Skip to main content

Advertisement

SpringerLink
Log in

Neuronal acetylcholine receptor subunit alpha-9 (CHRNA9) polymorphisms are associated with NSCLC risk in a Chinese population

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

Neuronal acetylcholine receptor subunit alpha-9 (CHRNA9) encodes a plasma membrane protein of divalent cation channels and is expressed in keratinocytes. This study aimed to investigate CHRNA9 single-nucleotide polymorphisms (SNPs) for association with non-small cell lung cancer (NSCLC), especially squamous cell carcinoma (SCC) risk, in a Chinese population. This case–control study included 500 NSCLC patients and 500 age-matched healthy controls. CHRNA9 rs56159866, rs6819385, rs55998310, and rs182073550 SNPs were genotyped and associated for NSCLC risk by computing the odds ratios (ORs) and 95 % confidence intervals (CIs) from multivariate unconditional logistic regression analyses with adjustment for age. The frequencies of the CHRNA9 rs6819385 G allele were 16.1, 15.2, and 20.8 % in male NSCLC patients, male SCC patients, and male controls, respectively. The CHRNA9 rs6819385 A allele was associated with an increased risk of developing NSCLC (P = 0.04, OR = 1.37; 95 % CI 1.02–1.83) and SCC (P = 0.04, OR = 1.47; 95 % CI 1.01–2.13). The CHRNA9 rs6819385 A/A homozygote was associated with an increased risk of NSCLC and SCC in all patients (OR = 1.38; 95 % CI 1.06–1.79; P = 0.02, and OR = 1.61; 95 % CI 1.09–2.38; P = 0.02, respectively) and in male patients (OR = 1.57; 95 % CI 1.11–2.21; P = 0.01, and OR = 1.70; 95 % CI 1.11–2.61; P = 0.01, respectively), indicating that the CHRNA9 rs6819385 A/A homozygote had a 1.61-fold and 1.70-fold increased risk of developing lung SCC in all patients (95 % CI 1.09–2.38, P = 0.02) and in males (95 % CI 1.11–2.61, P = 0.01), respectively. The CHRNA9 rs6819385 SNP was significantly associated with an increased risk of NSCLC, especially for SCC in male patients in this Chinese population.

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

Similar content being viewed by others

References

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.

    Article  PubMed  Google Scholar 

  2. Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA. Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc. 2008;83:584–94.

    Article  PubMed Central  PubMed  Google Scholar 

  3. Frusch N, Bosquée L, Louis R. Lung cancer, epidemiology and etiologic factor. Rev Med Liege. 2007;62:548–53.

    CAS  PubMed  Google Scholar 

  4. Brennan P, Buffler PA, Reynolds P, Wu AH, Wichmann HE, Agudo A, et al. Secondhand smoke exposure in adulthood and risk of lung cancer among never smokers: a pooled analysis of two large studies. Int J Cancer. 2004;109:125–31.

    Article  CAS  PubMed  Google Scholar 

  5. Darby S, Hill D, Auvinen A, Barros-Dios JM, Baysson H, Bochicchio F, et al. Radon in homes and risk of lung cancer: collaborative analysis of individual data from 13 European case-control studies. BMJ. 2005;330:223.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Lan Q, Chapman RS, Schreinemachers DM, Tian L, He X. Household stove improvement and risk of lung cancer in Xuanwei, China. J Natl Cancer Inst. 2002;94:826–35.

    Article  PubMed  Google Scholar 

  7. Bailey-Wilson JE, Amos CI, Pinney SM, Petersen GM, de Andrade M, Wiest JS, et al. A major lung cancer susceptibility locus maps to chromosome 6q23-25. Am J Hum Genet. 2004;75:460–74.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. 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;40:616–22.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. 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.

    Article  CAS  PubMed  Google Scholar 

  10. Thorgeirsson TE, Geller F, Sulem P, Rafnar T, Wiste A, Magnusson KP, et al. A variant associated with nicotine dependence, lung cancer and peripheral arterial disease. Nature. 2008;452:638–42.

    Article  CAS  PubMed  Google Scholar 

  11. 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.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. 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.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. 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.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Hansen HM, Xiao YY, Rice T, Bracci PM, Wrensch MR, Sison JD, et al. Fine mapping of chromosome 15q25.1 lung cancer susceptibility in African–Americans. Hum Mol Genet. 2009;19:3652–61.

    Article  Google Scholar 

  15. Li Z, Bao S, Xu X, Bao Y, Zhang Y. Polymorphisms of CHRNA5-CHRNA3-CHRNB4 gene cluster and NSCLC risk in chinese population. Transl Oncol. 2012;5:448–52.

    Article  PubMed Central  PubMed  Google Scholar 

  16. Nguyen VT, Ndoye A, Grando SA. Novel human 9 acetylcholine receptor regulating keratinocyte adhesion is targeted by pemphigus vulgaris autoimmunity. Am J Pathol. 2000;157:1377–91.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Lee CH, Huang CS, Chen CS, Tu SH, Wang YJ, Chang YJ, et al. Overexpression and activation of the alpha9-nicotinic receptor during tumorigenesis in human breast epithelial cells. J Natl Cancer Inst. 2010;102:1322–35.

