Study says BC Cancer Agency research helps explain why
many former smokers still develop lung cancer

By:  Pamela Fayerman
Vancouver Sun
Sun Health Issues Reporter
pfayerman@png.canwest.com

BC CANCER AGENCY

A new BC Cancer Agency study serves as a sobering message why people should never start smoking in the first place, the study’s authors said Wednesday.

It may also help explain why so many former smokers still get lung cancer long after they quit.

In the first study of its kind, the researchers identified a number of genes that suffer irreversible damage from tobacco smoke, which helps explain why half of all those diagnosed with lung cancer are former, not current smokers.

“ Smoking is like playing Russian roulette and the longer one smokes, the more likely it is that there will be even more bullets in the gun,” study co- author Calum MacAulay said in an interview.

MacAulay, a biophysicist, a specialist in cancer imaging and one of six authors of the study published Wednesday in the online journal BMC Genomics, said it is unclear why some lifeor long- time smokers escape lung cancer. The study didn’t delve into that.

Scientists compared samples of cells scraped from the respiratory tracts of eight current smokers, 12 former smokers and four subjects who have never smoked.

Using a technique called serial analysis of gene expression ( SAGE) to help identify gene activity patterns, they identified at least 600 genes that are affected by smoking and found that while some genes return to normal after smokers quit, about 120 genes remain altered.

A former smoker was defined as someone who had stopped smoking for at least a year but in the study, former smokers had quit smoking an average of 11 years ago. The “ irreversible” changes to their genes have persisted.

“ The former smokers in this study have a long history of smoking ( a pack a day for 30 years or two packs a day for at least 15 years). Such irreversible damages are therefore what can happen if an individual continues to smoke heavily for a long time,” said Wan Lam, a molecular biologist in the agency’s department of cancer genetics and developmental biology.

“ The longer smokers smoke, the more likely it is that genes will be irreversibly damaged,” Lam said, adding that the study also found that there are certain genes associated with DNA repair that are “ irreversibly under- expressed” in people who have smoked or still do.

Michael MacDonald, a former smoker who is a line producer in the local film industry, said he’s not that surprised by the results.

“ I was a smoker for over 30 years,” MacDonald said, “ and although I quit cold turkey 10 or 11 years ago, I am not going to pretend I didn’t do permanent damage to my lungs and I’d be very surprised if I escaped deep harm.

“ But two or three months after I quit, I felt so much better and there’s no turning back,” he said.

“ People who smoke should realize they can’t push their luck. Studies like this are there to forewarn and forearm,” said MacDonald, who has enrolled himself in a lung- health study at the cancer agency.

MacDonald, who was not in the current study, said his brother, sisters and mother have all had brushes with cancer and his decision to quit smoking and then get involved in research was prompted by his family history.

He has already learned that he has a pre- malignant nodule on one lung, he said in an interview from Los Angeles, where he is attending business meetings.

Former and current smoking is said to account for 85 per cent of all lung cancer cases. Lung cancer is the most common cause of cancer- related death.

Lam said the next phase of the research will involve further study of the role of irreversible gene changes in lung cancer development.

“ We will do this by comparing the molecular changes present in the lung tumours from smokers versus non- smokers,” he said. “ And we will also identify which of the changes in the tumours are present in smoke- damaged lung tissue and absent in normal lungs.”

One of the more surprising findings in the study was that a gene called CABYR, which is involved in sperm motility, is more active in smokers than in former and non- smokers.

The researchers believe this may be because smoking creates an overabundance of mucus in the airways.

“ Over- expression” of CABYR is also found in a variety of brain tumours.

The study was funded with g r a n t s f rom Genome Canada/ Genome B. C., the Canadian institute of Health Research and the National Institute of Dental and Cranialfacial Research.