DESCRIPTION (provided by applicant):
Ovarian cancer is the second most common malignancy of the female genital
tract and the most common cause of death from gynecological cancer in the
United States. At present, only 20 percent of ovarian cancer patients are
diagnosed at localized stage and the majority of patients are diagnosed at
advanced stages characterized by poor prognosis. One of the most promising
approaches to improved screening and identification of women at risk of
ovarian cancer could be the use of serum biological markers. The first
biomarker that was proposed for this purpose was an antigenic determinant
CA125. However, CA125 as a single measurement detects only about half of the
ovarian cancers at Stage I and it may be elevated in benign gynecological
conditions. Consequently, CA125 used on a single occasion, as a solitary
marker, does not have an adequate sensitivity and specificity as a screening
We hypothesize that the new strategies involving use of multiple biomarkers
can substantially improve the sensitivity and specificity of screening methods
for ovarian cancer. With this application, we propose to concentrate on a
combination of CA125 with novel promising biomarkers affecting different
pathways of ovarian carcinogenesis, which include: lysophosphatidic acid
(LPA), a phospholipid growth factor involved in mitogenesis and proliferation
of ovarian epithelial cells; and soluble Fas (sFas), a marker of impaired
apoptosis, which may lead to formation and persistence of ovarian stroma
inclusion cysts and subsequent carcinogenesis.
We propose to assess a potential value of the panel of serum biomarkers
(CA125, LPA, sFAS) for early detection of ovarian cancer in a case-control
study nested within three participating prospective cohorts: the New York
University Women's Health Study; the Northern Sweden Health and Disease Study;
and the Janus Serum Bank at Oslo University Hospital, Norway.
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