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

• 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
• ISSN: 0008-5472; 1538-7445

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.