DESCRIPTION: Experimental and clinical evidence suggests that endogenous sex
hormones and insulin-like growth factor 1 (IGF-I) may contribute to the
etiology of breast cancer. We propose to examine whether most known
polymorphisms of a number of genes involved in the biosynthesis and catabolism
of estrogens (CYP11a, CYP17, EDH17beta2, CYP1A1, CYP1A2, CYP1B1, COMT), and
those for the androgen receptor, estrogen receptor and IGF-I genes are related
to the risk of breast cancer and proliferative breast disease. Also, we plan to
study whether these polymorphisms and plasma levels of IGF-I and insulin-like
growth factor binding protein-3 (IGFBP-3) are related to degree of cell
proliferation in non-cancerous tissues from women with fibrocystic disease.
We propose to conduct a case-control study nested within an ongoing randomized
Breast Self Examination Trial being conducted in Shanghai, China, involving
285,628 women. We will analyze blood specimens that will have been collected
and received in Seattle by the end of year 2000 for a study of diet, cell
proliferation, and breast cancer in Shanghai (R01 CA75332) from approximately
542 women with breast cancer, 627 women with fibrocystic disease, and 793
age-matched controls. Demographic variables, reproductive history, and (for
cases) extent of cell proliferation of non-cancerous breast tissue based on
morphological classification will be available from the dietary study.
We will test the hypotheses that 1) the risk of breast cancer and proliferative
breast disease are related to one or more alleles that are believed to
correspond to a high level of estradiol, testosterone or IGF-I (adjusted for
IGFBP-3), or high activities of androgen receptors and estrogen receptors; 2)
the mechanism by which some of the risk alleles exert their influence is
through the promotion of cell proliferation; and 3) the effect of some of the
risk alleles may be modified by reproductive and other factors associated with
Because of the size and scope of the study, we believe it has the potential to
substantially advance our understanding of the etiology of breast cancer. Our
ultimate goal is to provide information to identify women at high risk of
breast cancer, and to aid in the formulation of prevention strategies for these
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