CHRNA5 Risk variant predicts delayed smoking cessation and earlier lung cancer diagnosis-a meta-analysis

Li Shiun Chen, Rayjean J. Hung, Timothy Baker, Amy Horton, Rob Culverhouse, Nancy Saccone, Iona Cheng, Bo Deng, Younghun Han, Helen M. Hansen, Janet Horsman, Claire Kim, Sharon Lutz, Albert Rosenberger, Katja K. Aben, Angeline S. Andrew, Naomi Breslau, Shen Chih Chang, Aida Karina Dieffenbach, Hendrik DienemannBrittni Frederiksen, Jiali Han, Dorothy K. Hatsukami, Eric O. Johnson, Mala Pande, Margaret R. Wrensch, John McLaughlin, Vidar Skaug, Henricus F. Van Der Heijden, Jason Wampfler, Angela Wenzlaff, Penella Woll, Shanbeh Zienolddiny, Heike Bickeböller, Hermann Brenner, Eric J. Duell, Aage Haugen, Joachim Heinrich, John E. Hokanson, David J. Hunter, Lambertus A. Kiemeney, Philip Lazarus, Loic Le Marchand, Geoffrey Liu, Jose Mayordomo, Angela Risch, Ann G. Schwartz, Dawn Teare, Xifeng Wu, John K. Wiencke, Ping Yang, Zuo Feng Zhang, Margaret R. Spitz, Peter Kraft, Christopher I. Amos, Laura J. Bierut

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63 Scopus citations


Background: Recent meta-analyses show strong evidence of associations among genetic variants in CHRNA5 on chromosome 15q25, smoking quantity, and lung cancer. This meta-analysis tests whether the CHRNA5 variant rs16969968 predicts age of smoking cessation and age of lung cancer diagnosis. Methods: Meta-analyses examined associations between rs16969968, age of quitting smoking, and age of lung cancer diagnosis in 24 studies of European ancestry (n = 29 072). In each dataset, we used Cox regression models to evaluate the association between rs16969968 and the two primary phenotypes (age of smoking cessation among ever smokers and age of lung cancer diagnosis among lung cancer case patients) and the secondary phenotype of smoking duration. Heterogeneity across studies was assessed with the Cochran Q test. All statistical tests were two-sided. Results: The rs16969968 allele (A) was associated with a lower likelihood of smoking cessation (hazard ratio [HR] = 0.95, 95% confidence interval [CI] = 0.91 to 0.98, P =. 0042), and the AA genotype was associated with a four-year delay in median age of quitting compared with the GG genotype. Among smokers with lung cancer diagnoses, the rs16969968 genotype (AA) was associated with a four-year earlier median age of diagnosis compared with the low-risk genotype (GG) (HR = 1.08, 95% CI = 1.04 to 1.12, P = 1.1∗10-5). Conclusion: These data support the clinical significance of the CHRNA5 variant rs16969968. It predicts delayed smoking cessation and an earlier age of lung cancer diagnosis in this meta-analysis. Given the existing evidence that this CHRNA5 variant predicts favorable response to cessation pharmacotherapy, these findings underscore the potential clinical and public health importance of rs16969968 in CHRNA5 in relation to smoking cessation success and lung cancer risk.

Original languageEnglish
JournalJournal of the National Cancer Institute
Issue number5
StatePublished - May 1 2015


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