Cytogenetic Marker May Predict Second Cancer After Hodgkin's Disease

NEW ORLEANS--A cytogenetic biomarker may be able to predict second cancersin patients with Hodgkin's disease, Sara Strom, PhD, of M.D. Anderson CancerCenter, reported at the American Society of Preventive Oncology (ASPO)annual meeting.

She presented data showing a high relative risk of second cancers (11.6)associated with high levels of sister chromatid exchanges (SCEs).

Sister chromatid exchanges are thecytological manifestation of DNA double-strand breakage and rejoining betweentwo chromatids, Dr. Strom said.

They are possibly induced by agents that form DNA adducts or interferewith DNA replication. The association between the initial events in celltransformation and induction of DNA alterations makes SCEs a relevant indicatorof carcinogenesis.

The researchers evaluated SCEs and clinical and demographic characteristicsin 105 adult Hodgkin's disease patients treated from 1988 to 1992.

Sister chromatid exchanges were measured in 50 metaphases from pretreatmentblood samples. Patients with a break frequency in the highest quartilewere considered at high risk. Kaplan-Meier survival analysis was used topredict second cancer risk.

During the follow-up period (mean of seven years), seven second cancersoccurred, including one case each of leukemia, non-Hodgkin's lymphoma,breast cancer, metastatic tongue cancer, and melanoma, and two cases ofnonmela-noma skin cancer. The mean time between the primary cancer anddiagnosis of the second cancer was 4.6 years.

For patients with high SCEs, there was a significant difference in thecumulative probability of developing a second cancer in the high-risk group,compared with the low-risk group.

Among all the variables analyzed, only older age at diagnosis was associatedwith increased risk, Dr. Strom said. Histology, stage, and treatment werenot associated with elevated risk. Two other cytogenetic biomarkers thatmeasure chromosome breaks, spontaneous and bleomycin-induced, were alsoevaluated, but, she said, they did not seem to be useful in identifyingpatients at high risk of developing secondary cancers.

"These findings suggest that an increased genetic susceptibilitymay explain the occurrence of second cancers in some Hodgkin's diseasepatients," she said.