Cytochrome P450 1A2 (CYP1A2) activity and risk factors for breast cancer: a cross-sectional study.
BACKGROUND
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.


METHODS
In 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.


RESULTS
In 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.


CONCLUSIONS
These 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.
Hong
Chi-Chen
CC
Division of Epidemiology and Statistics, Ontario Cancer Institute, Toronto, Ontario, Canada. chong@uhnres.utoronto.ca
Tang
Bing-Kou
BK
Hammond
Geoffrey L
GL
Tritchler
David
D
Yaffe
Martin
M
Boyd
Norman F
NF
D000328:Adult; D000367:Age Factors; D001835:Body Weight / Q000502:physiology; D001943:Breast Neoplasms / Q000097:blood / Q000201:enzymology* / Q000208:ethnology / Q000235:genetics; D003430:Cross-Sectional Studies; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism*; D005006:Ethnicity; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008019:Life Style / Q000208:ethnology; D008055:Lipids / Q000097:blood; D008875:Middle Aged; D010298:Parity / Q000502:physiology; D017698:Postmenopause / Q000097:blood; D011237:Predictive Value of Tests; D017697:Premenopause / Q000097:blood; D012307:Risk Factors
D012739:Gonadal Steroid Hormones; D007328:Insulin; D008055:Lipids; D007334:Insulin-Like Growth Factor I; D019388:Cytochrome P-450 CYP1A2