DESCRIPTION: (Applicant's Description) 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.
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