MUTAGEN SENSITIVITY AS A RISK FACTOR FOR 2ND MALIGNANT-TUMORS FOLLOWING MALIGNANCIES OF THE UPPER AERODIGESTIVE TRACT

Background: Second malignant tumors in patients successfully treated f or an initial cancer of the upper aerodigestive tract are an important cause of morbidity and mortality. Biologic markers capable of identif ying high-risk subgroups of patients who could be targeted for intensi ve clinical surveillance, therefore, have immense therapeutic and prog nostic relevance, We previously demonstrated in a pilot study of 84 pa tients with cancers of the upper aerodigestive tract that mutagen sens itivity was a significant predictor of risk of developing second malig nant tumors. Purpose: We extended the study to include 278 patients di agnosed with previously untreated cancers of the upper aerodigestive t ract from 1987 to August 1993. Methods: For each patient, base-line (p retreatment) mutagen sensitivity was measured in vitro in 50 metaphase s established from peripheral lymphocyte cultures. Patients with an av erage of more than 1 chromosomal break/cell were deemed mutagen hypers ensitive. Cox proportional hazards analysis was used to predict the ri sk of developing second malignant turners associated with mutagen sens itivity. Results: Overall, 44% of the case group exhibited mutagen hyp ersensitivity. There mere no differences in the distribution of mutage n hypersensitivity by site, sex, stage of disease, or smoking status. There were 17 synchronous and 11 metachronous cancers, of which 15 (54 %) were smoking-related malignancies. Sixteen (13.1%) of the mutagen-s ensitive patients developed second malignant tumors, compared with 12 (7.7%) of the nonsensitive patients. The mean break/cell value (+/-SD) for patients developing second malignant turners was 1.17 (+/-0.54), compared with 0.98 (+/-0.44) for patients with only one cancer (P =.04 ). Mutagen hypersensitivity conferred a relative risk of 2.67 (95% con fidence interval = 1.22-5.79) of developing second malignant tumors. C onclusions: Mutagen hypersensitivity increases the risk of developing second malignant tumors. Implications: Future research should focus on the molecular mechanisms underlying mutagen sensitivity.