MUTAGEN SENSITIVITY IN UPPER AERODIGESTIVE TRACT CANCER - A CASE-CONTROL ANALYSIS

Variability in DNA repair capability may be a determinant of interindi vidual difference in susceptibility to carcinogenic exposures. A cytog enetic assay which quantifies chromosomal breakage induced by in vitro exposure to a clastogen provides an indirect measure of repair. We re port the results of a case-control study of upper aerodigestive tract cancers assessing differences in mutagen sensitivity based on this ass ay. There were 108 cases with previously untreated squamous cell cance rs and 108 age and sex frequency-matched controls selected from blood donors to The University of Texas M. D. Anderson Cancer Center. Sixty- nine% of the cases, compared with 44% of the controls, were classified as mutagen sensitive (breaks per cell greater-than-or-equal-to 0.8). On multivariate analysis, mutagen sensitivity [odds ratio (OR), 2.5], heavy cigarette smoking (OR, 4.8), and heavy alcohol consumption (OR, 3.1) were associated with significantly increased risk. Stratified ana lyses showed that the combined effects of cigarette smoking (OR, 8.1) and mutagen sensitivity (OR, 3.2) were suggestive of a multiplicative effect (OR, 23.0). The combined estimate for alcohol use (OR, 3.0) and mutagen sensitivity (OR, 3.0) was 5.8. These data confirm those of a previously published preliminary study of upper aerodigestive cancers and underscore the importance of considering interindividual susceptib ility in cancer risk characterization, even for those cancers with wel l quantified exposures.