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Researchers shed light on what triggers tumors in lung cancer

October 12, 2011 — For decades cigarette smoking has been considered a risk factor for lung cancer, but exactly how tobacco use causes tumors to grow in the lungs is not fully understood.

A new study led by Harvard School of Public Health (HSPH) researchers used a genome-wide analysis to assess abnormalities in the DNA structure of 264 nonsmallcell-lung cancer (NSCLC) tumors from Boston patients and compared the findings to the average number of cigarette packs smoked per year by the patients. The study appeared in the September 27, 2011, print edition of Proceedings of the National Academy of Sciences (PNAS).

The researchers found heavy smokers—those who smoked 60 or more packs per year—have significantly more defects in their DNA than those who smoked 60 or fewer packs annually and non-smokers.

“This is a finding never described before in relation to smoking,” said senior author David Christiani, Elkan Blout Professor of Environmental Genetics at HSPH. While scientists have known that DNA alterations occurred in lung cancer tumors, “this carefully assembled molecular epidemiology study had the additional exposure information to make the connection [to smoking as the cause],” Christiani said.

About 85% of lung cancer is NSCLC, the second most common cancer and the leading cause of cancer-related death in the United States, according to the paper.

The researchers, led by Yen-Tsung Huang, a physician and doctoral candidate in epidemiology and biostatistics, Xihong Lin, professor of biostatistics, Christiani, and colleagues at the Massachusetts General Hospital (MGH), Dana Farber Cancer Institute, Brigham and Women’s Hospital, and Norway’s National Institute of Occupational Health, compared lung tumor cells from MGH patients to an independent sample from Norway.

The authors measured the DNA copy numbers to identify structural variations in the tumor cells. For example, the chromosome that normally has sections in order as A-B-C-D might instead have sections A-B-C-C-D (a duplication of “C”) or A-B-D (a deletion of “C”). The authors theorized that cigarette smoking serves as an environmental stressor on the cells and contributes to genome instability, generating DNA changes in certain chromosomes.

The new findings one day may have implications for potential treatment targets for lung cancer patients, Christiani said.

The study was supported by funding from the National Institutes of Health, the Raymond P. Lavietes Foundation,  and the Norwegian Cancer Society.

–Marge Dwyer

photo: iStockphoto.com

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Christiani MGH/HSPH Lung Cancer Study

“Where DNA Meets Daily Life” (Harvard Public Health Review, Fall 2010)