Tumor Biology

, Volume 35, Issue 1, pp 689–694 | Cite as

Quantitative assessment of the influence of common variations on 6p21 and lung cancer risk

  • Jicheng TanTai
  • Yuzhou Shen
  • Heng Zhao
Research Article


Genome-wide association studies have identified 6p21 as a new lung cancer susceptibility locus in populations of European descent. Since then, the relationship between common variations on 6p21 and lung cancer has been reported in various ethnic groups; however, these studies have yielded inconsistent results. To investigate this inconsistency, we performed a meta-analysis of 11 studies involving a total of 36,890 cases and 52,767 controls for three widely studies polymorphisms (rs4324798, rs3117582, and rs9295740) to evaluate its effect on genetic susceptibility for lung cancer. An overall random-effects per-allele odds ratio (OR) of 1.11 (95 % confidence interval (CI) 1.04–1.19; P = 0.002) and 1.20 (95 % CI 1.14–1.26; P < 10−5) was found for the rs4324798 and rs3117582 polymorphism, respectively. Marginal significant associations were also detected for rs9295740 with per-allele OR of 1.09 (95 % CI 1.01–1.18; P = 0.03). In the subgroup analysis by ethnicity, significantly increased risks were found for the three polymorphisms among Caucasians. Similar results were also observed using dominant or recessive genetic models. This meta-analysis demonstrated that the three common variations (rs4324798, rs3117582, and rs9295740) on 6p21 are risk factors associated with increased lung cancer susceptibility, but these associations vary in different ethnic populations.


6p21 Polymorphism Lung cancer Meta-analysis 


Conflicts of interest


Supplementary material

13277_2013_1094_MOESM1_ESM.doc (116 kb)
ESM 1 (DOC 116 kb).


