Smokers With Lung Cancer Have Tenfold Genetic DamageFeatured Article
Main Category: Smoking / Quit Smoking
Also Included In: Lung Cancer; Genetics
Article Date: 17 Sep 2012 - 12:00 PDT
The tumors of smokers who develop lung cancer have ten times more genetic damage than those of never-smokers who develop the disease, according to a study published online in the journal Cell this week.
Senior author Richard K. Wilson is director of The Genome Institute at Washington University School of Medicine in St. Louis in the US. He says in a media statement that none of his team was surprised that the genomes of smokers with lung cancer had more mutations than the genomes of never-smokers with the disease:
"But it was surprising to see 10-fold more mutations. It does reinforce the old message - don't smoke," he adds.
Lung CancerThere are two main types of lung cancer: small cell and non-small cell (NSCLC), which accounts for about 85% of all cases.
Within non-small cell there are also three further classifications: adenocarcinomas (usually found in an outer area of the lung); squamous cell carcinomas (usually found in the center of the lung next to a bronchus or air tube); and large cell carcinomas (these can occur in any part of the lung and tend to grow and spread faster than the other two classes).
The StudyFor their study, Wilson and colleagues examined tissue from 17 patients: 16 with adenocarcinoma and one with large-cell carcinoma. 12 of the patients had a history of smoking, while the other five did not.
In their paper, the researchers describe how they carried out "whole-genome and transcriptome sequencing of tumor and adjacent normal tissue samples" from all 17 patients.
Across all 17 patients they identified just over 3,700 mutations, with an average mutation frequency more than 10-fold higher in the smokers compared to the never-smokers.
Available Drugs May Already Serve Against Some of the MutationsAcross all the patients, the researchers identified 54 mutations for which targeted drugs are already available. In each patient who had never smoked, there was at least one gene that can be targeted with available drugs.
However, the researchers can't say whether these will work on these mutations in lung cancer patients, as first author Ramaswamy Govindan, an oncologist who treats patients at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University, explains:
"Whether these drugs will actually work in patients with these DNA alterations still needs to be studied."
"But papers like this open up the landscape to understand what's happening. Now we need to drill deeper and do studies to understand how these mutations cause and promote cancer, and how they can be targeted for therapy," he adds.
The Cancer Genome Atlas ProjectWilson and Govindan are also part of The Cancer Genome Atlas project, which recently reported in Nature a larger genomic study of 178 patients with squamous cell carcinoma lung cancer.
Govindan says over the next 12 months or so the project will have studied nearly 1,000 genomes of patients with lung cancer. He says research is moving in the right direction, "toward future clinical trials that will focus on the specific molecular biology of the patient's cancer".
Shift from Organ-Based to Gene-Based View of CancerWilson says the emerging evidence from genetic research is starting to make scientists re-think cancer: many quite different cancers appear to share the same mutations.
He sees a day when doctors no longer talk about "lung cancer", for example, but about "EGFR cancer", after the mutated gene that drives the tumor growth. Mutations in the EGFR (epidermal growth factor receptor) gene have been found in lung, colon, breast, and other cancers.
Citing another example, Wilson says he has seen lung cancer patients with mutations in the same gene that is targeted by Herceptin, essentially a breast cancer drug.
"In the coming years, we hope to be treating cancer based more on the altered genetic make-up of the tumor than by the tissue of origin," he notes.
Written by Catharine Paddock PhD
Copyright: Medical News Today
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