A susceptibility locus on chromosome 6q greatly increases lung cancer risk among light and never smokers

Christopher I. Amos, Susan M. Pinney, Yafang Li, Elena Kupert, Juwon Lee, Mariza A. De Andrade, Ping Yang, Ann G. Schwartz, Pam R. Fain, Adi Gazdar, John Minna, Jonathan S. Wiest, Dong Zeng, Henry Rothschild, Diptasri Mandal, Ming You, Teresa Coons, Colette Gaba, Joan E. Bailey-Wilson, Marshall W. Anderson

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Abstract

Cigarette smoking is the major cause for lung cancer, but genetic factors also affect susceptibility. We studied families that included multiple relatives affected by lung cancer. Results from linkage analysis showed strong evidence that a region of chromosome 6q affects lung cancer risk. To characterize the effects that this region of chromosome 6q region has on lung cancer risk, we identified a haplotype that segregated with lung cancer. We then performed Cox regression analysis to estimate the differential effects that smoking behaviors have on lung cancer risk according to whether each individual carried a risk-associated haplotype or could not be classified and was assigned unknown haplotypic status. We divided smoking exposures into never smokers, light smokers (<20 pack-years), moderate smokers (20 to <40 pack-years), and heavy smokers (≥40 pack-years). Comparing results according to smoking behavior stratified by carrier status, compared with never smokers, there was weakly increasing risk for increasing smoking behaviors, with the hazards ratios being 3.44, 4.91, and 5.18, respectively, for light, moderate, or heavy smokers, whereas among the individuals from families without the risk haplotype, the risks associated with smoking increased strongly with exposure, the hazards ratios being, respectively, 4.25, 9.17, and 11.89 for light, moderate, and heavy smokers. The never smoking carriers had a 4.71-fold higher risk than the never smoking individuals without known risk haplotypes. These results identify a region of chromosome 6q that increases risk for lung cancer and that confers particularly higher risks to never and light smokers.

Original languageEnglish (US)
Pages (from-to)2359-2367
Number of pages9
JournalCancer Research
Volume70
Issue number6
DOIs
StatePublished - Mar 15 2010

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Lung Neoplasms
Chromosomes
Light
Smoking
Haplotypes
Regression Analysis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Amos, C. I., Pinney, S. M., Li, Y., Kupert, E., Lee, J., De Andrade, M. A., ... Anderson, M. W. (2010). A susceptibility locus on chromosome 6q greatly increases lung cancer risk among light and never smokers. Cancer Research, 70(6), 2359-2367. https://doi.org/10.1158/0008-5472.CAN-09-3096

A susceptibility locus on chromosome 6q greatly increases lung cancer risk among light and never smokers. / Amos, Christopher I.; Pinney, Susan M.; Li, Yafang; Kupert, Elena; Lee, Juwon; De Andrade, Mariza A.; Yang, Ping; Schwartz, Ann G.; Fain, Pam R.; Gazdar, Adi; Minna, John; Wiest, Jonathan S.; Zeng, Dong; Rothschild, Henry; Mandal, Diptasri; You, Ming; Coons, Teresa; Gaba, Colette; Bailey-Wilson, Joan E.; Anderson, Marshall W.

In: Cancer Research, Vol. 70, No. 6, 15.03.2010, p. 2359-2367.

Research output: Contribution to journalArticle

Amos, CI, Pinney, SM, Li, Y, Kupert, E, Lee, J, De Andrade, MA, Yang, P, Schwartz, AG, Fain, PR, Gazdar, A, Minna, J, Wiest, JS, Zeng, D, Rothschild, H, Mandal, D, You, M, Coons, T, Gaba, C, Bailey-Wilson, JE & Anderson, MW 2010, 'A susceptibility locus on chromosome 6q greatly increases lung cancer risk among light and never smokers', Cancer Research, vol. 70, no. 6, pp. 2359-2367. https://doi.org/10.1158/0008-5472.CAN-09-3096
Amos, Christopher I. ; Pinney, Susan M. ; Li, Yafang ; Kupert, Elena ; Lee, Juwon ; De Andrade, Mariza A. ; Yang, Ping ; Schwartz, Ann G. ; Fain, Pam R. ; Gazdar, Adi ; Minna, John ; Wiest, Jonathan S. ; Zeng, Dong ; Rothschild, Henry ; Mandal, Diptasri ; You, Ming ; Coons, Teresa ; Gaba, Colette ; Bailey-Wilson, Joan E. ; Anderson, Marshall W. / A susceptibility locus on chromosome 6q greatly increases lung cancer risk among light and never smokers. In: Cancer Research. 2010 ; Vol. 70, No. 6. pp. 2359-2367.
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abstract = "Cigarette smoking is the major cause for lung cancer, but genetic factors also affect susceptibility. We studied families that included multiple relatives affected by lung cancer. Results from linkage analysis showed strong evidence that a region of chromosome 6q affects lung cancer risk. To characterize the effects that this region of chromosome 6q region has on lung cancer risk, we identified a haplotype that segregated with lung cancer. We then performed Cox regression analysis to estimate the differential effects that smoking behaviors have on lung cancer risk according to whether each individual carried a risk-associated haplotype or could not be classified and was assigned unknown haplotypic status. We divided smoking exposures into never smokers, light smokers (<20 pack-years), moderate smokers (20 to <40 pack-years), and heavy smokers (≥40 pack-years). Comparing results according to smoking behavior stratified by carrier status, compared with never smokers, there was weakly increasing risk for increasing smoking behaviors, with the hazards ratios being 3.44, 4.91, and 5.18, respectively, for light, moderate, or heavy smokers, whereas among the individuals from families without the risk haplotype, the risks associated with smoking increased strongly with exposure, the hazards ratios being, respectively, 4.25, 9.17, and 11.89 for light, moderate, and heavy smokers. The never smoking carriers had a 4.71-fold higher risk than the never smoking individuals without known risk haplotypes. These results identify a region of chromosome 6q that increases risk for lung cancer and that confers particularly higher risks to never and light smokers.",
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AU - Gazdar, Adi

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AU - Wiest, Jonathan S.

AU - Zeng, Dong

AU - Rothschild, Henry

AU - Mandal, Diptasri

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