Molecular Biology Reports

, Volume 39, Issue 1, pp 57–69 | Cite as

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

  • Zhen Feng
  • Yang Ni
  • Wei Dong
  • Hongchang Shen
  • Jiajun Du


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.


Lung cancer ERCC2 Asp312Asn Lys751Gln Polymorphism Meta-analysis 



Excision repair cross-complementing group 2


Xeroderma pigmentosum complementary group D


Hardy–Weinberg equilibrium


Odds ratio


Confidence Interval


Benzo[a] pyrene dihydrodiol epoxide



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.


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Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Zhen Feng
    • 1
  • Yang Ni
    • 1
  • Wei Dong
    • 1
  • Hongchang Shen
    • 1
  • Jiajun Du
    • 1
  1. 1.Department of Thoracic SurgeryProvincial Hospital Affiliated to Shandong UniversityJinanPeople’s Republic of China

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