Cigarette smoking shown to affect transformation of low grade lymphomas into more deadly form of the disease
Cigarette smoking has long been known to cause cancer of the lung, as well as some cancers of the colon, breast and other organs. Now, researchers at the University of Maryland Marlene and Stewart Greenebaum Cancer Center (UMGCC) have found that smoking may play a role in the transformation of low grade lymphomas into a more lethal form of the disease by affecting the body’s ability to repair genetic mutations.
UMGCC researchers report finding a link between cigarette smoking and molecular changes that contribute to the transformation of some low grade lymphomas -- follicular lymphoma and chronic lymphocytic lymphoma -- into diffuse large cell lymphoma, a much more aggressive and difficult-to-treat type of lymph gland cancer.
The researchers analyzed tissue samples from 50 patients with transformed lymphomas. They looked for the presence of two specific proteins associated with repair of genetic mutations, HMLH1 or HMSH2. If one or both of these proteins is missing or damaged, the individual has what is known as a DNA mismatch repair defect.
“We wanted to examine whether there was an association between smoking
and the loss of either one of the two key mismatch repair proteins in transformed
lymphomas,” said study author Ronald
B. Gartenhaus, M.D., associate professor of medicine at the University of
Maryland School of Medicine and a researcher in the Molecular
and Structural Biology Program at the University of Maryland Marlene and
Stewart Greenebaum Cancer Center (UMGCC).
While the connection between smoking and cancer is well established, and studies have shown an increased incidence of DNA mismatch repair defects in patients with transformed lymphomas, this is the first evidence linking smoking in the transformation process.
Dr. Gartenhaus and his team found that, in fact, smokers had more than a two-fold increased relative risk over nonsmokers of having a DNA mismatch repair defect.
“These data suggest the need for a large, multi-institutional study with large numbers of patients in order to clarify the role of smoking and the transformation process in low grade lymphomas,” said Dr. Gartenhaus.
More than 50,000 new cases of lymphoma were reported in 2005. Approximately 50 percent of low grade lymphomas eventually transform into the more deadly diffuse large cell lymphoma.
The study also examined the presence of mutations of the p53 tumor suppressor gene. Although implicated in the lymphoma transformation process, p53 mutations did not correlate significantly with smoking.