Past Research

Over the past thirty five years there have been several Registry findings, some of which include:

The BRCA 1 gene linked to germ line ovarian cancer, BRCA 1 / 2 mutations as indicators for high grade tumors, oral contraceptive use & links to mutation carriers, and the link of other cancer markers to ovarian cancer. The primary research focus of the Registry is to understand the genetic basis of ovarian cancer. We know that genetic mutations in the BRCA 1 / 2 gene accounts for only 30-40% of individuals at high risk of developing ovarian cancer. This suggests that there are additional genes responsible for ovarian cancer. If we can identify the genes that predispose to ovarian cancer, we can then develop and offer a new test to women, so that they can make informed, educated decisions about their best course of action & treatment. In addition, these new genes could become targets for therapeutic intervention.


Gynecologic Oncology, 2002

Because cancer is a complicated and frequently evolving set of diseases, research can take years and even decades before having a direct impact on patient care. That makes the significant findings discovered thanks to the Gilda Radner Familial Ovarian Cancer Registry in just over twenty years – from 1981 until the publishing of this paper in 2002 – even more remarkable.

Today, it’s commonly understood that ovarian cancer, like many other kinds of cancer, can be linked to inherited mutations within a family. But before these findings, which were only widely accepted in the mid-1990s, it was unknown why some families would have multiple cases of the disease. In the 1970s, scientists thought that environmental factors may play a role in these cases.

Therefore, the Gilda Radner Familial Ovarian Cancer Registry was established in an attempt to document the number of cases of ovarian cancer occurring in the United States, with the goal of linking them to potential environmental factors. Instead, the collection of this data made it possible for scientists to study the links between a family’s genetic make-up and their likelihood of being diagnosed.

Other important discoveries made possible by the registry include: distinguishing between the causes of site-specific ovarian cancer and cases where cancer presents in both the ovaries and breast; the importance of a patient’s age at the time of diagnosis and the impact that has on the effectiveness of screening and preventative measures; anomalies in the kinds of ovarian tumors that are found in patients with or without the BRCA1 mutation; and when a preventative removal of the ovaries is a patient’s best chance at avoiding ovarian and breast cancers.

Registry Findings


Can BRCA1 Mutations Lead to Other Kinds of Tumors?

Histopathology, FIGO Stage, and BRCA Mutation Status of Ovarian Cancers from the Gilda Radner Familial Ovarian Cancer Registry
International Society of Gynecological Pathologists, 2003

Bruce A. Werness, Susan J. Ramus, Richard A. DiCioccio, Alice S. Whittemore, Kim Garlinghouse-Jones, Ingrid Oakley-Girvan, Yoshiaki Tsukada, Patricia Harrington, Simon A. Gayther, Bruce A.J. Ponder, and M. Steven Piver

Although scientists found a link between the presence of the BRCA mutation and a patient’s chance of being diagnosed with ovarian cancer in the mid-1990s, it took many years before the cause of this link was widely understood. In a 2003 study, researchers using data from the Gilda Radner Familial Ovarian Cancer Registry began a deeper exploration of why the presence of these mutations may be an indicator of an increased risk of harder-to-fight ovarian tumors.
Using data collected by the registry, scientists were able to compare ovarian cancer patients who had mutations in the BRCA1 or BRCA2 marker with those who did not. While patients with the mutation still accounted for a small number of all ovarian cancer patients—just 10 percent—those that were part of that group appeared to have tumors that were considered higher grade.
The tumor grade system helps scientists classify how normal or abnormal tumor cells appear, and how likely they are to spread to other parts of the body. Patients with the BRCA1 or BRCA2 mutations were more likely to have a higher-grade tumor—meaning their cancer would be tougher to treat. By understanding this link, patients who have the mutation can be more aware of their risk of the disease, and doctors can best determine an effective course of treatment once a tumor has been found.


Oral Contraceptive Use and Ovarian Cancer Risk Among Carriers of BRCA1 and BRCA2 Mutations
British Journal of Cancer, 2004

AS Whittemore, RR Balise, PDP Pharoah, RA DiCioccio, Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, I Oakley-Girvan, SJ Ramus, M Daly, MB Usinowicz, K Garlinghouse-Jones, BAJ Ponder, S Buys, I Andrulis, E John, JL Hopper, and MS Piver

Use of oral contraceptives has been linked to a decreased risk of many types of ovarian cancer. But do patients who carry the BRCA1 and BRCA2 mutations fall into the same category? A 2004 study that included researchers and data from the Gilda Radner Familial Ovarian Cancer Registry explored whether use of oral birth control over several years could reduce the risk of ovarian cancer in patients who carry these mutations.
By studying the history of lifetime oral contraceptive use by patients with these genetic mutations, scientists were able to determine that their risk of ovarian cancer decreased by 5 percent for each year of use. These findings were similar to risk factors for patients using oral contraceptives who did not have the genetic mutation. Understanding the relationship between oral contraceptive use and risk of ovarian cancer can help doctors screen patients for the disease and could even be used as a preventative measure in some cases where a family history of ovarian cancer exists.


