Mutagen sensitivity in patients with head and neck cancers: a biologic marker for risk of multiple primary malignancies. Eighty-four patients with head and neck cancers were evaluated for in vitro sensitivity to mutagens and then followed longitudinally for development of multiple primary malignancies. We assessed mutagen sensitivity by exposing lymphocytes to bleomycin in vitro and quantitating the bleomycin-induced chromosomal breaks per cell. The mutagen-hypersensitive patients, ie, those who expressed greater than 1.0 break per cell, were significantly more likely to develop multiple primary cancers than were patients who were less sensitive (less than or equal to 1.0 break per cell) (relative risk = 4.4; 95% confidence limits = 1.2, 15.8). This relationship was independent of age, sex, site, and treatment of first primary cancer and tobacco or alcohol exposures. Sensitivity to bleomycin-induced chromosomal damage serves as an indicator of genetic susceptibility to multiple primary malignancies in patients with head and neck cancers. 