Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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CHRNA5 rs16969968 Polymorphism Association with Risk of Lung Cancer - Evidence from 17,962 Lung Cancer Cases and 77,216 Control Subjects

  • Xu, Zhi-Wei (Department of Critical Care Medicine, Ningbo Medical Center, Lihuili Hospital) ;
  • Wang, Guan-Nan (Department of Gynaecology, Ningbo Medical Center, Lihuili Hospital) ;
  • Dong, Zhou-Zhou (Department of Critical Care Medicine, Ningbo Medical Center, Lihuili Hospital) ;
  • Li, Tao-Hong (Department of Critical Care Medicine, Ningbo Medical Center, Lihuili Hospital) ;
  • Cao, Chao (Department of Respiratory Medicine, Affiliated Hospital of School of Medicine, Ningbo University) ;
  • Jin, Yu-Hong (Department of Critical Care Medicine, Ningbo Medical Center, Lihuili Hospital)
  • Published : 2015.10.06
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Abstract

Background: Genetic studies have shown a possible relationship between the rs16969968 polymorphism in CHRNA5 and the risk of lung cancer. However, the results have been conflicting. Thus we rigorously conducted a meta-analysis to clarify any association. Materials and Methods: A total of 10 case-control studies involving 17,962 lung cancer cases and 77,216 control subjects were analysed. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to measure the strength of the association. Results: We found the CHRNA5 rs16969968 polymorphism to be associated with the risk of lung cancer (AA vs GG: OR=1.60, 95%CI=1.51-1.71). On stratified analysis by smoking status, a statistically significant increased risk was observed in the smoking group (AA vs GG: OR=1.80, 95%CI=1.61-2.01). However, this polymorphism was not associated with lung cancer risk in Asians (AA vs GG: OR=0.95, 95%CI=0.35-2.59), whereas it was linked to increased risk of lung cancer among Caucasians (AA vs GG: OR=1.65, 95%CI=1.55-1.76). Conclusions: Our meta-analysis provided statistical evidence for a strong association between rs16969968 polymorphism and the risk of lung cancer, especially in smokers and Caucasians. Application of this relationship may contribute to identification of individuals at high risk of lung cancer and indicate a chemoprevention target.

