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Researchers at Washington University in St. Louis, Missouri, recently found that patients with lung cancer who have a history of smoking have 10 times more genetic mutations in their tumors than patients who have never smoked.1

The study included an analysis of 17 patients with nonsmall cell lung cancer. Twelve of these patients had a history of smoking whereas the other 5 did not (1 patient was a light smoker). Specifically, investigators identified more than 3700 mutations, with an average frequency of mutations found to be more than 10 times higher in smokers than in people who had never smoked. New alterations in genes were identified, along with DACH1 (Dachshund homolog 1 [Drosophila]), CFTR (cystic fibrosis transmembrane conductance regulator), RELN (reelin), ABCB5 (ATPbinding cassette, sub-family B (MDR/TAP), member 5), and HGF (hepatocyte growth factor [hepapoietin A; scatter factor]).

The authors noted that approximately 10% to 40% of patients with lung cancer report no prior history of smoking. The largest number of never-smokers is reported in Asia. Factors such as environmental exposures and genetic susceptibility are thought to influence lung cancer risk in this group.

“Overall, the number of point mutations in the lung cancer genome appears to be closely related to the patient's tobacco smoking status, and the landscape of the former light-smoker genome suggests a possible doseresponse relationship between the amount and duration of tobacco smoke exposure and the extent of mutational burden,” the authors summarize in their article.

In the participants who had never smoked, investigators found at least 1 mutation that could be targeted with drugs already on the market for other diseases or that are available through clinical trials. They also found 54 mutated genes in all the patients that are associated with existing drugs.

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Ramaswamy Govindan, MD, the study's first author and a professor in the oncology division in the department of medicine at Washington University, says that it is not yet known whether existing drugs will work in these patients, but that the study should lead to more research on how the mutations cause and promote cancer, and whether they can be targeted.

Dr. Govindan and Richard Wilson, PhD, director of the Genome Institute at Washington University, also have been involved in a large genomic study of 178 patients with squamous cell carcinoma, 1 of 3 subtypes of nonsmall cell lung cancer. The other 2 subtypes were analyzed in the current study, which included 16 patients with adenocarcinoma and 1 patient with large cell carcinoma.

Within the next year, Drs. Govindan, Wilson, and their colleagues will have studied nearly 1000 genomes of patients with lung cancer as part of The Cancer Genome Atlas, with the goal of developing clinical trials that focus on the specific molecular biology of patients' cancers.

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  2. More Research Is on the Way
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