Molecular signature of smoking in human lung tissues.
Cigarette smoking is the leading risk factor for lung cancer. To identify genes deregulated by smoking and to distinguish gene expression changes that are reversible and persistent following smoking cessation, we carried out genome-wide gene expression profiling on nontumor lung tissue from 853 patients with lung cancer. Gene expression levels were compared between never and current smokers, and time-dependent changes in gene expression were studied in former smokers. A total of 3,223 transcripts were differentially expressed between smoking groups in the discovery set (n = 344, P < 1.29 × 10(-6)). A substantial number of smoking-induced genes also were validated in two replication sets (n = 285 and 224), and a gene expression signature of 599 transcripts consistently segregated never from current smokers across all three sets. The expression of the majority of these genes reverted to never-smoker levels following smoking cessation, although the time course of normalization differed widely among transcripts. Moreover, some genes showed very slow or no reversibility in expression, including SERPIND1, which was found to be the most consistent gene permanently altered by smoking in the three sets. Our findings therefore indicate that smoking deregulates many genes, many of which reverse to normal following smoking cessation. However, a subset of genes remains altered even decades following smoking cessation and may account, at least in part, for the residual risk of lung cancer among former smokers. Cancer Res; 72(15); 3753-63. ©2012 AACR.
Department of Molecular Medicine, Laval University, Québec, QC, Canada. yohan.bosse@crhl.ulaval.ca
Yohan
Y
Bossé
Dirkje S
DS
Postma
Don D
DD
Sin
Maxime
M
Lamontagne
Christian
C
Couture
Nathalie
N
Gaudreault
Philippe
P
Joubert
Vivien
V
Wong
Mark
M
Elliott
Maarten
M
van den Berge
Corry A
CA
Brandsma
Catherine
C
Tribouley
Vladislav
V
Malkov
Jeffrey A
JA
Tsou
Gregory J
GJ
Opiteck
James C
JC
Hogg
Andrew J
AJ
Sandford
Wim
W
Timens
Peter D
PD
Paré
Michel
M
Laviolette
D000368:Aged; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D006184:Habits; D006801:Humans; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012907:Smoking / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016540:Smoking Cessation; D013997:Time Factors; D054928:Validation Studies as Topic