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 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.
Li
Donghui
D
Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. dli@mdanderson.org
Walcott
Farzana L
FL
Chang
Ping
P
Zhang
Weiqing
W
Zhu
Jijiang
J
Petrulis
Elaine
E
Singletary
Sonja E
SE
Sahin
Aysegul A
AA
Bondy
Melissa L
ML
D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases; D001564:Benzo(a)pyrene / Q000378:metabolism / Q000633:toxicity*; D001943:Breast Neoplasms / Q000139:chemically induced* / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D003043:Cocarcinogenesis; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D018736:DNA Adducts / Q000378:metabolism; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000009:adverse effects; D005260:Female; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects
D001189:Aryl Hydrocarbon Hydroxylases; D001564:Benzo(a)pyrene; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System; D004247:DNA; D018736:DNA Adducts; D004785:Environmental Pollutants; D005982:Glutathione Transferase; C056612:benzo(a)pyrene-DNA adduct; C585496:CYP1B1 protein, human