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Is susceptibility locus for lung cancer in the 15q25 nicotinic acetylcholine receptor gene cluster CHRNA5-A3-B4 associated with risk of gastric cancer?

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Abstract

An association between common variants in the 15q25 nicotinic acetylcholine receptor (nAChR) gene cluster CHRNA5-A3-B4 (responsible for encoding nAChR subunits) and lung cancer risk has recently been reported in both Caucasian and Chinese population. Cigarette smoking is one of the major risk factors for both lung and gastric cancer. Moreover, nAChR plays an important role in cigarette smoke-related lung carcinogenesis as well as gastric cancer. Nevertheless, no study has evaluated the association between CHRNA5-A3-B4 gene cluster variants (rs667282 and rs3743073, two variants modifying lung cancer risk) and risk of gastric cancer. We genotyped these two single nucleotide polymorphisms(SNPs) and analyzed their associations with risk of gastric cancer in a case–control study of 637 gastric cancer patients and 855 healthy individuals matched by age and sex in a Chinese Han population. The differences in genotype distribution of the two SNPs (rs667282, rs3743073) between the cases and controls were not statistically significant (p = 0.468 and p = 0.495, respectively). Overall, we did not observe a significant association of each genotype of the two SNPs with risk of gastric cancer (TT/CT vs. CC: adjusted OR = 1.12,95 % CI = 0.86–1.45; p = 0.401 for rs667282 and GG/TG vs. TT: adjusted OR = 1.13,95 % CI = 0.90–1.43; p = 0.300 for rs3743073).The results of our study indicated that these two SNPs at the 15q25 locus did not modify gastric cancer risk and the reported risk SNP at 15q25 may be specific to lung cancer. Additional larger studies are needed to further confirm our findings.

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References

  1. Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.

    Article  PubMed  Google Scholar 

  2. Ladeiras-Lopes R, Pereira AK, Nogueira A, et al. Smoking and gastric cancer: systematic review and meta-analysis of cohort studies. Cancer Causes Control. 2008;19(7):689–701.

    Article  PubMed  Google Scholar 

  3. Trédaniel J, Boffetta P, Buiatti E, et al. Tobacco smoking and gastric cancer: review and meta-analysis. Int J Cancer. 1997;72(4):565–73.

    Article  PubMed  Google Scholar 

  4. Nishino Y, Inoue M, Tsuji I, et al. Tobacco smoking and gastric cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population. Jpn J Clin Oncol. 2006;36(12):800–7.

    Article  PubMed  Google Scholar 

  5. IARC. Tobacco smoke and involuntary smoking. IARC monographs on the evaluation of carcinogenic risk of chemicals to humans. Lyon(France): International Agency for Research on Cancer; 2004.

    Google Scholar 

  6. Amos CI, Wu X, Broderick P, 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.

    Article  PubMed  CAS  Google Scholar 

  7. Hung RJ, McKay JD, Gaborieau V, et al. A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25. Nature. 2008;452(7187):633–7.

    Article  PubMed  CAS  Google Scholar 

  8. Thorgeirsson TE, Geller F, Sulem P, et al. A variant associated with nicotine dependence, lung cancer and peripheral arterial disease. Nature. 2008;452(7187):638–42.

    Article  PubMed  CAS  Google Scholar 

  9. Wu C, Hu Z, Yu D, et al. Genetic variants on chromosome 15q25 associated with lung cancer risk in Chinese populations. Cancer Res. 2009;69(12):5065–72.

    Article  PubMed  CAS  Google Scholar 

  10. Niu X, Chen Z, Shen S, et al. Association of the CHRNA3 locus with lung cancer risk and prognosis in Chinese Han population. J Thorac Oncol. 2010;5(5):658–66.

    PubMed  Google Scholar 

  11. Shen B, Shi MQ, Zheng MQ, et al. Correlation between polymorphisms of nicotine acetylcholine acceptor subunit CHRNA3 and lung cancer susceptibility. Mol Med Rep. 2012;6(6):1389–92.