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References

  1. Ahmad D, Bakairy AK, Katheri AM, et al (2015). MDM2 (RS769412) G>A Polymorphism in cigarette smokers: a clue for the susceptibility to smoking and lung cancer risk. Asian Pac J Cancer Prev, 16, 4057-60. https://doi.org/10.7314/APJCP.2015.16.9.4057
  2. Bierut LJ, Stitzel JA, Wang JC, et al (2008). Variants in Nicotinic Receptors and Risk for Nicotine Dependence. Am J Psychiat, 165, 1163-71. https://doi.org/10.1176/appi.ajp.2008.07111711
  3. Cao C, Sun SF, Lv D, et al (2013). Utility of VEGF and sVEGFR-1 in bronchoalveolar lavage fluid for differential diagnosis of primary lung cancer. Asian Pac J Cancer Prev, 14, 2443-6. https://doi.org/10.7314/APJCP.2013.14.4.2443
  4. Cao C, Wang R, Wang J, et al (2012). Body mass index and mortality in chronic obstructive pulmonary disease: a metaanalysis. PLoS One, 7, 43892. https://doi.org/10.1371/journal.pone.0043892
  5. Carcereny E, Ramirez JL, Sanchez-Ronco M, et al (2010). Blood-based CHRNA3 single nucleotide polymorphism and outcome in advanced non-small-cell lung cancer patients. Lung Cancer-J Iaslc, 68, 491-7. https://doi.org/10.1016/j.lungcan.2009.08.004
  6. Chen Z, Xu Z, Sun S, et al (2014). TGF-beta1, IL-6, and TNFalpha in bronchoalveolar lavage fluid: useful markers for lung cancer? Sci Rep, 4, 5595.
  7. Dasgupta P, Kinkade R, Joshi B, et al (2006). Nicotine inhibits apoptosis induced by chemotherapeutic drugs by upregulating XIAP and survivin. Proc Natl Acad Sci U S A, 103, 6332-7. https://doi.org/10.1073/pnas.0509313103
  8. Dasgupta P, Rizwani W, Pillai S, et al (2009). Nicotine induces cell proliferation, invasion and epithelial-mesenchymal transition in a variety of human cancer cell lines. Int J Cancer, 124, 36-45. https://doi.org/10.1002/ijc.23894
  9. Egger M, Davey SG, Schneider M, et al (1997). Bias in metaanalysis detected by a simple, graphical test. BMJ, 315, 629-34. https://doi.org/10.1136/bmj.315.7109.629
  10. Falvella FS, Galvan A, Frullanti E, et al (2009). Transcription deregulation at the 15q25 locus in association with lung adenocarcinoma risk. Clin Cancer Res, 15, 1837-42. https://doi.org/10.1158/1078-0432.CCR-08-2107
  11. Fowler CD, Lu Q, Johnson PM, et al (2011). Habenular alpha5 nicotinic receptor subunit signalling controls nicotine intake. Nature, 471, 597-601. https://doi.org/10.1038/nature09797
  12. Gabrielsen ME, Romundstad P, Langhammer A, et al (2013). Association between a 15q25 gene variant, nicotine-related habits, lung cancer and COPD among 56,307 individuals from the HUNT study in Norway. Eur J Hum Genet, 21, 1293-9. https://doi.org/10.1038/ejhg.2013.26
  13. Hansen HM, Xiao Y, Rice T, et al (2010). Fine mapping of chromosome 15q25.1 lung cancer susceptibility in African-Americans. Hum Mol Genet, 19, 3652-61. https://doi.org/10.1093/hmg/ddq268
  14. He P, Yang XX, He XQ, et al (2014). CHRNA3 Polymorphism Modifies Lung Adenocarcinoma Risk in the Chinese Han Population. Int J Mol Sci, 15, 5446-57. https://doi.org/10.3390/ijms15045446
  15. Higgins JP, Thompson SG (2002). Quantifying heterogeneity in a meta-analysis. Stat Med, 21, 1539-58. https://doi.org/10.1002/sim.1186
  16. Higgins JP, Thompson SG, Deeks JJ, et al (2003). Measuring inconsistency in meta-analyses. BMJ, 327, 557-60. https://doi.org/10.1136/bmj.327.7414.557
  17. Hung RJ, McKay JD, Gaborieau V, et al (2008). A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25. Nature, 452, 633-7. https://doi.org/10.1038/nature06885
  18. Islam MS, Ahmed MU, Sayeed MS, et al (2013). Lung cancer risk in relation to nicotinic acetylcholine receptor, CYP2A6 and CYP1A1 genotypes in the Bangladeshi population. Clin Chim Acta, 416, 11-19. https://doi.org/10.1016/j.cca.2012.11.011
  19. Jaworowska E, Trubicka J, Lener MR, et al (2011). Smoking related cancers and loci at chromosomes 15q25, 5p15, 6p22.1 and 6p21.33 in the Polish population. PLoS One, 6, 25057. https://doi.org/10.1371/journal.pone.0025057
  20. Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90. https://doi.org/10.3322/caac.20107
  21. Le Marchand L, Derby KS, Murphy SE, et al (2008). Smokers with the CHRNA lung cancer-associated variants are exposed to higher levels of nicotine equivalents and a carcinogenic tobacco-specific nitrosamine. Cancer Res, 68, 9137-40. https://doi.org/10.1158/0008-5472.CAN-08-2271
