Genetics and Health

Smokers and ex-smokers - lung cancer gene identified

by Elaine on April 4th, 2008

A research team comprising scientists from MD Anderson, Johns Hopkins University and the Insitutute for Cancer Research and the University of Cambridge, UK have identified two inherited genetic variations (SNPs) on chromosome 15 associated with increased risk of lung cancer for smokers and former smokers. Individuals who have ever smoked and who have one or two copies of either of these SNPs have increased risks ranging from 28% to 81% of developing lung cancer.

The findings are a major step forward in identifying those at high risk for non-small cell lung cancer and for understanding how smoking and genetic factors interact to cause the disease. The team’s findings might also provide support for a growing body of evidence suggesting that nicotine, long known as the prime addictive compound in cigarettes, might also play a direct causative role in the development of lung cancer.

The research team conducted a series of genome-wide association studies, first genotyping 317,498 different SNPs from 1,154 smokers who had lung cancer and 1,137 smokers without lung cancer. They then analyzed the top 10 SNPs in an additional cohort of Amercian patients and replicated the research in a cohort of 5,075 DNA samples from UK smokers with and without lung cancer and narrowed the SNPs down to two variations.

Two of the 10 SNPs were consistently associated with lung cancer risk and both of them are located in chromosome 15 inside a region that contains genes for the nicotinic acetylcholine receptor alpha subunits 3 and 5, which already are suspected to play a role in lung cancer progression.

The research team then wondered if these genetic associations relate to nicotine dependence, and found that the same two SNPs also are weakly associated with smoking behavior.

The genetic variations might help identify smokers at higher lung cancer risk who would be the best candidates for regular screening.

The study was predominantly undertaken on a Caucasian cohort to eliminate ethnic variation. A similar genome-wide study of African-American smokers is planned.

“The power of genome-wide analysis is to look at many markers and many samples at once, which can reveal weak genetic associations in complex diseases like lung cancer.”says Kimberly Doheny, Ph.D., assistant director of the Center for Inherited Disease Research at the McKusick-Nathans Institute of Genetic Medicine at Johns Hopkins.

Elaine Warburton www.geneticsandhealth.com

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POSTED IN: General Genetics and Health, Genetic Testing, Genetic risk, Personalized Medicine, SNPs, cancer, lung-cancer