Smoking Causes Irreversible Gene Damage

Main Category: Smoking / Quit Smoking
Also Included In: Cancer / Oncology;  Lung Cancer
Article Date: 31 Aug 2007 - 2:00 PDT

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BC Cancer Agency researchers, led by Drs. Stephen Lam and Wan Lam, have discovered new evidence that explains why former smokers are still susceptible to lung cancer after they have stopped smoking for many years.

Published today in the online journal BMC Genomics, the study shows that in former smokers, some genes associated with tobacco smoking return to levels similar to people who never smoked, while other genes appear to be permanently damaged.

"The study is important because it helps to explain why heavy smokers who have stopped smoking are still at risk of lung cancer," says Dr. Stephen Lam, one of the principal investigators and chair of the BC Cancer Agency's lung tumour group. "Fifty percent of patients with newly diagnosed lung cancer are now former smokers."

Using samples from the lungs of 24 current, former, and non-smokers, researchers created libraries using a technique called serial analysis of gene expression (SAGE), which helps to identify patterns of gene activity. They identified close to 600 genes that were differentially expressed between current and non-smokers. This is the largest human SAGE study reported to date.

Only about a fifth of the genes in a cell are switched on at any given time, but environmental factors such as smoking lead to changes in gene activity. Of the 600 genes identified, changes in almost one third of them are irreversible in former smokers. Specifically, some DNA repair genes are irreversibly damaged by smoking, and smoking also switched off genes that help combat lung cancer development. Nearly another third of the genes displayed changes that are reversible by stopping smoking.

"Further investigation into the genes and functions that do not revert to normal levels upon smoking cessation may provide us with new insight into the development of lung cancer," says Raj Chari, lead author of the study and graduate student at the BC Cancer Agency.

The researchers also identified a number of genes not previously associated with smoking, which are switched on in active smokers. One example is CABYR, which is involved in helping sperm to swim, and is also associated with brain tumours. The researchers also further investigated changes in genes involved in airway repair and regeneration, and within this group identified genes that fell into three categories following cessation of smoking: reversible (TFF3, CABYR), partially reversible (MUC5AC) and irreversible (GSK3B). These findings were tested against a second cohort of current, former and non-smokers.

It is estimated that more men and women will die from lung cancer than from prostate breast and colorectal cancer combined. In 2007, approximately 2,723 British Columbians will be diagnosed with lung cancer and 2,298 will die of it.

The BC Cancer Agency is currently enrolling people in a project called the Lung Health Study, which focuses on the early detection of lung and bronchial cancer, and the identification of new agents that may halt or slow the growth of abnormal cells in these organs. Former smokers between the ages of 45 and 74 who have smoked at least one package of cigarettes per day for 30 years are the primary target of the study.

Core support for research at the BC Cancer Agency is provided by the BC Cancer Foundation. This study was also funded by Genome Canada/ Genome BC and the National Cancer Institute (USA).

The BC Cancer Agency, an agency of the Provincial Health Services Authority, is committed to reducing the incidence of cancer, reducing the mortality from cancer, and improving the quality of life of those living with cancer. It provides a comprehensive cancer control program for the people of British Columbia by working with community partners to deliver a range of oncology services, including prevention, early detection, diagnosis and treatment, research, education, supportive care, rehabilitation and palliative care. The BC Cancer Foundation raises funds to support research and enhancements to patient care at the BC Cancer Agency.

http://www.bccancer.bc.ca

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