Scientists at Johns Hopkins, as part of a large, multi-institutional study, have found one gene variant that is associated with an increased risk of lung cancer. The study would be reported in the April 3 issue of Nature Genetics.

The research team collected DNA from 1,154 smokers who have lung cancer and 1,137 smokers without lung cancer. Each DNA sample was analyzed at more than 300,000 points, looking for variationsknown as single nucleotide polymorphisms, or SNPs for shortbetween those with cancer and those without. They then analyzed the top 10 SNPs in an additional 5,075 DNA samples from smokers with and without lung cancer.

Two of the 10 SNPs were consistently linked to 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 observed that the same two SNPs also are weakly linked to smoking behavior.

The power of genome-wide analysis is to look at a number of markers and a number of 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.


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