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

Abstract

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.

• Authors: Donghui Li, Farzana L Walcott, Ping Chang, Weiqing Zhang, Jijiang Zhu, Elaine Petrulis, Sonja E Singletary, Aysegul A Sahin, Melissa L Bondy
• Journal: Cancer research (Cancer Res) Vol. 62 Issue 16 Pg. 4566-70 (Aug 15 2002) ISSN: 0008-5472 [Print] United States
• PMID: 12183407 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• DNA Adducts
• Environmental Pollutants
• benzo(a)pyrene-DNA adduct
• Benzo(a)pyrene
• DNA
• Cytochrome P-450 Enzyme System
• Aryl Hydrocarbon Hydroxylases
• CYP1B1 protein, human
• Cytochrome P-450 CYP1A1
• Cytochrome P-450 CYP1B1
• Glutathione Transferase
• glutathione S-transferase M1

Topics

• Adult
• Aryl Hydrocarbon Hydroxylases
• Benzo(a)pyrene (metabolism, toxicity)
• Breast Neoplasms (chemically induced, genetics, metabolism)
• Case-Control Studies
• Cocarcinogenesis
• Cytochrome P-450 CYP1A1 (genetics, metabolism)
• Cytochrome P-450 CYP1B1
• Cytochrome P-450 Enzyme System (genetics, metabolism)
• DNA (drug effects, metabolism)
• DNA Adducts (metabolism)
• Environmental Exposure
• Environmental Pollutants (adverse effects)
• Female
• Genetic Predisposition to Disease
• Glutathione Transferase (genetics, metabolism)
• Humans
• Middle Aged
• Risk Factors
• Smoking (adverse effects)