Scientists Search Ovarian Cancer Registry for Disease-Related Gene Link

Roswell Park genetic scientists are currently investigating two genes implicated in ovarian cancer to better understand their involvement in other types of cancer.

According to Lara Sucheston, PhD, Assistant Professor, Biostatistics and Oncology at Roswell Park, the “effect-modifier” genes are bits of DNA that, rather than directly causing health problems, influence the behavior of recognized, disease-related genes.  

Many cases of inherited breast and ovarian cancer involve alterations in two genes, designated BRCA1 and BRCA2 (for breast cancer 1 and breast cancer 2). “But why do BRCA1 and BRCA2 mutations show up in less than half of all families with two or more ovarian cancer cases among first-degree relatives?” Sucheston asks. “Conversely, why do only some who inherit these genes develop cancer—and why do some develop breast cancer, but not ovarian cancer? What protects them from ovarian cancer?”

One likely explanation is the presence of effect modifier genes, which may be either contributing to, or blocking the effects of genes like BRCA1 and BRCA2.

Sucheston—with funding from a grant from Roswell donations—is working closely with investigators and clinicians, including Drs. Kunle Odunsi and Shashikant Lele of RPCI’s Department of Gynecologic Oncology, to analyze 13,000 DNA sequences and supporting cancer-history documentation from the Gilda Radner Familial Ovarian Cancer Registry. The Registry, led by Dr. Lele and housed at Roswell Park, is the world’s largest collection of family histories, medical records, and blood samples from ovarian cancer patients and their family members.

“Developing safe, effective cancer treatments is profoundly difficult,” says Dr. Sucheston. “Modifier genes represent a potentially powerful alternative. Once their mechanisms are understood, perhaps they can be harnessed to prevent or treat disease.”