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Genetic variations raise lung cancer risk for smokers and ex-smokers
Date:4/2/2008

ry by a single DNA chemical building block or nucleotide. Individuals who have ever smoked and who have one or two copies of either of these SNPs have increased risks ranging from 28 percent to 81 percent of developing lung cancer, the researchers found.

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.

There are five genes in the area of chromosome 15 where the two risk-raising SNPs were identified, Amos explained. Of those, three are nicotine acetylcholine receptor genes that encode proteins that serve as docking sites to which nicotine can bind.

"Once bound, these receptors set in motion a cascade of signals. Nicotine is known to activate cell proliferation, new blood vessel development and growth factors while upregulating several signaling pathways. If these are indeed causal genes, that will be of great interest," Amos said.

Another potential causative gene in the area is one that encodes a component of the proteasome, which degrades other proteins. The function of the fifth gene has yet to be identified.

Further studies with additional SNPs in African-American populations who show different SNP patterns may help to define which of these five genes causes lung cancer. Collaborations with both M. D. Anderson's Lung SPORE and the Kleberg Center for Molecular Markers will evaluate whether these SNPs influence expression of any of these five genes in lung cancers and normal lung tissue, Amos said.

Lung cancer causes more deaths than any other cancer, killing more than 160,000 Americans annually and millions worldwide. Non-small cell lung cancer makes up 80 percent of all lung cancer cases.

Amos and senior co-author Margaret Spitz, M.D., chair of M. D. Anderson's Department of Epidemiology, conceived the study, which
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Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert  

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