Researchers in a large, multi-institutional study have found one gene variant that is linked to an increased risk of lung cancer.

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 variations—known as single nucleotide polymorphisms, or SNPs for short—between 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 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 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.

The research was funded by the National Institutes of Health, M.D. Anderson Cancer Center, Flight Attendants Medical Research Institute, Cancer Research UK, NCRN, HEAL, Sanofi-Aventis, and Allan J. Lerner Fund.

Authors on the paper are Christopher Amos, Xifeng Wu, Ivan Gorlov, Jian Gu, Qiong Dong, Qing Zhang, Xiangjun Gu, Wei Vivien Chen, Sanjay Shete, Gordon Mills and Margaret Spitz of U.T. M.D. Anderson Cancer Center, Houston, Texas; Peter Broderick, Jayaram Vijayakrishnan, Kate Sullivan, Athena Matakidou, Yufei Wang, and Richard Houlston of Institute of Cancer Research, UK; Timothy Eisen of Cambridge, UK; and Ya-Yu Tsai and Doheny of Hopkins.

The study will be published in the April 3 issue of Nature Genetics.

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