NEW ORLEANS--A cytogenetic biomarker may be able to predict second cancers
in patients with Hodgkin's disease, Sara Strom, PhD, of M.D. Anderson Cancer
Center, reported at the American Society of Preventive Oncology (ASPO)
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 the
cytological manifestation of DNA double-strand breakage and rejoining between
two chromatids, Dr. Strom said.
They are possibly induced by agents that form DNA adducts or interfere
with DNA replication. The association between the initial events in cell
transformation and induction of DNA alterations makes SCEs a relevant indicator
The researchers evaluated SCEs and clinical and demographic characteristics
in 105 adult Hodgkin's disease patients treated from 1988 to 1992.
Sister chromatid exchanges were measured in 50 metaphases from pretreatment
blood samples. Patients with a break frequency in the highest quartile
were considered at high risk. Kaplan-Meier survival analysis was used to
predict second cancer risk.
During the follow-up period (mean of seven years), seven second cancers
occurred, including one case each of leukemia, non-Hodgkin's lymphoma,
breast cancer, metastatic tongue cancer, and melanoma, and two cases of
nonmela-noma skin cancer. The mean time between the primary cancer and
diagnosis of the second cancer was 4.6 years.
For patients with high SCEs, there was a significant difference in the
cumulative 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 associated
with increased risk, Dr. Strom said. Histology, stage, and treatment were
not associated with elevated risk. Two other cytogenetic biomarkers that
measure chromosome breaks, spontaneous and bleomycin-induced, were also
evaluated, but, she said, they did not seem to be useful in identifying
patients at high risk of developing secondary cancers.
"These findings suggest that an increased genetic susceptibility
may explain the occurrence of second cancers in some Hodgkin's disease
patients," she said.