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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/4793

Title: Cytochrome P450 1A2 (CYP1A2) activity and risk factors for breast cancer: a cross-sectional study
Authors: Hong, Chi-Chen,
Tang, Bing-Kou,
Hammond, Geoffrey L,
Tritchler, David,
Yaffe, Martin,
Boyd, Norman F, boyd_at_uhnres.utoronto.ca
Keywords: anthropometric measurements
insulin-like growth factor-1
mammographic density
sex hormones
Issue Date: 7-May-2004
Publisher: BioMed Central Ltd.
Citation: Breast Cancer Res 2004(7 May); 6(4): R352-R365
Abstract: INTRODUCTION: 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. CONCLUSION: 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.
Description: Conclusion: Results from the present cross-sectional study suggests that several factors associated with breast cancer risk are associated with CYP1A2 activity, including SHBG and free estradiol levels, insulin and IGF-1, blood lipids and cholesterol, body size, and smoking status. Some of the observed associations, however, were contrary to hypothesized directions and suggest that increased CYP1A2 function may be associated with increased risk for breast cancer. These preliminary findings need confirmation in future studies. The association of risk factors with the activity of metabolic enzymes, particularly those under substantial genetic control, may suggest important pathways in the development of breast cancer. Further research is required to elucidate the relationships between CYP1A2 genotype, CYP1A2 phenotype, their influence on risk factors associated with breast cancer, and their impact on breast cancer risk.
URI: http://hdl.handle.net/1807/4793
Appears in Collections:Epidemiology and Prevention

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