Skip to main content
SpringerLink
Log in

Association of ERCC2/XPD polymorphisms and interaction with tobacco smoking in lung cancer susceptibility: a systemic review and meta-analysis

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

    We’re sorry, something doesn't seem to be working properly.

    Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Abstract

The association of the two ERCC polymorphisms, Asp312Asn and Lys751Gln, with lung cancer risk remains controversial and inconclusive. To better evaluate the potential role of the two polymorphisms and interaction with tobacco smoking in lung cancer susceptibility presented in diverse populations, we have conducted a meta-analysis based on 26 studies from 24 publications which included analyses of Asp312Asn (7121 cases, 8962 controls) and Lys751Gln (8396 cases, 10510 controls) polymorphisms. Overall, significantly elevated lung cancer risk was associated with ERCC2 312Asn allele(homozygous model: OR = 1.20[1.05–1.36], P = 0.006; recessive model: OR = 1.20[1.06–1.35], P = 0.004) and 751Gln allele(homozygous model: OR = 1.31[1.17–1.46], P < 0.00001; heterozygous model: OR = 1.11[1.04–1.19], P = 0.003; recessive model: OR = 1.23[1.11–1.37], P < 0.0001; dominant model: OR = 1.15[1.08–1.23], P < 0.0001). In ethnic subgroup analyses, significantly increased risk was associated with ERCC2 312Asn allele for both Caucasians and Asians, and 751Gln allele for both Caucasians and Latino-Americans. When stratified by smoking status, significantly elevated risk of both polymorphisms for never-smokers was detected (dominant model, OR = 1.46[1.09–1.95] and 1.57[1.19–2.08], P = 0.01 and 0.002, respectively). In conclusion, this meta-analysis suggests that the two ERCC2 polymorphisms may contribute to lung cancer susceptibility serving as low-penetrance risk factors. Extremely large-scale evidence would be necessary to confirm the effects on ethnically specific populations and gene-environment interactions.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

ERCC2:

Excision repair cross-complementing group 2

XPD:

Xeroderma pigmentosum complementary group D

HWE:

Hardy–Weinberg equilibrium

OR:

Odds ratio

CI:

Confidence Interval

BPDE:

Benzo[a] pyrene dihydrodiol epoxide

References

  1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM (2010) Estimates of worldwide burden of cancer in 2008: GOLOBCAN 2008. Int J Cancer (in press). doi:10.1002/ijc.25516

  2. Jernal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ (2009) Cancer statistics, 2009. CA Cancer J Clin 59:225–249

    Article  Google Scholar 

  3. Hecht SS (1999) Tobacco smoke carcinogens and lung cancer. J Natl Cancer Inst 91(14):1194–1210

    Article  PubMed  CAS  Google Scholar 

  4. Subramanian J, Govindan R (2007) Lung cancer in never smokers: a review. J Clin Oncol 25:561–570

    Article  PubMed  Google Scholar 

  5. Goode EL, Ulrich CM, Potter JD (2002) Polymorphisms in DNA repair genes and associations with cancer risk. Cancer Epidemiol Biomarkers Prev 11:1513–1530

    PubMed  CAS  Google Scholar 

  6. Benhamou S, Sarasin A (2005) ERCC2/XPD gene polymorphisms and lung cancer: a HuGE review. Am J Epidemiol 161:1–14

    Article  PubMed  Google Scholar 

  7. Pabalan N, Francisco-Pabalan O, Sung L, Jarjanazi H, Ozcelik H (2010) Meta-analysis of two ERCC2(XPD) polymorphisms, Asp312Asn and Lys751Gln, in breast cancer. Breast Cancer Res. Treat (in press). doi:10.1007/s10549-010-0863-6

  8. Berman NG, Parker RA (2002) Meta-analysis: neither quick nor easy. BMC Med Res Methodol 2:10

    Article  PubMed  Google Scholar 

  9. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560

    Article  PubMed  Google Scholar 

  10. DerSimonian R, Kacker R (2007) Random-effects model for meta-analysis of clinical trials: an update. Contemp Clin Trials 28:105–114

