||5R01CA076016-12 Interpret this number
||The Molecular Epidemiology of Ovarian Cancer
In the current funding period of our study entitled ?The Molecular Epidemiology of Ovarian Cancer?
(RO1CA176016, PI: Dr. Schildkraut,), we have studied the relationship between candidate genes in the
DNA damage and repair pathway and ovarian cancer risk using data from the North Carolina Ovarian
Cancer Study (NCOCS). To date, we have examined the relationship between 53 genes and 652 SNPs in
this pathway. The first phase of our study we have identified strong association between genes on the
DNA repair pathway and ovarian cancer risk. In this competitive renewal we propose to expand the scope
of our Phase 1 genotyping to further investigate genes the DNA repair and apopotosis pathways and to
mount a second candidate gene association study. We hypothesize that a subset of the previouslyexamined
SNPs in genes with known roles in DNA damage and repair will emerge as risk factors for
ovarian cancer, and that newly-examined SNPs in genes within this and related pathways will be
associated with risk of ovarian cancer. The proposed study will be designed to optimally accumulate
evidence on candidates while simultaneously reducing the false positive rate among included SNPs
and minimizing the rate of false negatives. Analyses will examine risk modification across subgroups
defined by age, race, body mass index, oral contraceptive use, pregnancy history, histology and other
exposures. The ultimate goal is to improve our ability to identify women at genetic risk of ovarian cancer
and to design targeted intervention strategies to prevent this fatal disease. To this end, we propose to
genotype in 2,075 invasive serous epithelial ovarian cancer cases and 2,075 age-matched controls of
European descent to determine the relationship between genetic variants in DNA response and repair and
related pathways. We will evaluate the association between over 2,000 SNPs with risk of ovarian cancer.
We will access subjects from six independent case-control studies: North Carolina (Dr.Schildkraut), the
Mayo Clinic (Dr. Goode), New England (Drs. Terry and Cramer), Pittsburgh (Dr. Ness), Los Angeles (Drs.
Pearce and Wu) and Seattle (Dr. Rossing). Further confirmation will be pursued in collaboration with the
Ovarian Cancer Association Consortium (OCAC) in the future.