Bleomycin-induced chromosome breaks as a risk marker for lung cancer: a case-control study with population and hospital controls.
Environmental exposure to carcinogens and individual susceptibility play significant roles in cancer risk. Suboptimal DNA repair capability, measured by quantifying mutagen-induced chromosome breaks, might explain variable host susceptibility to environmental carcinogens. In an ongoing lung cancer case-control study, we compared individual sensitivity to bleomycin-induced chromosome breaks in 152 non-small cell lung cancer patients with 94 population controls and 85 hospital controls with no history of cancer. Mutagen sensitivity was measured by mean number of chromatid breaks per cell in cultured peripheral blood lymphocytes treated with bleomycin. Non-parametric tests and chi(2) tests were used to determine the statistical significance of the crude case-control comparisons, followed by logistic regression to adjust for important covariates. The mean number of bleomycin-induced breaks per cell was 1.01 for the cases compared with 0.86 for hospital controls (P < 0.01) and 0.89 for population controls (P < 0.01). The mean number of breaks per cell was 1.01 for those >65 years old and 0.81 for those < or = 65 years old (P < 0.01) among population controls. Defining bleomycin sensitive as >0.84 break/cell (the median level in population controls), 67% of the cases were bleomycin sensitive compared with 49% of the hospital controls [adjusted odds ratio (OR) = 2.69, 95% confidence interval (CI) = 1.44, 5.04], and 51% of the population controls (adjusted OR = 2.18, 95% CI = 1.13, 4.21). Our data indicate that the increased number of bleomycin-induced chromosome breaks was significantly associated with an increased risk of lung cancer in the first 331 subjects.
Zheng
Yun-Ling
YL
Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Loffredo
Christopher A
CA
Yu
Zhipeng
Z
Jones
Raymond T
RT
Krasna
Mark J
MJ
Alberg
Anthony J
AJ
Yung
Rex
R
Perlmutter
Donna
D
Enewold
Lindsey
L
Harris
Curtis C
CC
Shields
Peter G
PG
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D001761:Bleomycin / Q000009:adverse effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000235:genetics*; D016022:Case-Control Studies; D002869:Chromosome Aberrations; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008396:Maryland / Q000453:epidemiology; D008875:Middle Aged; D009153:Mutagens / Q000009:adverse effects; D011159:Population Surveillance; D012307:Risk Factors
D000964:Antimetabolites, Antineoplastic; D009153:Mutagens; D001761:Bleomycin