    Article  PubMed  Google Scholar 

  11. Egger M, Davey SG, Schneider M, Minder C (1977) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634

    Article  Google Scholar 

  12. Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50:1088–1101

    Article  PubMed  CAS  Google Scholar 

  13. Rohlfs RV, Weir BS (2008) Distributions of Hardy–Weinberg equilibrium test statistics. Genetics 180:1609–1616

    Article  PubMed  CAS  Google Scholar 

  14. Spitz MR, Wu X, Wang Y et al (2001) Modulation of nucleotide excision repair capacity by XPD polymorphisms in lung cancer patients. Cancer Res 61:1354–1357

    PubMed  CAS  Google Scholar 

  15. Butkiewicz D, Rusin M, Enewold L, Shields PG, Chorazy M, Harris CC (2001) Genetic polymorphisms in DNA repair genes and risk of lung cancer. Carcinogenesis 22:593–597

    Article  PubMed  CAS  Google Scholar 

  16. David-Beabes GL, Lunn RM, London SJ (2001) No association between the XPD (Lys751G1n) polymorphism or the XRCC3 (Thr241Met) polymorphism and lung cancer risk. Cancer Epidemiol Biomarkers Prev 10:911–912

    PubMed  CAS  Google Scholar 

  17. Zhou W, Liu G, Miller DP et al (2002) Gene-environment interaction for the ERCC2 polymorphisms and cumulative cigarette smoking exposure in lung cancer. Cancer Res 62:1377–1381

    PubMed  CAS  Google Scholar 

  18. Hou SM, Falt S, Angelini S et al (2002) The XPD variant alleles are associated with increased aromatic DNA adduct level and lung cancer risk. Carcinogenesis 23:599–603

    Article  PubMed  CAS  Google Scholar 

  19. Park JY, Lee SY, Jeon HS et al (2002) Lys751Gln polymorphism in the DNA repair gene XPD and risk of primary lung cancer. Lung Cancer 36:15–16

    Article  PubMed  Google Scholar 

  20. Chen S, Tang D, Xue K et al (2002) DNA repair gene XRCC1 and XPD polymorphisms and risk of lung cancer in a Chinese population. Carcinogenesis 23:1321–1325

    Article  PubMed  Google Scholar 

  21. Xing D, Tan W, Wei Q, Lin D (2002) Polymorphisms of the DNA repair gene XPD and risk of lung cancer in a Chinese population. Lung Cancer 38:123–129

    Article  PubMed  Google Scholar 

  22. Misra RR, Ratnasinghe D, Tangrea JA et al (2003) Polymorphisms in the DNA repair genes XPD, XRCC1, XRCC3, and APE/ref-1, and the risk of lung cancer among male smokers in Finland. Cancer Lett 191:171–178

    Article  PubMed  CAS  Google Scholar 

  23. Liang G, Xing D, Miao X et al (2003) Sequence variations in the DNA repair gene XPD and risk of lung cancer in a Chinese population. Int J Cancer 105:669–673

    Article  PubMed  CAS  Google Scholar 

  24. Vogel U, Laros I, Jacobsen NR et al (2004) Two regions in chromosome 19q13.2-3 are associated with risk of lung cancer. Mutat Res 546:65–74

    Article  PubMed  CAS  Google Scholar 

  25. Harms C, Salama SA, Sierra-Torres CH, Cajas-Salazar N, Au WW (2004) Polymorphisms in DNA repair genes, chromosome aberrations, and lung cancer. Environ Mol Mutagen 44:74–82

    Article  PubMed  CAS  Google Scholar 

  26. Popanda O, Schattenberg T, Phong CT et al (2004) Specific combinations of DNA repair gene variants and increased risk for non-small cell lung cancer. Carcinogenesis 25:2433–2441

    Article  PubMed  CAS  Google Scholar 

  27. Shen M, Berndt SI, Rothman N et al (2005) Polymorphisms in the DNA nucleotide excision repair genes and lung cancer risk in Xuan Wei, China. Int J Cancer 116:768–773

    Article  PubMed  CAS  Google Scholar 

  28. Zienolddiny S, Campa D, Lind H et al (2006) Polymorphisms of DNA repair genes and risk of non-small cell lung cancer. Carcinogenesis 27:560–567

    Article  PubMed  CAS  Google Scholar 

  29. Matullo G, Dunning AM, Guarrera S et al (2006) DNA repair polymorphisms and cancer risk in non-smokers in a cohort study. Carcinogenesis 27:997–1007

