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 Dienemann & 36 others Brittni 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

Research output: Contribution to journalReview article

35 Citations (Scopus)

Abstract

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 (US)
Article numberdjv100
JournalJournal of the National Cancer Institute
Volume107
Issue number5
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

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Smoking Cessation
Early Detection of Cancer
Meta-Analysis
Lung Neoplasms
Genotype
Smoking
Confidence Intervals
Phenotype
Proportional Hazards Models
Public Health
Chromosomes
Alleles
Drug Therapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Chen, L. S., Hung, R. J., Baker, T., Horton, A., Culverhouse, R., Saccone, N., ... Bierut, L. J. (2015). CHRNA5 Risk variant predicts delayed smoking cessation and earlier lung cancer diagnosis-a meta-analysis. Journal of the National Cancer Institute, 107(5), [djv100]. https://doi.org/10.1093/jnci/djv100

CHRNA5 Risk variant predicts delayed smoking cessation and earlier lung cancer diagnosis-a meta-analysis. / Chen, Li Shiun; Hung, Rayjean J.; Baker, Timothy; Horton, Amy; Culverhouse, Rob; Saccone, Nancy; Cheng, Iona; Deng, Bo; Han, Younghun; Hansen, Helen M.; Horsman, Janet; Kim, Claire; Lutz, Sharon; Rosenberger, Albert; Aben, Katja K.; Andrew, Angeline S.; Breslau, Naomi; Chang, Shen Chih; Dieffenbach, Aida Karina; Dienemann, Hendrik; Frederiksen, Brittni; Han, Jiali; Hatsukami, Dorothy K.; Johnson, Eric O.; Pande, Mala; Wrensch, Margaret R.; McLaughlin, John; Skaug, Vidar; Van Der Heijden, Henricus F.; Wampfler, Jason; Wenzlaff, Angela; Woll, Penella; Zienolddiny, Shanbeh; Bickeböller, Heike; Brenner, Hermann; Duell, Eric J.; Haugen, Aage; Heinrich, Joachim; Hokanson, John E.; Hunter, David J.; Kiemeney, Lambertus A.; Lazarus, Philip; Le Marchand, Loic; Liu, Geoffrey; Mayordomo, Jose; Risch, Angela; Schwartz, Ann G.; Teare, Dawn; Wu, Xifeng; Wiencke, John K.; Yang, Ping; Zhang, Zuo Feng; Spitz, Margaret R.; Kraft, Peter; Amos, Christopher I.; Bierut, Laura J.

In: Journal of the National Cancer Institute, Vol. 107, No. 5, djv100, 01.01.2015.

