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 between bleomycin-induced chromatid breaks and the risk of lung cancer in general and by specific histopathological types. Lymphocytes from primary 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 smaller chromosomes in both cases and controls. The cases had significantly 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 were classified by histopathological type, adenocarcinomas had significantly more breaks 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 ORs were significantly elevated for breaks on chromosomes 2, 4, and 5 with 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 cell 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 chromatid breaks were detected in cases with large cell carcinoma. When the frequency of chromatid breaks at specific regions was calculated, breaks at 4p14, 4q27, 4q31, 5q21-q22, 5q31, and 5q33 were significantly more common in lung cancer cases than in controls. Lung cancer risk had a dose-response relationship with breaks on chromosomes 4 and 5. Cigarette smoking had a strong interaction with breaks on chromosomes 2, 4, and 5. The findings suggest that the susceptibility of particular chromosome loci to mutagenic damage may be a risk factor for specific types of lung cancer.
Wu
X
X
Department of Cell Biology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Hsu
T C
TC
Annegers
J F
JF
Amos
C I
CI
Fueger
J J
JJ
Spitz
M R
MR
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D044383:Black People; D001761:Bleomycin / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology; D016022:Case-Control Studies; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D002887:Chromosomes, Human, Pair 18; D002889:Chromosomes, Human, Pair 2; D002894:Chromosomes, Human, Pair 4; D002895:Chromosomes, Human, Pair 5; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000145:classification / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D017058:Mexican Americans; D008800:Mexico; D008875:Middle Aged; D008913:Minority Groups; D012016:Reference Values; D012727:Sex Characteristics; D014481:United States; D001741:Black or African American
D001761:Bleomycin