Homologous Recombination Repair Genetics (HRR genes)

Mutations in BRCA1 and BRCA2 greatly increase the risk of breast, ovarian, and pancreatic cancers. The two genes are part of a biochemical pathway that uses homologous recombination to repair DNA double strand breaks (homologous recombination repair, HRR). Similar to their well known counterparts, many other genes in the HRR pathway are either confirmed or suspected cancer susceptibility genes for one or more of the trio of cancers (breast, ovarian and pancreatic cancers).

These observations led Sean Tavtigian, PhD, and Leigh Neumayer,MD, to hypothesize the existence of a multi-cancer syndrome caused by an inherited defect in almost any one of the central HRR pathway genes: the “HRR-syndrome”. To address this hypothesis, the investigators will analyze the frequency, penetrance and spectrum of tumors conferred by heterozygous inheritance of a mutation in one of the HRR genes (excluding BRCA1 and BRCA2).

In this project, 200 individuals diagnosed with pancreatic, ovarian, or breast cancer will be sequenced using a panel of 30 known cancer genes, including HRR genes, to determine how often the genetic cause can be explained. For those with a genetic mutation, their family will be studied to characterize cancer risks associated with these genes, and to develop accurate screening and prevention strategies.

breast, ovarian, pancreatic cancers

DNA Homologous Recombination Repair Pathway (HRR). Mutations in many genes in the HRR pathway are either known or suspected to predispose patients to cancer.