Advertisement

Tumor Biology

, Volume 36, Issue 7, pp 4987–4992 | Cite as

CHRNA3 genetic polymorphism and the risk of lung cancer in the Chinese Han smoking population

  • Wenjing Zhou
  • Tingting Geng
  • Huijuan Wang
  • Xiaojie Xun
  • Tian Feng
  • Hui Zou
  • Longli Kang
  • Tianbo Jin
  • Chao Chen
Research Article

Abstract

Lung cancer is the leading cause of cancer-related deaths worldwide that result from the combined effected of smoking exposure and genetic susceptibility. CHRNA3, a nicotinic acetylcholine receptor gene, was associated with lung cancer risk. The aim of this study was to identify whether CHRNA3 polymorphisms increase lung cancer risk directly or indirectly through smoking behavior in the Chinese Han individuals. We conducted a case–control study including 228 individuals with lung cancer and 301 healthy individuals. Seventeen known SNPs within CHRNA3 were selected for genotyping. Odds ratios (OR) and 95 % confidence interval (CI) were calculated by unconditional logistic regression with adjustment for gender and age. Two SNPs (rs8042059 and rs7177514) showed a 1.54-fold (p = 0.036; 95 % CI = 1.03–2.32) and 1.52-fold (p = 0.043; 95 % CI = 1.01–2.27) increased risk for lung cancer in smokers, respectively. Rs8042059 also showed a significant association for variant genotypes (CA/AA) compared with the wild-type genotype (CC), with an OR = 1.84 (p = 0.042; 95 % CI, 1.02–3.33) in the dominant model. In addition, the haplotype analysis found that the haplotypes “TCAC” and “CTGT,” composed of rs938682, rs12914385, rs11637630, and rs2869546, were associated with a 1.79-fold and 501-fold increased lung cancer risk, respectively. However, the polymorphisms of all SNPs were not significantly different between controls and cases among general or nonsmokers population. Rs8042059 and rs7177514 may increase lung cancer risk indirectly through smoking behavior in the Chinese Han population.

Keywords

Lung cancer Single nucleotide polymorphism (SNP) CHRNA3 Case–control study Smoking 

Notes

Acknowledgments

This work is supported by the National 863 High-Technology Research and Development Program (No. 2012AA02A519) and National Science and Technology Major Project (No. 2012ZX09506001-007). We are grateful to all patients and individuals who participated in the study. We would also like to thank clinicians and other hospital staff who helped us to collect blood samples and data.

Supplementary material

13277_2015_3149_MOESM1_ESM.doc (48 kb)
Supplementary Table S1 (DOC 48 kb)
13277_2015_3149_MOESM2_ESM.doc (43 kb)
Supplementary Table S2 (DOC 43 kb)