    PubMed  CAS  Google Scholar 

  12. Hecht SS. Tobacco carcinogens, their biomarkers and tobacco-induced cancer. Nat Rev Cancer. 2003;3(10):733–44.

    Article  PubMed  CAS  Google Scholar 

  13. Schuller HM. Is cancer triggered by altered signalling of nicotinic acetylcholine receptors? Nat Rev Cancer. 2009;9(3):195–205.

    Article  PubMed  CAS  Google Scholar 

  14. Egleton RD, Brown KC, Dasgupta P. Nicotinic acetylcholine receptors in cancer: multiple roles in proliferation and inhibition of apoptosis. Trends Pharmacol Sci. 2008;29(3):151–8.

    Article  PubMed  CAS  Google Scholar 

  15. Schuller HM. Nitrosamines as nicotinic receptor ligands. Life Sci. 2007;80(24–25):2274–80.

    Article  PubMed  CAS  Google Scholar 

  16. Lam DC, Girard L, Ramirez R, et al. Expression of nicotinic acetylcholine receptor subunit genes in non-small-cell lung cancer reveals differences between smokers and nonsmokers. Cancer Res. 2007;67(10):4638–47.

    Article  PubMed  CAS  Google Scholar 

  17. Shin VY, Jin HC, Ng EK, et al. Nicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone induce cyclooxygenase-2 activity in human gastric cancer cells: involvement of nicotinic acetylcholine receptor (nAChR) and beta-adrenergic receptor signaling pathways. Toxicol Appl Pharmacol. 2008;233(2):254–61.

    Article  PubMed  CAS  Google Scholar 

  18. Lien YC, Wang W, Kuo LJ, et al. Nicotine promotes cell migration through alpha7 nicotinic acetylcholine receptor in gastric cancer cells. Ann Surg Oncol. 2011;18(9):2671–9.

    Article  PubMed  Google Scholar 

  19. Wang W, Chin-Sheng H, Kuo LJ, et al. NNK enhances cell migration through α7-nicotinic acetylcholine receptor accompanied by increased of fibronectin expression in gastric cancer. Ann Surg Oncol. 2012;19(Suppl 3):S580–8.

    Article  PubMed  Google Scholar 

  20. Tekpli X, Landvik NE, Skaug V, et al. Functional effect of polymorphisms in 15q25 locus on CHRNA5 mRNA, bulky DNA adducts and TP53 mutations. Int J Cancer. 2013;132(8):1811–20.

    Article  PubMed  CAS  Google Scholar 

  21. Spitz MR, Amos CI, Dong Q, et al. The CHRNA5-A3 region on chromosome 15q24-25.1 is a risk factor both for nicotine dependence and for lung cancer. J Natl Cancer Inst. 2008;100(21):1552–6.

    Article  PubMed  CAS  Google Scholar 

  22. Chen J, Wu X, Pande M, et al. Susceptibility locus for lung cancer at 15q25.1 is not associated with risk of pancreatic cancer. Pancreas. 2011;40(6):872–5.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by the Natural Science Foundation of Shandong Province [Z2005C02]. We thank the Key Laboratory of Cardiovascular Remodeling and Function Research for their technical assistance.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Radiation Oncology, Qilu Hospital, Shandong University, 107#,Wenhua Xi Road, Jinan, 250012, Shandong Province, China

    Haijian Wu, Yang Wang, Shikun Wang, Cuihong Wang, Weijiang Fu & Likuan Hu

  2. Department of Gastroenterology, Provincial Hospital Affiliated to Shandong University, 324#, Jingwu Weiqi Road, Jinan, 250021, Shandong Province, China

    Man Jiang

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  1. Haijian Wu
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  2. Yang Wang
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  3. Shikun Wang
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  4. Man Jiang
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  5. Cuihong Wang
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  6. Weijiang Fu
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  7. Likuan Hu
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Correspondence to Likuan Hu.

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Wu, H., Wang, Y., Wang, S. et al. Is susceptibility locus for lung cancer in the 15q25 nicotinic acetylcholine receptor gene cluster CHRNA5-A3-B4 associated with risk of gastric cancer?. Med Oncol 30, 576 (2013). https://doi.org/10.1007/s12032-013-0576-x

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  • DOI: https://doi.org/10.1007/s12032-013-0576-x

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