Research output: Contribution to journalReview article

Chen, LS, Hung, RJ, Baker, T, Horton, A, Culverhouse, R, Saccone, N, Cheng, I, Deng, B, Han, Y, Hansen, HM, Horsman, J, Kim, C, Lutz, S, Rosenberger, A, Aben, KK, Andrew, AS, Breslau, N, Chang, SC, Dieffenbach, AK, Dienemann, H, Frederiksen, B, Han, J, Hatsukami, DK, Johnson, EO, Pande, M, Wrensch, MR, McLaughlin, J, Skaug, V, Van Der Heijden, HF, Wampfler, J, Wenzlaff, A, Woll, P, Zienolddiny, S, Bickeböller, H, Brenner, H, Duell, EJ, Haugen, A, Heinrich, J, Hokanson, JE, Hunter, DJ, Kiemeney, LA, Lazarus, P, Le Marchand, L, Liu, G, Mayordomo, J, Risch, A, Schwartz, AG, Teare, D, Wu, X, Wiencke, JK, Yang, P, Zhang, ZF, Spitz, MR, Kraft, P, Amos, CI & Bierut, LJ 2015, 'CHRNA5 Risk variant predicts delayed smoking cessation and earlier lung cancer diagnosis-a meta-analysis', Journal of the National Cancer Institute, vol. 107, no. 5, djv100. https://doi.org/10.1093/jnci/djv100
Chen, Li Shiun ; Hung, Rayjean J. ; Baker, Timothy ; Horton, Amy ; Culverhouse, Rob ; Saccone, Nancy ; Cheng, Iona ; Deng, Bo ; Han, Younghun ; Hansen, Helen M. ; Horsman, Janet ; Kim, Claire ; Lutz, Sharon ; Rosenberger, Albert ; Aben, Katja K. ; Andrew, Angeline S. ; Breslau, Naomi ; Chang, Shen Chih ; Dieffenbach, Aida Karina ; Dienemann, Hendrik ; Frederiksen, Brittni ; Han, Jiali ; Hatsukami, Dorothy K. ; Johnson, Eric O. ; Pande, Mala ; Wrensch, Margaret R. ; McLaughlin, John ; Skaug, Vidar ; Van Der Heijden, Henricus F. ; Wampfler, Jason ; Wenzlaff, Angela ; Woll, Penella ; Zienolddiny, Shanbeh ; Bickeböller, Heike ; Brenner, Hermann ; Duell, Eric J. ; Haugen, Aage ; Heinrich, Joachim ; Hokanson, John E. ; Hunter, David J. ; Kiemeney, Lambertus A. ; Lazarus, Philip ; Le Marchand, Loic ; Liu, Geoffrey ; Mayordomo, Jose ; Risch, Angela ; Schwartz, Ann G. ; Teare, Dawn ; Wu, Xifeng ; Wiencke, John K. ; Yang, Ping ; Zhang, Zuo Feng ; Spitz, Margaret R. ; Kraft, Peter ; Amos, Christopher I. ; Bierut, Laura J. / CHRNA5 Risk variant predicts delayed smoking cessation and earlier lung cancer diagnosis-a meta-analysis. In: Journal of the National Cancer Institute. 2015 ; Vol. 107, No. 5.
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abstract = "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.",
author = "Chen, {Li Shiun} and Hung, {Rayjean J.} and Timothy Baker and Amy Horton and Rob Culverhouse and Nancy Saccone and Iona Cheng and Bo Deng and Younghun Han and Hansen, {Helen M.} and Janet Horsman and Claire Kim and Sharon Lutz and Albert Rosenberger and Aben, {Katja K.} and Andrew, {Angeline S.} and Naomi Breslau and Chang, {Shen Chih} and Dieffenbach, {Aida Karina} and Hendrik Dienemann and Brittni Frederiksen and Jiali Han and Hatsukami, {Dorothy K.} and Johnson, {Eric O.} and Mala Pande and Wrensch, {Margaret R.} and John McLaughlin and Vidar Skaug and {Van Der Heijden}, {Henricus F.} and Jason Wampfler and Angela Wenzlaff and Penella Woll and Shanbeh Zienolddiny and Heike Bickeb{\"o}ller and Hermann Brenner and Duell, {Eric J.} and Aage Haugen and Joachim Heinrich and Hokanson, {John E.} and Hunter, {David J.} and Kiemeney, {Lambertus A.} and Philip Lazarus and {Le Marchand}, Loic and Geoffrey Liu and Jose Mayordomo and Angela Risch and Schwartz, {Ann G.} and Dawn Teare and Xifeng Wu and Wiencke, {John K.} and Ping Yang and Zhang, {Zuo Feng} and Spitz, {Margaret R.} and Peter Kraft and Amos, {Christopher I.} and Bierut, {Laura J.}",
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TY - JOUR

T1 - CHRNA5 Risk variant predicts delayed smoking cessation and earlier lung cancer diagnosis-a meta-analysis

AU - Chen, Li Shiun

AU - Hung, Rayjean J.

AU - Baker, Timothy

AU - Horton, Amy

AU - Culverhouse, Rob

AU - Saccone, Nancy

AU - Cheng, Iona

AU - Deng, Bo

AU - Han, Younghun

AU - Hansen, Helen M.

AU - Horsman, Janet

AU - Kim, Claire

AU - Lutz, Sharon

AU - Rosenberger, Albert

AU - Aben, Katja K.

AU - Andrew, Angeline S.

AU - Breslau, Naomi

AU - Chang, Shen Chih

AU - Dieffenbach, Aida Karina

AU - Dienemann, Hendrik

AU - Frederiksen, Brittni

AU - Han, Jiali

AU - Hatsukami, Dorothy K.

AU - Johnson, Eric O.

AU - Pande, Mala

AU - Wrensch, Margaret R.

AU - McLaughlin, John

AU - Skaug, Vidar

AU - Van Der Heijden, Henricus F.

AU - Wampfler, Jason

AU - Wenzlaff, Angela

AU - Woll, Penella

AU - Zienolddiny, Shanbeh

AU - Bickeböller, Heike

AU - Brenner, Hermann

AU - Duell, Eric J.

AU - Haugen, Aage

AU - Heinrich, Joachim

AU - Hokanson, John E.

AU - Hunter, David J.

AU - Kiemeney, Lambertus A.

AU - Lazarus, Philip

AU - Le Marchand, Loic

AU - Liu, Geoffrey

AU - Mayordomo, Jose

AU - Risch, Angela

AU - Schwartz, Ann G.

AU - Teare, Dawn

AU - Wu, Xifeng

AU - Wiencke, John K.

AU - Yang, Ping

AU - Zhang, Zuo Feng

AU - Spitz, Margaret R.

AU - Kraft, Peter

AU - Amos, Christopher I.

AU - Bierut, Laura J.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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.

AB - 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.

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U2 - 10.1093/jnci/djv100

DO - 10.1093/jnci/djv100

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JO - Journal of the National Cancer Institute

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