References

  1. 1.
    Zheng R, Zeng H, Zhang S, Fan Y, Qiao Y, Zhou Q et al. Lung cancer incidence and mortality in China, 2010. Thoracic Cancer. 2014.Google Scholar
  2. 2.
    Subramanian J, Govindan R. Lung cancer in never smokers: a review. J Clin Oncol: Off J Am Soc Clin Oncol. 2007;25(5):561–70. doi: 10.1200/jco.2006.06.8015.CrossRefGoogle Scholar
  3. 3.
    Sun S, Schiller JH, Gazdar AF. Lung cancer in never smokers—a different disease. Nat Rev Cancer. 2007;7(10):778–90. doi: 10.1038/nrc2190.CrossRefPubMedGoogle Scholar
  4. 4.
    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(5):679–91.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    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(16):6633–41.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Amos CI, Wu X, Broderick P, Gorlov IP, Gu J, Eisen T, et al. Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25. 1. Nat Genet. 2008;40(5):616–22.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Liu P, Vikis HG, Wang D, Lu Y, Wang Y, Schwartz AG, et al. Familial aggregation of common sequence variants on 15q24-25.1 in lung cancer. J Natl Cancer Inst. 2008;100(18):1326–30.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Saccone SF, Hinrichs AL, Saccone NL, Chase GA, Konvicka K, Madden PA, et al. Cholinergic nicotinic receptor genes implicated in a nicotine dependence association study targeting 348 candidate genes with 3713 SNPs. Hum Mol Genet. 2007;16(1):36–49.CrossRefPubMedGoogle Scholar
  9. 9.
    Minna JD. Nicotine exposure and bronchial epithelial cell nicotinic acetylcholine receptor expression in the pathogenesis of lung cancer. J Clin Investig. 2003;111(1):31–3.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Bierut L, Stitzel J, Wang J, Hinrichs A, Grucza R, Xuei X, et al. Variants in nicotinic receptors and risk for nicotine dependence. Am J Psychiatr. 2008;165(9):1163–71.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Schuller HM. Is cancer triggered by altered signalling of nicotinic acetylcholine receptors? Nat Rev Cancer. 2009;9(3):195–205.CrossRefPubMedGoogle Scholar
  12. 12.
    Tsurutani J, Castillo SS, Brognard J, Granville CA, Zhang C, Gills JJ, et al. Tobacco components stimulate Akt-dependent proliferation and NFkappaB-dependent survival in lung cancer cells. Carcinogenesis. 2005;26(7):1182–95. doi: 10.1093/carcin/bgi072.CrossRefPubMedGoogle Scholar
  13. 13.
    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(7187):633–7.CrossRefPubMedGoogle Scholar
  14. 14.
    Ren JH, Jin M, He WS, Liu CW, Jiang S, Chen WH, Yang KY, Wu G, Zhang T: Association between chrna3 rs1051730 genotype and lung cancer risk in Chinese Han population: a case-control study. Journal of Huazhong University of Science and Technology Medical sciences = Hua zhong ke ji da xue xue bao Yi xue Ying De wen ban = Huazhong keji daxue xuebao Yixue Yingdewen ban 2013;33:897-901.Google Scholar
  15. 15.
    Sakoda LC, Loomis MM, Doherty JA, Neuhouser ML, Barnett MJ, Thornquist MD, et al. Chromosome 15q24-25.1 variants, diet, and lung cancer susceptibility in cigarette smokers. Cancer Causes Control. 2011;22(3):449–61.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Amos CI, Gorlov IP, Dong Q, Wu X, Zhang H, Lu EY, et al. nicotinic acetylcholine receptor region on chromosome 15q25 and lung cancer risk among African Americans: a case–control study. J Natl Cancer Inst. 2010;102(15)):1199–205.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Truong T, Hung RJ, Amos CI, Wu X, Bickeböller 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(13):959–71.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Gabriel S, Ziaugra L, Tabbaa D. SNP genotyping using the Sequenom MassARRAY iPLEX platform. Current protocols in human genetics. 2009:2.12. 1-2.. 6.Google Scholar
  19. 19.
    Thomas RK, Baker AC, DeBiasi RM, Winckler W, LaFramboise T, Lin WM, et al. High-throughput oncogene mutation profiling in human cancer. Nat Genet. 2007;39(3):347–51.CrossRefPubMedGoogle Scholar
  20. 20.
    Adamec C. Example of the use of the nonparametric test. test X 2 for comparison of 2 independent examples. Cesk Zdrav. 1964;12:613–9.PubMedGoogle Scholar
  21. 21.
    Bland JM, Altman DG. Statistics notes: the odds ratio. BMJ Br Med J. 2000;320(7247):1468.CrossRefGoogle Scholar
  22. 22.
    Solé X, Guinó E, Valls J, Iniesta R, Moreno V. SNPStats: a web tool for the analysis of association studies. Bioinformatics. 2006;22(15):1928–9.CrossRefPubMedGoogle Scholar
  23. 23.
    Frusch N, Bosquee L, Louis R. Lung cancer. Epidemiology and etiologic factors. Rev Med Liege. 2007;62(9):548–53.PubMedGoogle Scholar
  24. 24.
    Hecht SS. Progress and challenges in selected areas of tobacco carcinogenesis. Chem Res Toxicol. 2008;21(1):160–71. doi: 10.1021/tx7002068.CrossRefPubMedGoogle Scholar
  25. 25.
    Improgo MR, Tapper AR, Gardner PD. Nicotinic acetylcholine receptor-mediated mechanisms in lung cancer. Biochem Pharmacol. 2011;82(8):1015–21.CrossRefPubMedGoogle Scholar
  26. 26.
    Saccone NL, Wang JC, Breslau N, Johnson EO, Hatsukami D, Saccone SF, et al. The CHRNA5-CHRNA3-CHRNB4 nicotinic receptor subunit gene cluster affects risk for nicotine dependence in African-Americans and in European-Americans. Cancer Res. 2009;69(17):6848–56.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Weiss RB, Baker TB, Cannon DS, von Niederhausern A, Dunn DM, Matsunami N, et al. A candidate gene approach identifies the CHRNA5-A3-B4 region as a risk factor for age-dependent nicotine addiction. PLoS Genet. 2008;4(7):e1000125.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Russo P, Nastrucci C, Alzetta G, Szalai C. Tobacco habit: historical, cultural, neurobiological, and genetic features of people's relationship with an addictive drug. Perspect Biol Med. 2011;54(4):557–77.CrossRefPubMedGoogle Scholar
  29. 29.
    Wang Y, Broderick P, Matakidou A, Eisen T, Houlston RS. Chromosome 15q25 (CHRNA3-CHRNA5) variation impacts indirectly on lung cancer risk. PLoS One. 2011;6(4):e19085.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Wenjing Zhou
    • 1
  • Tingting Geng
    • 2
  • Huijuan Wang
    • 1
    • 2
  • Xiaojie Xun
    • 1
  • Tian Feng
    • 2
  • Hui Zou
    • 2
  • Longli Kang
    • 3
  • Tianbo Jin
    • 1
    • 2
    • 3
  • Chao Chen
    • 1
    • 2
  1. 1.School of Life SciencesNorthwest UniversityXi’anChina
  2. 2.National Engineering Research Center for Miniaturized Detection SystemsXi’anChina
  3. 3.Key Laboratory of High Altitude Environment and Genes Related to Diseases of Tibet Autonomous Region, School of MedicineTibet University for NationalitiesXianyangChina

Personalised recommendations