Genetic Instability And Development Of Second Primary Tumors After Hodgkin's Disease

Researchers at The University of Texas M. D. Anderson Cancer Center have discovered that genetic instability may help predict which subset of patients is at greatest risk for second cancers--which, in turn, could pose important implications for their treatment and long-term follow-up.

"It is particularly devastating for young adults to be hit with Hodgkin's disease, do well, and then face another cancer ten to 20 years down the line," said Rand El-Zein, M.D., Ph.D., an assistant professor of epidemiology at M. D. Anderson. "Cytogenetic and chromosomal abnormalities have already been validated as such as markers of cancer risk. We wanted to find out if there are genetic markers that can serve as predictors of second primary tumors."

The study analyzed chromosomal aberrations in lymphocytes collected from 252 adult Hodgkin's disease patients before they began treatment between 1986 and 1992. Their analysis focused on the number of chromatid breaks during 100 complete cell metaphases. Researchers found a strong correlation between the number of breaks and the likelihood of developing a second cancer.

At a follow-up of approximately 13 years, 27 patients, or 11 percent, developed second primary cancers: five solid tumors, four leukemia, eleven skin cancers, and seven lymphomas. These patients had significantly higher levels of total breaks than patients who remained cancer-free. The 25 percent of patients with the highest number of breaks were almost two-and-a-half times more likely to develop second cancers.

"We believe that these chromosomal aberrations explain why some patients develop second primary cancers and some don't," said El-Zein. She also noted that this information could potentially be useful in tailoring treatment regimens and follow-up surveillance.

"For a patient with a higher level of genetic instability, you might want to give them a less toxic regimen, or spread out the treatments more, or give them some kind of agent to boost their genetic repair mechanisms," said El-Zein. "Or you might want to do closer surveillance in the years after treatment."

The research team is now looking at other potential predictors of second cancer risk, such as polymorphisms in the DNA repair genes, and plans to analyze samples taken from the same patients over time. Information about each patient's treatment regimen also will help them determine if there is a correlation between genetic instability and toxicity from the treatment.

"Being able to predict the likelihood of a second cancer has great potential to be helpful not only for Hodgkin's disease survivors, but for survivors of any cancer that is associated with later risk of a secondary cancer," El-Zein said.