Chromosomal alterations in lung adenocarcinoma from smokers and nonsmokers

The etiology of lung tumors arising in nonsmokers remains unclear, Although mutations in the K-ras and p53 genes have been reported to be significantl y higher in smoking-related lung carcinomas, in the present study we perfor med a more comprehensive analysis in search of additional genetic changes b etween lung adenocarcinoma from tobacco- and non-tobacco-exposed patients. We selected a matched cohort of 18 lifetime nonsmoking and 27 smoking patie nts diagnosed with primary adenocarcinoma of the lung and searched for chro mosomal alterations in each tumor by testing normal and tumor tissue with 5 4 highly polymorphic microsatellite markers located on 28 different chromos omal arms. Allelic losses or gains at chromosomal arms 3p (37 versus 6%), 6 q (46 versus 12%), 9p (65 versus 22%), 16p (28 versus 0%), 17p (45 versus 1 1%), and 19p (58 versus 16%) were present significantly more often in adeno carcinomas from smokers than from nonsmokers. Chromosomal arms showing alle lic imbalance in lung tumors from nonsmokers were rare but occurred more of ten at 19q (22%), 12p (22%), and 9p (22%). The FAL (fractional allelic loss or gain) is defined as the percentage of chromosomal arm losses/gains amon g the total informative chromosomal arms. Tumors from smokers harbored high er levels of FAL (13 (48%) of 27 showed FAL greater than or equal to 0.3) c ompared with the lung tumors from the nonsmoker patients (2 (11%) of 18 sho wed FAL greater than or equal to 0.3; P = 0.02; odds ratio, 0.13; 95% confi dence interval, 0.01-0.79). Our data demonstrate that widespread chromosoma l abnormalities are frequent in lung adenocarcinoma from smokers, whereas t hese abnormalities are infrequent in such tumors arising in nonsmokers. The se observations support the notion that lung cancers in nonsmokers arise th rough genetic alterations distinct from the common events observed in tumor s from smokers.