Smoking May Turn on Lung Cancer Genes
Some Lung Cancer-Linked DNA Damage Permanent Even for Former Smokers
Aug. 29, 2007 -- Smoking is by far the biggest cause of lung cancer, but
about half of new cancers occur among people who have given up tobacco. Now new
genetic research may help explain why former smokers remain at risk.
A history of heavy smoking was found to switch on genes that may increase
susceptibility to lung cancer and switch off genes that fight the cancer, the
genetic analysis shows.
Much of the genetic damage caused by smoking was reversible when people
kicked the habit, but some DNA repair genes were irreversibly affected by
Since it is not clear how much smoking is needed to cause this irreversible
effect, the public health message from the research is a familiar one.
“If you don’t smoke, don’t start,” researcher Wan L. Lam, PhD, tells
WebMD. “And if you do smoke, quit as soon as possible because you may
still be able to avoid these irreversible genetic changes that can lead to lung
The analysis is published in the latest issue of the journal BMC
Smoking, Genes, and Lung Cancer
Wan and colleagues from the British Columbia Cancer Research Centre employed
a novel research technique known as serial analysis of gene expression (SAGE)
to identify important genetic changes in smokers compared with nonsmokers.
Theirs is the largest human SAGE study reported to date, involving analysis
of lung samples from four never smokers, 12 former smokers, and eight current
smokers over 45 years old.
The current and former smokers in the study all had smoked a minimum of a
pack of cigarettes a day for at least three decades. A former smoker had
stopped for a year or longer.
“These were heavy smokers or people who had been heavy smokers,” study
co-author Raj Chari tells WebMD. “But some of the former smokers had not smoked
for 20 years.”
Of the roughly 600 genes that were studied among the current and former
smokers and the never smokers, about a third were found to be reversible and a
third irreversible, Chari says.
The researches identified several genes not previously associated with
smoking that were switched on in active smokers, including the CABYR gene,
which has previously been identified with brain tumors and sperm motility.
Smoking-related genetic changes associated with the metabolism of foreign
compounds and mucus secretion were found to be reversible.
No Safe Smoking
It is not known if smoking less than a pack of cigarettes a day or smoking
for just a few years leads to the irreversible genetic damage seen in the lung
samples from the heavy smokers in the study.
But the researchers agree that no level of cigarette smoking can be
“We don’t want to alarm people unnecessarily and have them think that if
they smoked for just a few years they are at risk, or make people think that it
is ever too late to stop,” Chari says.
“We don’t know what the cutoff is for irreversible DNA damage. But even
smokers who have smoked for decades can benefit from stopping.”