VANCOUVER, British Columbia -- For some genes involved in the development of lung cancer, smoking may be forever, according to researchers here.
VANCOUVER, British Columbia, Aug. 29 -- For some genes involved in the development of lung cancer, smoking may be forever, according to researchers here.
Smoking irreversibly activates some lung genes and down-regulates others, offering a possible explanation for the elevated lung cancer risk of former smokers, reported Raj Chari, Ph.D., of the British Columbia Cancer Agency, and colleagues, online in BMC Genomics.
They studied lung biopsy specimens from current, former, and nonsmokers and found that smoking induces specific changes in gene activity, some of which are permanent.
DNA repair genes are irreversibly damaged by smoking, which also turns off genes that protect against lung cancer. Down-regulated genes that regain normal function with smoking cessation are involved in xenobiotic functions, nucleotide metabolism, and mucus secretion.
"Expression levels of some of the genes related to tobacco smoking return to levels similar to never-smokers upon cessation of smoking, while expression of others appears to be permanently altered despite prolonged smoking cessation," the authors concluded. "These irreversible changes may account for the persistent lung cancer risk despite smoking cessation."
Recent gene microarray studies revealed differences in gene expression among current, former, and nonsmokers. The studies linked smoking's genetic effects to specific functions and showed that some smoking-induced changes are not reversed by smoking cessation.
Despite the recent findings, relatively little is known about genes involved in smoking-induced airway remodeling.
Dr. Chari and colleagues used serial analysis of gene expression (SAGE) to examine gene expression profiles in lung tissue. SAGE determines expression profiles by analyzing the types and concentration of short sequence tags. The investigators compared bronchial epithelial transcriptomes of current, former, and never smokers.
The study involved eight current smokers, 12 former smokers, and four never-smokers. Analysis of bronchial specimens from the participants resulted in 3,111,471 SAGE tags, representing 110,000 potentially unique transcripts. The investigators also identified 1,733 constitutively expressed genes in the transcriptomes of current, former, and never-smokers.
Further analysis revealed 609 SAGE transcript tags that were differentially expressed between current and never smokers. Chari and colleagues subsequently found that the tags classified current, former, and never smokers.
Additional comparisons of current, former, and never-smokers separated the tags and their associated genes into categories of reversible, partly reversible, and irreversible. Examples included:
These finding were validated using quantitative reverse transcriptase-polymerase chain reaction on a secondary cohort of nine current smokers, seven former smokers, and six never-smokers.
The identification of reversible changes in gene expression in response to smoking cessation may help guide future studies of polymorphisms, the authors stated. Genes and functions that do not revert to normal upon smoking cessation may provide insight into former smokers' ongoing risk of developing lung cancer.