  1. 1.
    Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009;59:225–49.PubMedCrossRefGoogle Scholar
  2. 2.
    Cote ML, Chen W, Smith DW, Benhamou S, Bouchardy C, Butkiewicz D, et al. Meta- and pooled analysis of GSTP1 polymorphism and lung cancer: a HuGE-GSEC review. Am J Epidemiol. 2009;169:802–14.PubMedCrossRefGoogle Scholar
  3. 3.
    Schabath MB, Spitz MR, Hong WK, Delclos GL, Reynolds WF, Gunn GB, et al. A myeloperoxidase polymorphism associated with reduced risk of lung cancer. Lung Cancer. 2002;37:35–40.PubMedCrossRefGoogle Scholar
  4. 4.
    Kiyohara C, Yoshimasu K, Shirakawa T, Hopkin JM. Genetic polymorphisms and environmental risk of lung cancer: a review. Rev Environ Health. 2004;19:15–38.PubMedCrossRefGoogle Scholar
  5. 5.
    McKay JD, Hung RJ, Gaborieau V, Boffetta P, Chabrier A, Byrnes G, et al. Lung cancer susceptibility locus at 5p15.33. Nat Genet. 2008;40:1404–6.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Rafnar T, Sulem P, Stacey SN, Geller F, Gudmundsson J, Sigurdsson A, et al. Sequence variants at the TERT-CLPTM1L locus associate with many cancer types. Nat Genet. 2009;41:221–7.PubMedCrossRefGoogle Scholar
  7. 7.
    Hu Z, Wu C, Shi Y, Guo H, Zhao X, Yin Z, et al. A genome-wide association study identifies two new lung cancer susceptibility loci at 13q12.12 and 22q12.2 in Han Chinese. Nat Genet. 2011;43:792–6.PubMedCrossRefGoogle Scholar
  8. 8.
    Lan Q, Hsiung CA, Matsuo K, Hong YC, Seow A, Wang Z, et al. Genome-wide association analysis identifies new lung cancer susceptibility loci in never-smoking women in Asia. Nat Genet. 2012;44:1330–5.PubMedCrossRefGoogle Scholar
  9. 9.
    Wang Y, Broderick P, Webb E, Wu X, Vijayakrishnan J, Matakidou A, et al. Common 5p15.33 and 6p21.33 variants influence lung cancer risk. Nat Genet. 2008;40:1407–9.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Broderick P, Wang Y, Vijayakrishnan J, Matakidou A, Spitz MR, Eisen T, et al. Deciphering the impact of common genetic variation on lung cancer risk: a genome-wide association study. Cancer Res. 2009;69:6633–41.PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Hung RJ, McKay JD, Gaborieau V, Boffetta P, Hashibe M, Zaridze D, et al. A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25. Nature. 2008;452:633–7.PubMedCrossRefGoogle Scholar
  12. 12.
    Truong T, Hung RJ, Amos CI, Wu X, Bickeboller H, Rosenberger A, et al. Replication of lung cancer susceptibility loci at chromosomes 15q25, 5p15, and 6p21: a pooled analysis from the International Lung Cancer Consortium. J Natl Cancer Inst. 2010;102:959–71.PubMedCrossRefGoogle Scholar
  13. 13.
    Zhang M, Hu L, Shen H, Dong J, Shu Y, Xu L, et al. Candidate variants at 6p21.33 and 6p22.1 and risk of non-small cell lung cancer in a Chinese population. Int J Mol Epidemiol Genet. 2010;1:11–8.PubMedCentralPubMedGoogle Scholar
  14. 14.
    Li DW, Collier DA, He L. Meta-analysis shows strong positive association of the neuregulin 1 (NRG1) gene with schizophrenia. Hum Mol Genet. 2006;15:1995–2002.PubMedCrossRefGoogle Scholar
  15. 15.
    Wang H, Yang Z, Zhang H. Assessing interactions between the associations of fibroblast growth factor receptor 2 common genetic variants and hormone receptor status with breast cancer risk. Breast Cancer Res Treat. 2013;137:511–22.PubMedCrossRefGoogle Scholar
  16. 16.
    Woolf B. On estimating the relation between blood group and disease. Ann Hum Genet. 1955;19:251–3.PubMedCrossRefGoogle Scholar
  17. 17.
    Cochran WG. The combination of estimates from different experiments. Biometrics. 1954;10:101–29.CrossRefGoogle Scholar
  18. 18.
    Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60.PubMedCrossRefGoogle Scholar
  19. 19.
    Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22:719–48.PubMedGoogle Scholar
  20. 20.
    DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.PubMedCrossRefGoogle Scholar
  21. 21.
    Egger M, Davey Smith G, Schneider M. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34.PubMedCrossRefGoogle Scholar
  22. 22.
    Zienolddiny S, Skaug V, Landvik NE, Ryberg D, Phillips DH, Houlston R, et al. The TERT-CLPTM1L lung cancer susceptibility variant associates with higher DNA adduct formation in the lung. Carcinogenesis. 2009;30:1368–71.PubMedCrossRefGoogle Scholar
  23. 23.
    Landi MT, Chatterjee N, Yu K, Goldin LR, Goldstein AM, Rotunno M, et al. A genome-wide association study of lung cancer identifies a region of chromosome 5p15 associated with risk for adenocarcinoma. Am J Hum Genet. 2009;85:679–91.PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Miki D, Kubo M, Takahashi A, Yoon KA, Kim J, Lee GK, et al. Variation in TP63 is associated with lung adenocarcinoma susceptibility in Japanese and Korean populations. Nat Genet. 2010;42:893–6.PubMedCrossRefGoogle Scholar
  25. 25.
    Wang Y, Broderick P, Matakidou A, Eisen T, Houlston RS. Role of 5p15.33 (TERT-CLPTM1L), 6p21.33 and 15q25.1 (CHRNA5-CHRNA3) variation and lung cancer risk in never-smokers. Carcinogenesis. 2010;31:234–8.PubMedCrossRefGoogle Scholar
  26. 26.
    Jaworowska E, Trubicka J, Lener MR, Masojć B, Złowocka-Perłowska E, McKay JD, et al. Smoking related cancers and loci at chromosomes 15q25, 5p15, 6p22.1 and 6p21.33 in the Polish population. PLoS One. 2011;6:e25057.PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Shiraishi K, Kunitoh H, Daigo Y, Takahashi A, Goto K, Sakamoto H, et al. A genome-wide association study identifies two new susceptibility loci for lung adenocarcinoma in the Japanese population. Nat Genet. 2012;44:900–3.PubMedCrossRefGoogle Scholar
  28. 28.
    Bae EY, Lee SY, Kang BK, Lee EJ, Choi YY, Kang HG, et al. Replication of results of genome-wide association studies on lung cancer susceptibility loci in a Korean population. Respirology. 2012;17:699–706.PubMedCrossRefGoogle Scholar
  29. 29.
    Hecht SS. Cigarette smoking and lung cancer: chemical mechanisms and approaches to prevention. Lancet Oncol. 2002;3:461–9.PubMedCrossRefGoogle Scholar
  30. 30.
    Lohmueller KE, Pearce CL, Pike M, Lander ES, Hirschhorn JN. Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease. Nat Genet. 2003;33:177–82.PubMedCrossRefGoogle Scholar
  31. 31.
    Vineis P, Alavanja M, Buffler P, Fontham E, Franceschi S, Gao YT, et al. Tobacco and cancer: recent epidemiological evidence. J Natl Cancer Inst. 2004;96:99–106.PubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  1. 1.Department of Thoracic SurgeryShanghai Chest Hospital affiliated to Shanghai Jiao Tong UniversityShanghaiPeople’s Republic of China

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