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Genetic and Environmental Determinants on Tissue Response to in Vitro Carcinogen Exposure and Risk of Breast Cancer¹

Departments of Gastrointestinal Medical Oncology [D. L., P. C., W. Z., J. Z.], Epidemiology [F. L. W., E. P., M. L. B.], Surgical Oncology [S. E. S.], and Pathology [A. A. S.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

To test the hypothesis that individual susceptibility to carcinogen exposure is a risk factor for breast cancer, we measured DNA adduct formation in normal breast tissues treated in vitro with 4 µM benzo(a)pyrene in 76 cancer cases and 60 noncancer controls. We found a significantly higher level of adducts (134.6 ± 21.2/10⁹) among cases compared with controls (66.9 ± 7.5; P = 0.007). The level of adducts was significantly associated with the risk of breast cancer (odds ratio, 4.38; 95% confidence interval, 1.04 to 18.50; P = 0.044) after adjusting for confounders. Stratified analysis and regression analysis demonstrated that race, pack-years of smoking, family history of breast cancer, and CYP1B1 genotype were significant predictors of the level of benzo(a)pyrene-induced adducts in the breast tissues. These observations suggest that genetic susceptibility to carcinogen exposure may play an important role in breast carcinogenesis.

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