Gene combination increases risk of lung cancer, particularly in light smokers, CAMH study finds

August 17, 2011

For immediate release - August 17, 2011 (Toronto) - Smokers with variations in two specific genes have a greater risk of smoking more cigarettes, becoming more dependent on nicotine and developing lung cancer, a new study from the Centre for Addiction and Mental Health (CAMH) shows.

The cancer risk from these two genes appears to be even higher in smokers who consume 20 or fewer cigarettes a day, according to the study published in the September issue of the Journal of the National Cancer Institute.

CAMH Scientist Dr. Rachel Tyndale and her team studied two genes: the nicotine metabolic gene (CYP2A6) and the nicotinic gene cluster (CHRNA5-A3-B3). These genes have been independently linked to smoking behaviours and lung cancer.

The new CAMH study looked at the effect of combined risks of both genes, possible gene interactions and the relative contribution of each gene on the number of cigarettes smoked, nicotine dependence and lung cancer risk in smokers.

"We found that the nicotine metabolic gene appears to have a larger influence on how many cigarettes people smoke each day, while the nicotinic gene cluster has a larger impact on the risk of lung cancer," said Dr. Tyndale. "The combined effect of having both high-risk gene variations more than doubled the odds of developing lung cancer."

The CAMH study included 417 lung cancer patients and a comparison group of 443 individuals with no cancer - all current or former smokers. Each individual was classified as having a low, intermediate or high risk of heavier cigarette smoking or developing cancer, depending on which combination of gene variants they had. The genetic profiles of study participants were linked to reports of cigarette smoking, a standard test of nicotine dependence, and lung cancer presence.

The genetic risk of lung cancer due to these two genes was highest among lighter smokers with both high-risk gene variations, compared to those with one or none of the high-risk gene variations.

"While heavier smoking increases the overall risk for lung cancer (as well as other health problems), our study looked specifically at the effects of these two genes on cancer risk, said Dr. Tyndale, who is also head of CAMH's Pharmacogenetics Lab. "We found the genetic risk from these two genes made a larger contribution among lighter smokers."

This finding is significant because most people tend to smoke less than they used to - in Ontario, adult smokers use an average of 13 cigarettes per day, according to the 2009 CAMH Monitor. Lighter smokers tend to perceive their risk as being lower, but if they have high-risk variants of these two genes, the genetic risk for lung cancer is high.

The percentage of individuals with these two genetic variations depends on ethnic background. Together, these variations influence an individual's response to nicotine and nitrosamines - a substance in tobacco smoke that is carcinogenic to the lungs. Dr. Tyndale's previous research on the nicotine metabolic gene has shown that people who are "fast metabolizers" break nicotine down more quickly. They have a harder time quitting and do not respond as well to nicotine replacement therapy as "slow metabolizers."

"This study indicates a significant risk for lung cancer is related to these two genes, and also suggests ways to intervene to reduce the risks," said Dr. Tyndale. "For instance, we are conducting a clinical trial to optimize cessation treatments based on genetic profiles, and fast metabolizers could be treated by using approaches that make them slow metabolizers."

Tobacco use is the primary cause of preventable disease and death in Canada and the USA. Smoking is the main cause of lung cancer, and also increases the risk of cancers of the colon, mouth, throat, pancreas, bladder and cervix.
-end-
For more information or to request an interview, contact: Sara Goldvine, CAMH Public Affairs at 647-567-7457 or sara_goldvine@camh.net

The Centre for Addiction and Mental Health (CAMH) is Canada's largest mental health and addiction teaching hospital, as well as one of the world's leading research centres in the area of addiction and mental health. CAMH combines clinical care, research, education, policy development and health promotion to help transform the lives of people affected by mental health and addiction issues.

CAMH is fully affiliated with the University of Toronto, and is a Pan American Health Organization/World Health Organization Collaborating Centre.

For more information on CAMH, please visit our website: http://www.camh.net/

Centre for Addiction and Mental Health

Related Lung Cancer Articles from Brightsurf:

State-level lung cancer screening rates not aligned with lung cancer burden in the US
A new study reports that state-level lung cancer screening rates were not aligned with lung cancer burden.

The lung microbiome may affect lung cancer pathogenesis and prognosis
Enrichment of the lungs with oral commensal microbes was associated with advanced stage disease, worse prognosis, and tumor progression in patients with lung cancer, according to results from a study published in Cancer Discovery, a journal of the American Association for Cancer Research.

New analysis finds lung cancer screening reduces rates of lung cancer-specific death
Low-dose CT screening methods may prevent one death per 250 at-risk adults screened, according to a meta-analysis of eight randomized controlled clinical trials of lung cancer screening.

'Social smokers' face disproportionate risk of death from lung disease and lung cancer
'Social smokers' are more than twice as likely to die of lung disease and more than eight times as likely to die of lung cancer than non-smokers, according to research presented at the European Respiratory Society International Congress.

Lung cancer therapy may improve outcomes of metastatic brain cancer
A medication commonly used to treat non-small cell lung cancer that has spread, or metastasized, may have benefits for patients with metastatic brain cancers, suggests a new review and analysis led by researchers at St.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Lung transplant patients face elevated lung cancer risk
In an American Journal of Transplantation study, lung cancer risk was increased after lung transplantation, especially in the native (non-transplanted) lung of single lung transplant recipients.

Proposed cancer treatment may boost lung cancer stem cells, study warns
Epigenetic therapies -- targeting enzymes that alter what genes are turned on or off in a cell -- are of growing interest in the cancer field as a way of making a cancer less aggressive or less malignant.

Are you at risk for lung cancer?
This question isn't only for people who've smoked a lot.

Read More: Lung Cancer News and Lung Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.