Background: Although several risk factors have been
established for ovarian cancer, a better understanding of potentially modifiable
risk factors is necessary in order to identify strategies for prevention.
Aside from increasing age and a positive family history, the strongest
known risk factors for epithelial ovarian cancer are nulliparity, no use
of oral contraceptives, and having intact fallopian tubes. These factors
are not readily modifiable. Ovarian cancer is very heterogeneous at both
a histologic and genetic level, and there is increasing evidence that the
different histologic subtypes of ovarian cancer may be etiologically different.
Studies that treat ovarian cancers as a single entity, without accounting
for this variability, may compromise their ability to identify factors
associated with development of the disease. Similarly, common low-risk
genetic variants may modify disease susceptibility and may alter the effects
of ovarian cancer risk factors.
Objective: The aim of this program is to use histologic
and novel molecular subtypes of ovarian tumors to study the association
between epidemiologic risk factors, low-risk genes, and subtypes of ovarian
cancer, thereby addressing the heterogeneity of the disease and of susceptibility
to environmental exposures. To this end, we will establish a multi-centre
population-based resource involving the collection of epidemiologic data
and biospecimens, including fresh tumor tissue, from cases and matched
controls.
Hypothesis: We hypothesize that different subtypes of
ovarian cancer, at the histologic and genetic level, are etiologically
distinct and will be associated with different epidemiologic risk factors,
with an emphasis on potentially modifiable factors. Similarly, we propose
that low-risk genes in key pathways may influence susceptibility to ovarian
cancer and may modify the effects of known risk factors
Specific Aims:
• To create a multi-centre resource covering over 1,000
population-based incident cases of primary epithelial ovarian cancer
and a similar number of matched controls combining epidemiologic data
and biospecimens (blood, urine, paraffin-embedded tumor blocks, and
fresh tumor tissue)
• To determine molecular subtypes of ovarian cancer by
DNA microarray-based expression analysis of ovarian tumor samples and
to link these subtypes to clinical and epidemiologic characteristics
• To study associations between epidemiologic risk factors
and ovarian cancer by histologic and tumor subtypes with an emphasis
on potentially modifiable risk factors
• To evaluate the association of variants in candidate
low-risk genes (in double-stranded DNA repair pathways and androgen/progesterone
pathways) and ovarian cancer, and to stratify these associations by
tumor subtypes.
Study Design: This Program Project is based upon an
Australian-wide collaborative population-based case-control study, the
Australian Ovarian Cancer Study. Cases will be identified through an existing
network of gynecologic oncologists covering more than 85% of the Australian
population and interviewed by trained nurses as soon as possible after
diagnosis. With their informed consent, participants will be interviewed,
and blood, urine, and tumor (blocks and fresh tissue) will be collected.
Controls will be identified through a population-based register and interviewed
and asked to provide blood and urine samples, as for cases.