    Article  CAS  PubMed  Google Scholar 

  18. Wu CH, Lee CH, Ho YS. Nicotinic acetylcholine receptor-based blockade: applications of molecular target for cancer therapy. Clin Cancer Res. 2011;17:3533–4.

    Article  CAS  PubMed  Google Scholar 

  19. Chikova A, Bernard HU, Shchepotin IB, Grando SA. New associations of the genetic polymorphisms in nicotinic receptor genes with the risk of lung cancer. Life Sci. 2012;91:1103–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Pesch B, Kendzia B, Gustavsson P, Jöckel KH, Johnen G, Pohlabeln H, et al. Cigarette smoking and lung cancer–relative risk estimates for the major histological types from a pooled analysis of case-control studies. Int J Cancer. 2012;131:1210–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Zhang Y, Hua S, Zhang A, Kong X, Jiang C, Deng D, et al. Association between polymorphisms in COMT, PLCH1, and CYP17A1, and non-small-cell lung cancer risk in Chinese nonsmokers. Clin Lung Cancer. 2013;14:45–9.

    Article  PubMed  Google Scholar 

  22. Lustig LR, Peng H. Chromosome location and characterization of the human nicotinic acetylcholine receptor subunit alpha (alpha) 9 (CHRNA9) gene. Cytogenet Genome Res. 2002;98:154–9.

    Article  CAS  PubMed  Google Scholar 

  23. Peng H, Ferris RL, Matthews T, Hiel H, Lopez-Albaitero A, Lustig LR. Characterization of the human nicotinic acetylcholine receptor subunit alpha (alpha) 9 (CHRNA9) and alpha (alpha) 10 (CHRNA10) in lymphocytes. Life Sic. 2004;76:263–80.

    Article  CAS  Google Scholar 

  24. Wala EP, Crooks PA, McIntosh JM, Holtman JR. Novel small molecule alpha9 alpha10 nicotinic receptor antagonist prevents and reverses chemotherapy-evoked neuropathic pain in rats. Anesth Analg. 2012;115:713–20.

    CAS  PubMed  Google Scholar 

  25. Greenbaum L, Kanyas K, Karni O, Merbl Y, Olender T, Horowitz A, et al. Why do young women smoke? I. Direct and interactive effects of environment, psychological characteristics and nicotinic cholinergic receptor genes. Mol Psychiatry. 2006;11:312–22.

    Article  CAS  PubMed  Google Scholar 

  26. Chen CS, Lee CH, Hsieh CD, Ho CT, Pan MH, Huang CS, et al. Nicotine-induced human breast cancer cell proliferation attenuated by garcinol through down-regulation of the nicotinic receptor and cyclin D3 proteins. Breast Cancer Res Treat. 2011;125:73–87.

    Article  CAS  PubMed  Google Scholar 

  27. Lee CH, Chang YC, Chen CS, Tu SH, Wang YJ, Chen LC, et al. Crosstalk between nicotine and estrogen-induced estrogen receptor activation induces alpha9-nicotinic acetylcholine receptor expression in human breast cancer cells. Breast Cancer Res Treat. 2011;129:331–45.

    Article  CAS  PubMed  Google Scholar 

  28. Shih YL, Liu HC, Chen CS, Hsu CH, Pan MH, Chang HW, et al. Combination treatment with luteolin and quercetin enhances antiproliferative effects in nicotine-treated MDA-MB-231 cells by down-regulating nicotinic acetylcholine receptors. J Agric Food Chem. 2010;58:235–41.

    Article  CAS  PubMed  Google Scholar 

  29. Chikova A, Grando SA. Naturally occurring variants of human Alpha9 nicotinic receptor differentially affect bronchial cell proliferation and transformation. PLoS ONE. 2011;6:e27978.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Conflict of interest

The authors declared that there is no conflict of interest in this work.

Author information

Authors and Affiliations

  1. Department of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, China

    Ying Wang

  2. Department of Integration of Traditional Chinese and Western Medicine, Zhejiang Cancer Hospital, 38 Banshan Road, Hangzhou, 310022, China

    Yongjun Zhang & Wenlong Bao

  3. Department of Chemotherapy, Zhejiang Cancer Hospital, Hangzhou, China

    Cuiping Gu

  4. Clinical Laboratory, Zhejiang Cancer Hospital, Hangzhou, China

    Yejiang Bao

Authors
  1. Ying Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yongjun Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cuiping Gu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wenlong Bao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yejiang Bao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yongjun Zhang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, Y., Zhang, Y., Gu, C. et al. Neuronal acetylcholine receptor subunit alpha-9 (CHRNA9) polymorphisms are associated with NSCLC risk in a Chinese population. Med Oncol 31, 932 (2014). https://doi.org/10.1007/s12032-014-0932-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-014-0932-5

Keywords

Search

Navigation