Genetic and environmental determinants on tissue response to in vitro carcinogen exposure and risk of breast cancer

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 micro M benzo(a)pyrene in 76 cancer cases and 60 noncancer controls. We found a significantly higher leve...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2002-08, Vol.62 (16), p.4566-4570
Main Authors: DONGHUI LI, WALCOTT, Farzana L, PING CHANG, WEIQING ZHANG, JIJIANG ZHU, PETRULIS, Elaine, SINGLETARY, Sonja E, SAHIN, Avseeul A, BONDY, Melissa L
Format: Article
Language:English
Subjects:
Adult
Aryl Hydrocarbon Hydroxylases
Benzo(a)pyrene - metabolism
Benzo(a)pyrene - toxicity
Biological and medical sciences
Breast Neoplasms - chemically induced
Breast Neoplasms - genetics
Breast Neoplasms - metabolism
Case-Control Studies
Cocarcinogenesis
Cytochrome P-450 CYP1A1 - genetics
Cytochrome P-450 CYP1A1 - metabolism
Cytochrome P-450 CYP1B1
Cytochrome P-450 Enzyme System - genetics
Cytochrome P-450 Enzyme System - metabolism
DNA - drug effects
DNA - metabolism
DNA Adducts - metabolism
Environmental Exposure
Environmental Pollutants - adverse effects
Female
Genetic Predisposition to Disease
Glutathione Transferase - genetics
Glutathione Transferase - metabolism
Gynecology. Andrology. Obstetrics
Humans
Mammary gland diseases
Medical sciences
Middle Aged
Risk Factors
Smoking - adverse effects
Tumors
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Summary: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 micro M benzo(a)pyrene in 76 cancer cases and 60 noncancer controls. We found a significantly higher level of adducts (134.6 +/- 21.2/10(9)) 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.
ISSN:0008-5472
1538-7445