A susceptibility locus on chromosome 6q greatly increases lung cancer risk among light and never smokers.
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.
Amos
Christopher I
CI
Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, Texas 77005, USA. camos@mdanderson.org
Pinney
Susan M
SM
Li
Yafang
Y
Kupert
Elena
E
Lee
Juwon
J
de Andrade
Mariza A
MA
Yang
Ping
P
Schwartz
Ann G
AG
Fain
Pam R
PR
Gazdar
Adi
A
Minna
John
J
Wiest
Jonathan S
JS
Zeng
Dong
D
Rothschild
Henry
H
Mandal
Diptasri
D
You
Ming
M
Coons
Teresa
T
Gaba
Colette
C
Bailey-Wilson
Joan E
JE
Anderson
Marshall W
MW
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*