title: A susceptibility locus on chromosome 6q greatly increases lung cancer risk among light and never smokers.
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 (>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.
authors.affiliation: Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, Texas 77005, USA. camos@mdanderson.org
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Amos
authors.forename: Susan M
authors.initials: SM
authors.lastname: Pinney
authors.forename: Yafang
authors.initials: Y
authors.lastname: Li
authors.forename: Elena
authors.initials: E
authors.lastname: Kupert
authors.forename: Juwon
authors.initials: J
authors.lastname: Lee
authors.forename: Mariza A
authors.initials: MA
authors.lastname: de Andrade
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.forename: Ann G
authors.initials: AG
authors.lastname: Schwartz
authors.forename: Pam R
authors.initials: PR
authors.lastname: Fain
authors.forename: Adi
authors.initials: A
authors.lastname: Gazdar
authors.forename: John
authors.initials: J
authors.lastname: Minna
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Wiest
authors.forename: Dong
authors.initials: D
authors.lastname: Zeng
authors.forename: Henry
authors.initials: H
authors.lastname: Rothschild
authors.forename: Diptasri
authors.initials: D
authors.lastname: Mandal
authors.forename: Ming
authors.initials: M
authors.lastname: You
authors.forename: Teresa
authors.initials: T
authors.lastname: Coons
authors.forename: Colette
authors.initials: C
authors.lastname: Gaba
authors.forename: Joan E
authors.initials: JE
authors.lastname: Bailey-Wilson
authors.forename: Marshall W
authors.initials: MW
authors.lastname: Anderson
mesh_terms: D002896:Chromosomes, Human, Pair 6; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology / Q000235:genetics*; D008297:Male; D012907:Smoking / Q000009:adverse effects / Q000235:genetics*