A CASE-CONTROL STUDY OF NONRANDOM DISTRIBUTION OF BLEOMYCIN-INDUCED CHROMATID BREAKS IN LYMPHOCYTES OF LUNG-CANCER CASES

We used a case-control study design to determine the association betwe en bleomycin-induced chromatid breaks and the risk of lung cancer in g eneral and by specific histopathological types. Lymphocytes from prima ry blood cultures of 78 controls and 75 cases with 4 histopathological types of lung cancer were treated with 0.03 unit/ml bleomycin for 5 h , and the frequency of induced chromatid breakage and the locations of the breaks were determined in Q-banded preparations. After adjustment for their length, the larger chromosomes had more breaks than the sma ller chromosomes in both cases and controls. The cases had significant ly more breaks on chromosomes 4 and 5 than the controls did, with odds ratios (ORs) of 4.9 [95% confidence limits (CL), 2.0, 11.7] and 3.9 ( 95% CL, 1.6, 9.3), respectively. When the lung cancers mere classified by histopathological type, adenocarcinomas had significantly more bre aks on chromosomes 4 and 5, with ORs of 3.0 (95% CL, 1.0, 8.7) and 3.5 (95% CL, 1.2, 10.7), respectively. For squamous cell carcinoma, the O Rs were significantly elevated for breaks on chromosomes 2, 4, and 5 w ith ORs of 3.5 (95% CL, 1.0, 11.7), 10.2 (95% CL, 2.5, 41.9), and 7.9 (95% CL, 1.9, 32.8). For small cen carcinoma, breaks on chromosomes 2 and 4 showed significantly increased ORs of 33.2 (95% CL, 2.2, 513.3) and 20.4 (95% CL, 1.7, 250.1), respectively. However, no specific chro matid breaks were detected in cases with large cell carcinoma. When th e frequency of chromatid breaks at specific regions was calculated, br eaks at 4p14, 4q27, 4q31, 5q21-q22, 5q31, and 5q33 were significantly more common in lung cancer cases than in controls. Lung cancer risk ha d a dose-response relationship with breaks on chromosomes 4 and 5. Cig arette smoking had a strong interaction with breaks on chromosomes 2, 4, and 5. The findings suggest that the susceptibility of particular c hromosome loci to mutagenic damage mag be a risk factor for specific t ypes of lung cancer.