Smoking May Turn on Lung Cancer Genes

Some Lung Cancer-Linked DNA Damage Permanent Even for Former Smokers

Medically Reviewed by Louise Chang, MD on August 29, 2007
From the WebMD Archives

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 smoking.

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 cancer.”

The analysis is published in the latest issue of the journal BMC Genomics.

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 considered safe.

“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.”

Show Sources

SOURCES: Lam, W.L. BMC Genomics, Aug. 29, 2007; open access, online journal. Wan L. Lam, PhD, senior researcher, department of Cancer Genetics and Developmental Biology, British Columbia Cancer Research Center, BC, Canada. Raj Chari, doctoral candidate, BC Cancer Research Center.

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