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.
Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. dli@mdanderson.org
Donghui
D
Li
Farzana L
FL
Walcott
Ping
P
Chang
Weiqing
W
Zhang
Jijiang
J
Zhu
Elaine
E
Petrulis
Sonja E
SE
Singletary
Aysegul A
AA
Sahin
Melissa L
ML
Bondy
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