Consideration of Hereditary Nonpolyposis Colorectal Cancer in BRCA Mutation-Negative Familial Ovarian Cancer
Cancer, 2009

Stacey A. South, MD, Heidi Vance, MS, Carolyn Farrell, MS, CNP, Richard A. DiCioccio, PhD, Cathy Fahey, BS, M. Steven Piver, MD, and Kerry Rodabaugh, MD

While BRCA mutations are the markers most often associated with breast and ovarian cancer, other mutations can make women more susceptible to developing these and other cancers. A 2009 study using data from the Gilda Radner Familial Ovarian Cancer Registry examined whether a mutation often associated with colorectal cancer may be a reliable marker for determining ovarian cancer risk.
The study examined DNA from these patients, who did not have the BRCA mutation, to determine if any were carriers for a mutation often associated with a certain kind of cancer known as hereditary nonpolyposis colorectal cancer. The mutation is also linked with a higher risk of ovarian cancer, but it is not screened for in patients as often as BRCA mutations.
This study found some link between the presence of the mutation and the risk of ovarian cancer. If this or other mutations eventually are found to be a reliable determination of risk factor, this information could help save lives through increased screening and other early intervention methods.


A genome-wide association study identifies a new ovarian cancer susceptibility locus on 9p22.2
Nature Genetics, 2009

Honglin Song

Women with a first-degree relative diagnosed with ovarian cancer are three times as likely to develop the disease themselves. While much research has been devoted to the genetic markers that are most associated with these cases—namely, BRCA1 and BRCA2 mutations—these known susceptibility genes explain less than half of cases with familial risk.
This large-scale study including data and research from the Gilda Radner Familial Ovarian Cancer Registry used advanced genetic sequencing procedures to examine over 500,000 polymorphisms in 1,800 ovarian cancer cases. This screening helped scientists zero on a small set of mutations that may play a role in the development of the disease, but that had not been studied extensively before this point.
By continuing to examine which genetic alterations may be linked to an increased risk of ovarian cancer, researchers can work toward developing new screening methods to diagnose the disease earlier and give patients their best chance at survival.

Journal of the National Cancer Institute, 2015

Susan J. Ramus et al

We have found strong evidence that deleterious germline mutations in BRIP1 gene are associated with a moderate increase in the risk of epithelial ovarian cancer. Because of the very low frequency of mutations in BARD1 and PALB2 genes, we cannot rule out that these genes also confer susceptibility to ovarian cancer, but NBN mutations do not appear to predispose to ovarian cancer.
These data may have clinical implications for risk prediction and prevention approaches for ovarian cancer in the future if confirmed by other studies, but this study highlights the critical need for accurate risk estimation of candidate susceptibility genes based on very large sample sizes before genes of moderate penetrance have clinical utility in cancer prevention.

Hereditary association between testicular cancer and familial ovarian cancer: A Familial Ovarian Cancer Registry study
Cancer Epidemiology, 2018

John L. Etter et al

Using data from the FOCR, researchers compared the frequency of ovarian cancer among relatives of men with testicular and non-testicular cancers, finding that men with testicular cancer were more likely to have a mother with ovarian cancer than men without the disease. This observation is leading to future investigations of X-linked inheritance, which may elucidate the familial association between testicular and ovarian cancer.

Paternal lineage early onset hereditary ovarian cancers: A Familial Ovarian Cancer Registry study
Plos Genetics, 2018

Kevin H. Eng et al

Our researchers have pursued the hypothesis that the reason an affected woman conveys a higher risk of ovarian cancer to her sister than to her mother is because the risk comes from her paternal grandmother via her father. The investigation examined 892 grandmother/granddaughter pairs from the more than 3,400 such pairs in the FOCR, finding that ovarian cancer rates in both paternal and maternal grandmother/granddaughter pairs were consistent with an X-linked dominant model of inheritance. Our researchers were also able to demonstrate that a genetic locus (position) on the X-chromosome contributes to ovarian cancer risk, acting independently of BRCA1 and BRCA2. These conclusions support the position that women who have affected paternal grandmothers or have affected sisters have increased risk for ovarian cancer.