This study will investigate the relation between postmenopausal endogenous
levels of estrogens and subsequent development of endometrial cancer. In
premenopausal women, estrogens unopposed by progesterone are known to
stimulate endometrial cell division, providing a rationale for the role of
estrogens in endometrial carcinogenesis. In postmenopausal women,
estrogen replacement therapy is associated with an increased risk of
endometrial cancer. However, there is no direct epidemiologic evidence
that the physiologically low levels of endogenous estrogens observed after
menopause are positively associated with endometrial cancer risk. In the
face of increasing long-term use of estrogen replacement therapy, to
prevent cardiovascular disease and osteoporosis, a better understanding of
the role of endogenous estrogens may help develop prescription guidelines.
The proposed study will use an existing resource of frozen serum samples
collected between 1985 and 1991 in a cohort of 6071 postmenopausal women
enrolled in a study of breast cancer and endogenous hormones (New York
University Women's Health Study, NYUWHS). The specific aims of the
proposal are: 1) to identify incident cases of endometrial cancer, using
follow-up information generated by the NYUWHS until mid-1998; 2) to
conduct a case-control study of endometrial cancer nested within this
cohort. Sixty incident cases of endometrial cancer are expected to occur
by the end of follow-up. For each case, four controls, matched on age and
date of blood donation, will be selected. Controls will have to be alive,
free of disease and with an intact uterus at time of diagnosis of the
case. Information on known risk factors will be collected through telephone
interviews. Serum samples will be assayed for estrone, estradiol,
percent estradiol bound to sex hormone binding globulin and percent free
estradiol. Conditional logistic regression for matched data will be used
to assess whether higher levels of endogenous estrogens are associated
with a higher risk of endometrial cancer. The study will also investigate
whether the role of obesity in endometrial cancer can be explained by its
action on endogenous estrogens.
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