Mutagen sensitivity as an indicator of soft tissue sarcoma risk

The etiology of soft tissue sarcoma is poorly understood. Exposure to envir onmental chemicals may play a role, but the data are not clear. We compared a group of soft tissue sarcoma patients with healthy controls to determine whether the mutagen sensitivity assay, a simple chromosome aberration assa y using the radiomimetic bleomycin, might be useful to identify patients at risk for soft tissue sarcoma. Patients with a diagnosis of soft tissue sar coma at Memorial Sloan-Kettering's outpatient clinic signed informed consen t and donated 30 ml of blood. Controls were selected from the general popul ation of Connecticut by random digit dialing. Unrepaired DNA damage was ass essed for 100 metaphase spreads for each individual, with the number of bre aks in chromatids being counted as breaks per cell (b/c). The 20 cases with soft tissue sarcoma had 1.03 mean b/c and the controls had 0.88 b/c (P = 0 .16). Patients with soft tissue sarcoma were 5.7 times more likely to be mu tagen sensitive than controls (P = 0.01), as determined after dividing subj ects into sensitive or not sensitive groups based on the median b/c among c ontrols. As mutagen sensitivity has been shown to be associated with a numb er of cancers and appears to reflect genetic susceptibility, this assay may be an appropriate biomarker for radiation sensitivity or it may be a marke r of susceptibility to soft tissue sarcoma. Larger studies should be undert aken to assess these possibilities. (C) 2001 Wiley-Liss, Inc.