) Estrogens play an important role in the etiology of breast cancer. Cytochrome P450-1A2 (CYP1A2) and 3A4(CYP3A4) are two of the major enzymes in estrogen hydroxylation, forming biologically distinct metabolites: 2-hydroxy estrogens and 16alpha-/4-hydroxy estrogens, respectively. It is thus conceivable that the risk of breast cancer may differ among women with different activities of these enzymes. Preliminary results from our pilot study suggest that high CYP3A4 activity or low CYP1A2 activity may be related to a substantially elevated risk of breast cancer. To extend these novel findings to a full-scale study, we propose to analyze urine samples collected from a subset (250 case-control pairs) of study participants recruited in the Shanghai Breast Cancer Study, an ongoing NCI-funded population-based case-controlled study among Chinese women in Shanghai (R01 CA64271). In addition to in-person interviews and collection of fasting morning blood and urine samples, in vivo urinary caffeine tests will also have been completed for these women by September, 1998. The urine samples collected after caffeine intake will be assayed for caffeine metabolites to determine the activity of CYP1A2, and overnight urine samples will be assayed for cortisol metabolites to determine the activity of CYP3A4. Because the caffeine tests and overnight urine collections are conducted prior to any cancer therapy for the breast cancer cases, the potential influence of disease and its sequaele should be minimized. The enzyme activity data collected from this study will be analyzed jointly with data collected from the main study to evaluate the association of CYP1A2 and CYP3A4 activities with breast cancer risk.
| Zheng, W; Jin, F; Dunning, L A et al. (2001) Epidemiological study of urinary 6beta-hydroxycortisol to cortisol ratios and breast cancer risk. Cancer Epidemiol Biomarkers Prev 10:237-42 |
