Smoking and genetics

Compared to other lung cancer patients, smokers have 10 times more genetic damage in their tumors.

Lung cancer patients with a history of smoking have 10 times more genetic mutations in their tumors than those with the disease who have never smoked, according to a new study from Washington University School of Medicine.

“None of us were surprised that the genomes of smokers had more mutations than the genomes of never-smokers with lung cancer,” says senior author Richard K. Wilson, PhD, director of the university’s Genome Institute. “But it was surprising to see 10-fold more mutations. It does reinforce the old message — don’t smoke.”

The study appeared online Sept. 13 in the journal Cell.

Overall, the analysis identified about 3,700 mutations across all 17 patients with non-small cell lung cancer. Twelve patients had a history of smoking and five did not. In each patient who never smoked, the researchers found at least one mutated gene that can be targeted with drugs currently on the market for other diseases or available through clinical trials. Across all patients, they identified 54 mutated genes already associated with existing drugs.

Lung cancer patients with a history of smoking have 10 times more genetic mutations in their tumors than those with the disease who have never smoked.

“Whether these drugs will actually work in patients with these DNA alterations still needs to be studied,” says first author Ramaswamy Govindan, MD, an oncologist at the Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine. “But papers like this open up the landscape to understand what’s happening. Now we need to drill deeper to understand how these mutations cause and promote cancer, and how they can be targeted for therapy.”

Lung cancer is divided into two types — small cell and non-small cell, the latter accounting for about 85 percent of all cases. Within non-small cell lung cancer are three further classifications. This current analysis included two: sixteen patients had adenocarcinoma; one had large-cell carcinoma.

Govindan and Wilson also were involved in a larger genomic study of 178 patients with the third type, squamous cell carcinoma, recently reported in Nature. That study was part of The Cancer Genome Atlas project, a national effort to describe the genetics of common cancers. According to Govindan, research is moving toward clinical trials that will focus on the specific molecular biology of a patient’s cancer.

Based on this emerging body of genetic research demonstrating common mutations across disparate cancer types, Wilson speculates that the field may reach a point where doctors can label and treat a tumor based on the genes that are mutated rather than the affected organ.

NIH NHGRI US4 HG003079