    Article  PubMed  CAS  Google Scholar 

  30. Hu Z, Xu L, Shao M et al (2006) Polymorphisms in the two helicases ERCC2/XPD and ERCC3/XPB of the transcription factor IIH complex and risk of lung cancer: a case-control analysis in a Chinese population. Cancer Epidemiol Biomarkers Prev 15:1336–1340

    Article  PubMed  CAS  Google Scholar 

  31. Yin J, Vogel U, Ma Y, Guo L, Wang H, Qi R (2006) Polymorphism of the DNA repair gene ERCC2 Lys751Gln and risk of lung cancer in a northeastern Chinese population. Cancer Genet Cytogenet 169:27–32

    Article  PubMed  CAS  Google Scholar 

  32. Ruyck KD, Szaumkessel M, Rudder ID et al (2007) Polymorphisms in base-excision repair and nucleotide-excision repair genes in relation to lung cancer risk. Mutat Res 631:101–110

    PubMed  Google Scholar 

  33. Lopez-Cima MF, Gonzalez-Arriaga P, Garcia-Castro L et al (2007) Polymorphisms in XPC, XPD, XRCC1, and XRCC3 DNA repair genes and lung cancer risk in a population of northern Spain. BMC Cancer 7:162

    Article  PubMed  Google Scholar 

  34. Raaschou-Nielsen O, Sørensen M, Overvad K, Tjønneland A, Vogel U (2008) Polymorphisms in nucleotide excision repair genes, smoking and intake of fruit and vegetables in relation to lung cancer. Lung cancer 59:171–179

    Article  PubMed  Google Scholar 

  35. Sreeja L, Syamala VS, Syamala V et al (2008) Prognostic importance of DNA repair gene polymorphisms of XRCC1 Arg399Gln and XPD Lys751Gln in lung cancer patients from India. J Cancer Res Clin Oncol 34:645–652

    Article  Google Scholar 

  36. Chang JS, Wrensch MR, Hansen HM et al (2008) Nucleotide excision repair genes and risk of lung cancer among San Francisco Bay Area Latinos and African Americans. Int J Cancer 123:2095–2104

    Article  PubMed  CAS  Google Scholar 

  37. Yin Z, Su M, Li X et al (2009) ERCC2, ERCC1 polymorphisms and haplotypes, cooking oil fume and lung adenocarcinoma risk in Chinese non-smoking females. J Exp Clin Cancer Res 28:153

    Article  PubMed  Google Scholar 

  38. Manuguerra M, Saletta F, Karagas MR et al (2006) XRCC3 and XPD/ERCC2 single nucleotide polymorphisms and the risk of cancer: a HuGE review. Am J Epidemiol 164:297–302

    Article  PubMed  Google Scholar 

  39. Kiyohara C, Yoshimasu K (2007) Genetic polymorphisms in the nucleotide excision repair pathway and lung cancer risk: a meta-analysis. Int J Med Sci 4:59–71

    PubMed  CAS  Google Scholar 

  40. Wang F, Chang D, Hu FL et al (2008) DNA repair gene XPD polymorphisms and cancer risk: a meta-analysis based on 56 case-control studies. Cancer Epidemiol Biomarkers Prev 17:507–517

    Article  PubMed  CAS  Google Scholar 

  41. Vineis P, Manuguerra M, Kavvoura F et al (2009) A field synopsis on low-penetrance variants in DNA repair genes and cancer susceptibility. J Natl Cancer Inst 101:24–36

    PubMed  CAS  Google Scholar 

  42. Zhang J, Qiu LX, Leaw SJ, Hu XC, Chang JH (2010) The association between XPD Asp312Asn polymorphism and lung cancer risk: a meta-analysis including 16,949 subjects. Med Oncol (in press). doi:10.1007/s12032-010-9501-8

  43. Camps C, Sirera R, Iranzo V, Tarón M, Rosell R (2007) Gene expression and polymorphisms of DNA repair enzymes: cancer susceptibility and response to chemotherapy. Clin Lung Cancer 8:369–375

    Article  PubMed  CAS  Google Scholar 

  44. Wolfe KJ, Wickliffe JK, Hill CE, Paolini M, Ammenheuser MM, Abdel-Rahman SZ (2007) Single nucleotide polymorphisms of the DNA repair gene XPD/ERCC2 alter mRNA expression. Pharmacogenet Genomics 17:897–905

