MUTAGEN SENSITIVITY AS A BIOLOGICAL MARKER OF LUNG-CANCER RISK IN AFRICAN-AMERICANS

Cigarette smoking is the major determinant of lung cancer. However, on ly a fraction of smokers develops lung cancer; genetically determined susceptibility factors seem to play an important role also. Previous c ase-control studies have shown that in vitro bleomycin-induced mutagen sensitivity is an independent risk factor for head-and-neck cancers, and preliminary data suggest a similar association with lung cancer. H owever, these studies were almost exclusively performed on Caucasian p opulations. To test whether ethnic differences in cancer risk are due to differences in mutagen sensitivity, we are using the in vitro mutag en sensitivity assay to conduct a case-control study of mutagen sensit ivity and lung cancer risk in low-risk (Mexican-American) and high-ris k (African-American) groups. Here we report the results of our ongoing study of 209 African-Americans (90 cases and 119 controls) in the Hou ston-Galveston area. Mexican-American data will be reported separately as case accrual increases. Predictably, all measures of cigarette smo king status (including intensity, duration, tar content, depth of inha lation, and type of cigarette) were significant predictors of risk. In addition, 55.3% of the cases were mutagen sensitive (defined as great er than or equal to 1 break/cell), compared with 24.6% of the controls , with an age-, sex-, and smoking-adjusted odds ratio (OR) of 3.7 (95% confidence limits = 1.4, 9.4). Of interest, higher risks were noted f or former smokers (OR = 5.4) compared with current smokers (OR = 3.1) and especially for younger former smokers (<55 years). By histologic-s pecific analysis, mutagen sensitivity was significantly associated wit h risk for adenocarcinoma (OR = 4.8) and squamous cell carcinoma (OR = 8.5). Stratified analysis showed that there was an interaction betwee n mutagen sensitivity and current and former smoking and heavy smoking (greater than or equal to 20 pack-years) that appeared to be greater than multiplicative. These risk estimates are generally higher than th ose we reported for head-and-neck cancer in Caucasian populations. Fur ther research should focus on the cytogenetic and molecular evaluation of whether the break sites are random or occur at specific sites and on comparisons with DNA repair assay systems.