignment of xeroderma pigmentosum group C (XPC) gene to chromosome 3p25. Genomics. 1994;21:266–9.

    Article  CAS  PubMed  Google Scholar 

  37. 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 

  38. Munafo MR, Flint J. Meta-analysis of genetic association studies. Trends Genet. 2004;20:439–44.

    Article  CAS  PubMed  Google Scholar 

  39. Dai QS, Hua RX, Zeng RF, Long JT, Peng ZW. XPC gene polymorphisms contribute to bladder cancer susceptibility: a meta-analysis. Tumour Biol. 2013. doi:10.1007/s13277-013-1062-y.

  40. Dou K, Xu Q, Han X. The association between XPC Lys939Gln gene polymorphism and urinary bladder cancer susceptibility: a systematic review and meta-analysis. Diagn Pathol. 2013;8:112.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Zhang Y, Wang X, Zhang W, Gong S. An association between XPC Lys939Gln polymorphism and the risk of bladder cancer: a meta-analysis. Tumour Biol. 2013;34:973–82.

    Article  CAS  PubMed  Google Scholar 

  42. Liu C, Yin Q, Hu J, Li L, Zhang Y, et al. A meta-analysis of evidences on XPC polymorphisms and lung cancer susceptibility. Tumour Biol. 2013;34:1205–13.

    Article  CAS  PubMed  Google Scholar 

  43. Ji G, Lin Y, Cao SY, Li LZ, Chen XL, et al. XPC 939A>C and 499C>T polymorphisms and skin cancer risk: a meta-analysis. Asian Pac J Cancer Prev. 2012;13:4983–8.

    Article  PubMed  Google Scholar 

  44. Wang F, Zou YF, Sun GP. Xpc gene polymorphisms and breast cancer susceptibility: appraisal of a recent meta-analysis. Breast Cancer Res Treat. 2011;129:277–9.

    Article  PubMed  Google Scholar 

  45. Zheng W, Cong XF, Cai WH, Yang S, Mao C, et al. Current evidences on XPC polymorphisms and breast cancer susceptibility: a meta-analysis. Breast Cancer Res Treat. 2011;128:811–5.

    Article  PubMed  Google Scholar 

  46. Dai QS, Hua RX, Zhang R, Huang YS, Hua ZM, et al. Poly (at) deletion/insertion polymorphism of the xpc gene contributes to urinary system cancer susceptibility: a meta-analysis. Gene. 2013;528:335–42.

    Article  CAS  PubMed  Google Scholar 

  47. Jiang X, Zhou LT, Zhang SC, Chen K. XPC polymorphism increases risk of digestive system cancers: current evidence from a meta-analysis. Chin J Cancer Res. 2012;24:181–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgment

This work was supported by the grants from the National Natural Science Foundation of China (Nos. 81302374, 81241084), Beijing Natural Science Foundation (Nos. 7121005, 5122016), and Beijing Nova Program (No. 2013043).

Conflicts of interest

None

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Zhigang Huang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, Y., Li, Z., Zhong, Q. et al. Polymorphisms of the XPC gene may contribute to the risk of head and neck cancer: a meta-analysis. Tumor Biol. 35, 3917–3931 (2014). https://doi.org/10.1007/s13277-013-1520-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-013-1520-6

Keywords

Navigation