A susceptibility locus on chromosome 6q greatly increases lung cancer risk among light and never smokers. Cancer Res 2010 Mar 15;70(6):2359-67
Date
03/11/2010Pubmed ID
20215501Pubmed Central ID
PMC2855643DOI
10.1158/0008-5472.CAN-09-3096Scopus ID
2-s2.0-77950241825 (requires institutional sign-in at Scopus site) 52 CitationsAbstract
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 (>or=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.
Author List
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 MWMESH terms used to index this publication - Major topics in bold
Chromosomes, Human, Pair 6Female
Genetic Linkage
Genetic Predisposition to Disease
Haplotypes
Humans
Lung Neoplasms
Male
Smoking