    Article  PubMed  CAS  Google Scholar 

  45. Lunn RM, Helzlsouer KJ, Parshad R et al (2000) XPD polymorphisms: effects on DNA repair proficiency. Carcinogenesis 21:551–555

    Article  PubMed  CAS  Google Scholar 

  46. Qiao Y, Spitz MR, Shen H et al (2002) Modulation of repair of ultraviolet damage in the host-cell reactivation assay by polymorphic XPC and XPD/ERCC2 genotypes. Carcinogenesis 23:295–299

    Article  PubMed  CAS  Google Scholar 

  47. Au WW, Salama SA, Sierra-Torres CH (2003) Functional characterization of polymorphisms in DNA repair genes using cytogenetic challenge assays. Environ Health Perspect 111:1843–1850

    Article  PubMed  CAS  Google Scholar 

  48. Matullo G, Peluso M, Polidoro S et al (2003) Combination of DNA repair single nucleotide polymorphisms and increased levels of DNA adducts in a population-based study. Cancer Epidemiol Biomarkers Prev 12:674–677

    PubMed  CAS  Google Scholar 

  49. Zhan P, Wang Q, Wei SZ et al (2010) ERCC2/XPD Lys751Gln, Asp312Asn gene polymorphism, lung cancer risk: a meta-analysis involving 22 case-control studies. J Thorac Oncol 5(9):1337–1345

    Article  PubMed  Google Scholar 

  50. Laine JP, Mocquet V, Bonfanti M, Braun C, Egly JM, Brousset P (2007) Common XPD (ERCC2) polymorphisms have no measurable effect on nucleotide excision repair and basal transcription. DNA Repair (Amst) 6:1264–1270

    Article  CAS  Google Scholar 

  51. Zhao H, Wang LE, Li D, Chamberlain RM, Sturgis EM, Wei Q (2008) Genotypes and haplotypes of ERCC1 and ERCC2/XPD genes predict levels of benzo[a] pyrene diol epoxide-induced DNA adducts in cultured primary lymphocytes from healthy individuals: a genotype-phenotype correlation analysis. Carcinogenesis 29:1560–1566

    Article  PubMed  CAS  Google Scholar 

  52. Yin J, Vogel U, Ma Y, Qi R, Sun Z, Wang H (2007) A haplotype encompassing the variant allele of DNA repair gene polymorphism ERCC2/XPD Lys751Gln but not the variant allele of Asp312Asn is associated with risk of lung cancer in a northeastern Chinese population. Cancer Genet Cytogenet 175:47–51

    Article  PubMed  CAS  Google Scholar 

  53. Li Y, Shen CC, Ye Y et al (2010) Genetic variants and risk of lung cancer in never smokers: a genome-wide association study. Lancet Oncol 11:321–330

    Article  PubMed  CAS  Google Scholar 

  54. Landi MT, Chatterjee N, Yu K et al (2009) A genonme-wide association study of lung cancer indentifies a region of chromosome 5p15 associated with risk for adenocarcinoma. Am J Hum Genet 85:679–691

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We are indebted to Dr. Kim De Ruyck and Dr. Ole Raaschou-Nielsen for paper availability. We are grateful to Panpan Hao and Yong Zhang for expert assistant. This study was supported by the National High-Tech Research and Development Program of China (Program 863) (2007AA021802), and the Natural Science Foundation of Shandong Province of China (ZR2010HM067).

Conflicts of interest statement

None declared.

Author information

Authors and Affiliations

  1. Department of Thoracic Surgery, Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan, 250021, People’s Republic of China

    Zhen Feng, Yang Ni, Wei Dong, Hongchang Shen & Jiajun Du

Authors
  1. Zhen Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yang Ni
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wei Dong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hongchang Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jiajun Du
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jiajun Du.

Additional information

Zhen Feng and Yang Ni contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Feng, Z., Ni, Y., Dong, W. et al. Association of ERCC2/XPD polymorphisms and interaction with tobacco smoking in lung cancer susceptibility: a systemic review and meta-analysis. Mol Biol Rep 39, 57–69 (2012). https://doi.org/10.1007/s11033-011-0710-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-011-0710-9

Keywords

Search

Navigation