Abstract
IntroductionBreast cancer risk may be determined by various genetic, metabolic, and lifestyle factors that alter sex hormone metabolism. Cytochrome P450 1A2 (CYP1A2) is responsible for the metabolism of estrogens and many exogenous compounds, including caffeine.MethodsIn a cross-sectional study of 146 premenopausal and 149 postmenopausal women, we examined the relationships between CYP1A2 activity and known or suspected risk factors for breast cancer. Blood levels of sex hormones, lipids, and growth factors were measured. In vivo CYP1A2 activity was assessed by measuring caffeine metabolites in urine. Stepwise and maximum R regression analyses were used to identify covariates related to CYP1A2 activity after adjustment for ethnicity.ResultsIn both menopausal groups CYP1A2 activity was positively related to smoking and levels of sex hormone binding globulin. In premenopausal women, CYP1A2 activity was also positively related to insulin levels, caffeine intake, age, and plasma triglyceride levels, and negatively related with total cholesterol levels and body mass index. In postmenopausal women CYP1A2 activity was positively associated with insulin-like growth factor-1, and negatively associated with plasma triglyceride, high-density lipoprotein cholesterol, and age at menarche.ConclusionThese results suggest that CYP1A2 activity is correlated with hormones, blood lipids, and lifestyle factors associated with breast cancer risk, although some of the observed associations were contrary to hypothesized directions and suggest that increased CYP1A2 function may be associated with increased risk for breast cancer.
Highlights
Breast cancer risk may be determined by various genetic, metabolic, and lifestyle factors that alter sex hormone metabolism
In postmenopausal women Cytochrome P450 1A2 (CYP1A2) activity was positively associated with insulinlike growth factor-1, and negatively associated with plasma triglyceride, high-density lipoprotein cholesterol, and age at menarche
These results suggest that CYP1A2 activity is correlated with hormones, blood lipids, and lifestyle factors associated with breast cancer risk, some of the observed associations were contrary to hypothesized directions and suggest that increased CYP1A2 function may be associated with increased risk for breast cancer
Summary
Breast cancer risk may be determined by various genetic, metabolic, and lifestyle factors that alter sex hormone metabolism. Cytochrome P450 1A2 (CYP1A2) is responsible for the metabolism of estrogens and many exogenous compounds, including caffeine. Epidemiologic evidence suggests that endocrine factors alter breast cancer risk. In both premenopausal and postmenopausal women cancer risk is associated with events that alter hormonal balance, such as age at menarche, parity, body weight, body fat distribution, and use of exogenous hormones. Function of the cytochrome P450 1A2 (CYP1A2) enzyme might play a role in determining estrogen exposure because it is principally responsible for the metabolism of 17β-estradiol after initial conversion to estrone. The enzyme is most active in catalyzing 2hydroxylations [3], and in humans between 40% and 50%
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