DNA-REPAIR AND MUTAGEN SENSITIVITY IN PATIENTS WITH TRIPLE PRIMARY CANCERS

The purpose of this study was to measure DNA repair capacity and mutag en sensitivity in patients who have had three or more primary forms of cancer, It was hypothesized that,, if abnormalities in DNA repair and mutagen sensitivity mere cancer susceptibility factors, such findings mould be seen with regularity in individuals with multiple primary ca ncers. DNA repair capacity was measured by determining repair of UV-ir radiated plasmid DNA (pCMVCAT) transfected into peripheral blood lymph ocytes, Results from 18 patients and a like number of age-and sex-matc hed controls demonstrated a significant difference in DNA repair capac ity (P < 0.0001; odds ratio = 14). Mutagen sensitivity was measured by determining the mean number of chromatid breaks per cell after in vit ro exposure to either bleomycin or 4-nitroquinoline-1-oxide. The diffe rence in mean bleomycin- or 4-nitroquinoline-1-oxide-induced mutagen s ensitivity between cases and controls was not statistically significan t, Fourteen of the 18 patients had positive family histories of cancer ; in 10, the history was compatible with cancer susceptibility syndrom es, Although the numbers were small, there was no suggestion in this s tudy that treatment or the presence of cancer was the cause of the DNA repair abnormalities encountered, These findings support the concept of diminished DNA repair capacity as an underlying feature in the deve lopment of a mutator phenotype.