Four new genes confirmed to increase familial breast cancer risk

Four new genes have been added to those already known to increase the risk of familial breast cancer. Although BRCA1 and BRCA2 are the most well-known inherited breast cancer genes, there are many more, and researchers from the University of Utah’s Huntsman Cancer Institute (HCI) have added four more to that list. “BRCA1 and BRCA2 aren’t the whole story when it comes to inherited breast cancer risk,” said Sean Tavtigian, professor in the Department of Oncological Studies. “We’ve known for a long time that more genes had to be responsible and several have since been discovered. Work published in Cancer Discovery focussed on RINT1, which was not considered a human cancer susceptibility gene. However, researchers discovered that there was at two- to three-fold increase in risk for breast cancer in families that carry a mutation in that gene, said Tavtigian. RINT1 was also found to increase the risk of a broad range of gastrointestinal and gynaecological cancers in these families. “Many genes responsible for a strong increase in cancer risk at one or two sites in the body are also connected with lesser increases in risk at other sites,” said David Goldgar, HCI investigator and joint principal investigator. “However, with RINT1 mutations, the increased risk for other cancers is about equal to that for breast cancer.” A second study published in Breast Cancer Research confirmed MRE11A, RAD50 and NBN were also confirmed to increase the risk of breast cancer. “The proteins encoded by these three genes for a tight complex that is involved in DNA repair, and the three genes had been considered likely candidates,” said Tavtigian. “Interestingly RINT1’s name is an abbreviation for RAD50 Inhibitor 1 and it’s just step downstream from the MRE11A, RAD50 and NBN in a biochemical sense. But we don’t know yet if that biochemical connection explains RINT1’s cancer susceptibility role.” Almost 50% of the familial risk for breast cancer can be explained by a group of rare mutations in known breast cancer susceptibility genes and more common genetic variation in 75 area of the genome each associated with only a small increase in risk. Rare mutations in RINT1 predispose carriers to breast and Lynch Syndrome-spectrum cancers Rare key functional domain missense substitutions in MRE11A, RAD50, and NBN contribute to breast cancer susceptibility: results from a Breast Cancer Family Registry case-control mutation-screening study