The benefits and risks of estrogen replacement therapy continue to
confuse women and their physicians. Recent evidence suggests that
estrogen replacement may be associated with reductions in large bowel
cancer, a common disease among postmenopausal women. Further study
of this potentially important association would provide more precise
estimates of the magnitude of effect, identify salient patterns of
use, and, importantly, supply insights into the biology of this tumor
in women.
A population-base case-control study is proposed to evaluate the
association between postmenopausal hormones and the occurrence of
colorectal cancer. This study will specifically assess use of
estrogens with and without progestin, the duration and currency of
hormone use, and inter-relationships with body mass. Additional aims
of this study are to elucidate the mechanisms of this inverse
association, specifically the relationship of HRT to hormone
receptors and proliferation in the bowel, and to examine the
modifying role of more common cancer susceptibility genes influencing
the metabolism of estrogens. Over a three year period, interviews
will be conducted with 1,100 women with newly diagnosed cancer of the
colon or rectum selected from the population. In addition to the
structured telephone interview, fixed diagnostic tissue will be
obtained from 540 case in order to evaluate estrogen-receptor status
and proliferation markers. Blood samples on a sample of 600 (most
with diagnostic tissue) cases and 600 controls will be obtained for
genetic studies of polymorphisms relevant to estrogen metabolism and
function, specifically CYP17 and the estrogen receptor gene. The
proposed study and its extensions should provide clear evidence for
the degree to which HRT is protective against colorectal cancer and
permit the determination of some of the relevant pathways for that
protection.
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- The DCCPS Team.