© 1998 by Oxford University Press
Journal of the National Cancer Institute, Vol. 90, No. 18, 1393-1399,
September 16, 1998
©Copyright 1998 Oxford University Press
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Benzo[a]pyrene Diol Epoxide and Bleomycin Sensitivity and Susceptibility to Cancer of Upper Aerodigestive Tract
Affiliations of authors: X. Wu, Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, and The University of Texas School of Public Health, Houston; J. Gu, C. I. Amos, H. Jiang, M. R. Spitz (Department of Epidemiology), W. K. Hong (Department of Thoracic and Head and Neck Medical Oncology), J. J. Lee (Department of Biomathematics), R. J. Winn (Department of Community Oncology), The University of Texas M. D. Anderson Cancer Center; K. K.-W. Fu, Radiation Oncology Department, University of California, San Francisco; J. Cooper, Department of Radiation Oncology, New York University Medical Center, NY.
Correspondence to: Xifeng Wu, M.D., Ph.D., Box 189, Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030 (xwu{at}notes.mdacc.tmc.edu).
Abstract
Background: Tobacco smoking is an established risk factor
for cancers of the upper aerodigestive tract, and measurement of
chromosomal aberrations, i.e., chromatid breaks, induced in lymphocytes
in vitro by bleomycin has been shown to be a predictor of risk
for these cancers. In a case–control study, we recruited case subjects
who were previously treated with surgery and/or radiotherapy for stage
I or stage II squamous cell carcinoma of the head and neck to test the
hypothesis that lymphocytic chromatid breaks induced by
benzo[a]pyrene diol epoxide (BPDE), a tobacco mutagen, may
also be associated with risk of developing cancers of the upper
aerodigestive tract. Methods: Case subjects were matched to
control subjects on the basis of age, sex, ethnicity, and smoking
status. Primary lymphocytes from 67 case subjects and 81 control
subjects were treated with 2 µM BPDE for 24 hours, and the
frequency of induced chromatid breaks was determined. All statistical
tests were two-sided. Results: Lymphocytes from case subjects
compared with lymphocytes from control subjects showed significantly
more breaks per cell induced by BPDE (mean ± standard deviation,
0.77 ± 0.38 versus 0.49 ± 0.25; P<.001). Lymphocytes
from 64.2% of case subjects were sensitive to BPDE (using a cutoff
value of 
0.60 break per cell). Subjects in the highest quartile of
chromatid breaks had an approximately 20-fold increased risk of cancer
compared with those in the lowest quartile after adjustment for age,
sex, ethnicity, and smoking status. The association between BPDE
sensitivity and cancer risk was higher in former smokers than in
current smokers and higher in younger patients than in older patients.
Subjects with sensitivity to both BPDE and bleomycin were at a
19.2-fold increased risk of cancer compared with those who were not
sensitive to either agent. Conclusions: Mutagen sensitivity
assays may aid in identifying individuals at risk of cancer, and use of
parallel assays with two mutagens may improve risk predictability. [J
Natl Cancer Inst 1998;90:1393–9]
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