Impact of smoking cessation on global gene expression in the bronchial epithelium of chronic smokers.
Cigarette smoke is the major cause of lung cancer and can interact in complex ways with drugs for lung cancer prevention or therapy. Molecular genetic research promises to elucidate the biological mechanisms underlying divergent drug effects in smokers versus nonsmokers and to help in developing new approaches for controlling lung cancer. The present study compared global gene expression profiles (determined via Affymetrix microarray measurements in bronchial epithelial cells) between chronic smokers, former smokers, and never smokers. Smoking effects on global gene expression were determined from a combined analysis of three independent data sets. Differential expression between current and never smokers occurred in 591 of 13,902 measured genes (P < 0.01 and >2-fold change; pooled data)--a profound effect. In contrast, differential expression between current and former smokers occurred in only 145 of the measured genes (P < 0.01 and >2-fold change; pooled data). Nine of these 145 genes showed consistent and significant changes in each of the three data sets (P < 0.01 and >2-fold change), with eight being down-regulated in former smokers. Seven of the eight down-regulated genes, including CYP1B1 and three AKR genes, influence the metabolism of carcinogens and/or therapeutic/chemopreventive agents. Our data comparing former and current smokers allowed us to pinpoint the genes involved in smoking-drug interactions in lung cancer prevention and therapy. These findings have important implications for developing new targeted and dosing approaches for prevention and therapy in the lung and other sites, highlighting the importance of monitoring smoking status in patients receiving oncologic drug interventions.
Zhang
Li
L
Department of Bioinformatics. The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. Lzhangli@mdanderson.org
Lee
J Jack
JJ
Tang
Hongli
H
Fan
You-Hong
YH
Xiao
Lianchun
L
Ren
Hening
H
Kurie
Jonathan
J
Morice
Rodolfo C
RC
Hong
Waun Ki
WK
Mao
Li
L
D000368:Aged; D001980:Bronchi / Q000378:metabolism* / Q000473:pathology; D002908:Chronic Disease; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000473:pathology; D012907:Smoking / Q000009:adverse effects / Q000235:genetics / Q000378:metabolism; D016540:Smoking Cessation; D013997:Time Factors; D014029:Tobacco Use Disorder / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000534:rehabilitation*