Abstract
Polymorphisms in the cytochrome P450 1B1 (
CYP1B1
) and glutathione S-transferase (
GST
) drug metabolic enzymes, which are responsible for metabolic activation/detoxification of estrogen and environmental carcinogens, were analyzed for their association with breast cancer risk in 541 cases and 635 controls from a North Carolina population. Each polymorphism, altering the catalytic function of their respective enzymes, was analyzed in Caucasian and African-American women. As reported in previous studies, individual polymorphisms did not significantly impact breast cancer risk in either Caucasian or African-American women. However, African-American women exhibited a trend towards a protective effect when they had at least one
CYP1B1
119S allele (OR=0.53; 95% CI=0.20–1.40) and increased risk for those women harboring at least one
CYP1B1
432V allele (OR=5.52; 95% CI=0.50–61.37). Stratified analyses demonstrated significant interactions in younger (age ≤60) Caucasian women with the
CYP1B1
119SS genotype (OR=3.09; 95% CI=1.22–7.84) and younger African-American women with the
GSTT1
null genotype (OR=4.07; 95% CI=1.12–14.80). A notable trend was also found in Caucasian women with a history of smoking and at least one valine allele at
GSTP1
114 (OR=2.12; 95% CI=1.02–4.41). In Caucasian women, the combined
GSTP1
105IV/VV and
CYP1B1
119AA genotypes resulted in a near 2-fold increase in risk (OR=1.96; 95% CI=1.04–3.72) and the three way combination of
GSTP1
105IV/VV,
CYP1B1
119AS/SS and
GSTT1
null genotypes resulted in an almost 4-fold increase in risk (OR=3.97; 95% CI=1.27–12.40). These results suggest the importance of estrogen/carcinogen metabolic enzymes in the etiology of breast cancer, especially in women before the age of 60, as well as preventative measures such as smoking cessation.
