A case-control study of nonrandom distribution of bleomycin-induced chromatid breaks in lymphocytes of lung cancer cases

Cancer Res. 1995 Feb 1;55(3):557-61.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Black People
  • Black or African American
  • Bleomycin / pharmacology*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology
  • Case-Control Studies
  • Chromosome Aberrations*
  • Chromosome Mapping
  • Chromosomes, Human, Pair 18
  • Chromosomes, Human, Pair 2
  • Chromosomes, Human, Pair 4
  • Chromosomes, Human, Pair 5
  • Female
  • Humans
  • Lung Neoplasms / classification
  • Lung Neoplasms / epidemiology*
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Lymphocytes / drug effects*
  • Male
  • Mexican Americans
  • Mexico
  • Middle Aged
  • Minority Groups
  • Reference Values
  • Sex Characteristics
  • United States

Substances

  • Bleomycin