Smoking may change type of lymphoma into more lethal form of cancer

A Northwestern University investigator has hypothesized that smoking may play a dual role in the development of a cancer of the lymph glands called follicular lymphoma -- first causing it to develop and then transforming it into diffuse large cell lymphoma, an aggressive cancer generally associated with a poor prognosis.

Cancer researcher Ronald Gartenhaus, M.D., has been studying possible links between tobacco smoking and the genetic mutations associated with the transformation of follicular lymphoma, for which he recently received a $300,000 grant from the Flight Attendant Medical Research Institute. Gartenhaus is associate professor of medicine at The Feinberg School of Medicine and a researcher at The Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

More than 50,000 new cases of lymphoma were reported in 2001 -- a significant increase over the past 20 years even when HIV-related lymphomas are excluded. A small portion of the increased incidence of lymphomas has been attributed to exposure to chemical carcinogens such as herbicides and pesticides as well as to radiation. Now, smoking -- long known to cause cancer of the lung and other organs -- has been implicated in the development of a hematologic malignancy.

While this subset of lymphomas usually follows an indolent clinical course, a significant percentage transform into an aggressive large cell lymphoma with poor prognosis, Gartenhaus said. The vast majority of cases of follicular lymphoma have rearrangement of the Bcl-2 oncogene. The cases of follicular lymphoma that transform into diffuse large cell lymphoma have additional genetic alterations, particularly, mutations of the p53 tumor suppressor gene.

Research by others has shown that exposure to the aromatic hydrocarbons found in tobacco smoke causes distinct mutations in the p53 tumor suppressor gene.

One of p53's major roles is to arrest cells that have sustained DNA damage from proceeding into the p

Contact: Elizabeth Crown
Northwestern University

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