  22. Lips EH, Gaborieau V, McKay JD, et al (2010). Association between a 15q25 gene variant, smoking quantity and tobacco-related cancers among 17 000 individuals. Int J Epidemiol, 39, 563-577. https://doi.org/10.1093/ije/dyp288
  23. Liu JZ, Tozzi F, Waterworth DM, et al (2010). Meta-analysis and imputation refines the association of 15q25 with smoking quantity. Nat Genet, 42, 436-40. https://doi.org/10.1038/ng.572
  24. Macqueen DA, Heckman BW, Blank MD, et al (2014). Variation in the alpha 5 nicotinic acetylcholine receptor subunit gene predicts cigarette smoking intensity as a function of nicotine content. Pharmacogenomics J, 14, 70-76. https://doi.org/10.1038/tpj.2012.50
  25. Saccone NL, Saccone SF, Hinrichs AL, et al (2009). Multiple distinct risk loci for nicotine dependence identified by dense coverage of the complete family of nicotinic receptor subunit (CHRN) genes. Am J Med Genet B Neuropsychiatr Genet, 150, 453-66.
  26. Saccone SF, Hinrichs AL, Saccone NL, et al (2007). Cholinergic nicotinic receptor genes implicated in a nicotine dependence association study targeting 348 candidate genes with 3713 SNPs. Hum Mol Genet, 16, 36-49.
  27. Sakoda LC, Loomis MM, Doherty JA, et al (2011). Chromosome 15q24-25.1 variants, diet, and lung cancer susceptibility in cigarette smokers. Cancer Causes Control, 22, 449-61. https://doi.org/10.1007/s10552-010-9716-1
  28. Sasaki H, Hikosaka Y, Okuda K, et al (2010). CHRNA5 gene D398N polymorphism in Japanese lung adenocarcinoma. J Surg Res, 162, 75-78. https://doi.org/10.1016/j.jss.2009.01.008
  29. Shiraishi K, Kohno T, Kunitoh H, et al (2009). Contribution of nicotine acetylcholine receptor polymorphisms to lung cancer risk in a smoking-independent manner in the Japanese. Carcinogenesis, 30, 65-70.
  30. Spitz MR, Amos CI, Land S, et al (2013). Role of selected genetic variants in lung cancer risk in African Americans. J Thorac Oncol, 8, 391-7. https://doi.org/10.1097/JTO.0b013e318283da29
  31. Timofeeva MN, McKay JD, Smith GD, et al (2011). Genetic polymorphisms in 15q25 and 19q13 loci, cotinine levels, and risk of lung cancer in EPIC. Cancer Epidemiol Biomarkers Prev, 20, 2250-61. https://doi.org/10.1158/1055-9965.EPI-11-0496
  32. Toh CK, Gao F, Lim WT, et al (2006). Never-smokers with lung cancer: epidemiologic evidence of a distinct disease entity. J Clin Oncol, 24, 2245-51. https://doi.org/10.1200/JCO.2005.04.8033
  33. Truong T, Hung RJ, Amos CI, et al (2010). 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, 102, 959-971. https://doi.org/10.1093/jnci/djq178
  34. Walsh KM, Gorlov IP, Hansen HM, et al (2013). Fine-mapping of the 5p15.33, 6p22.1-p21.31, and 15q25.1 regions identifies functional and histology-specific lung cancer susceptibility loci in African-Americans. Cancer Epidemiol Biomarkers Prev, 22, 251-60. https://doi.org/10.1158/1055-9965.EPI-12-1007-T
  35. Ware JJ, van den Bree MB, Munafo MR (2011). Association of the CHRNA5-A3-B4 gene cluster with heaviness of smoking: a meta-analysis. Nicotine Tob Res, 13, 1167-75. https://doi.org/10.1093/ntr/ntr118
  36. Wei C, Han Y, Spitz MR, et al (2011). A case-control study of a sex-specific association between a 15q25 variant and lung cancer risk. Cancer Epidemiol Biomarkers Prev, 20, 2603-9. https://doi.org/10.1158/1055-9965.EPI-11-0749
  37. Weiss RB, Baker TB, Cannon DS, et al (2008). A candidate gene approach identifies the CHRNA5-A3-B4 region as a risk factor for age-dependent nicotine addiction. PLoS Genet, 4, 1000125. https://doi.org/10.1371/journal.pgen.1000125
  38. Wojas-Krawczyk K, Krawczyk P, Biernacka B, et al (2012). The polymorphism of the CHRNA5 gene and the strength of nicotine addiction in lung cancer and COPD patients. Eur J Cancer Prev, 21, 111-7. https://doi.org/10.1097/CEJ.0b013e32834c9b40
  39. Yang P, Li Y, Jiang R, et al (2010). A rigorous and comprehensive validation: common genetic variations and lung cancer. Cancer Epidemiol Biomarkers Prev, 19, 240-4. https://doi.org/10.1158/1055-9965.EPI-09-0710
  40. Young RP, Hopkins RJ, Hay BA, et al (2008). Lung cancer gene associated with COPD: triple whammy or possible confounding effect? Eur Respir J, 32, 1158-64. https://doi.org/10.1183/09031936.00093908
  41. Zienolddiny S, Skaug V, Landvik NE, et al (2009). The TERTCLPTM1L lung cancer susceptibility variant associates with higher DNA adduct formation in the lung. Carcinogenesis, 30, 1368-71. https://doi.org/10.1093/carcin/bgp131

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