Researchers at Huntsman Cancer Institute at the University of Utah have discovered four new genes that increase breast cancer risk when mutated.
The team, who lead an international consortium with the aim of locating more gene mutations that may cause inherited breast cancer susceptibilities, have added RINT1, MRE11A, RAD50 and NBN to the growing list of higher risk genes.
Before a cell becomes cancerous, a number of mistakes need to be present in its genetic code. These mistakes are referred to as mutations.
It is possible to be born with a gene mutation that may increase the risk of cancer. This mutation does not mean the individual will categorically suffer from a form of cancer, but the individual will be more likely to develop cancer than the average person.
Inherited cases of breast cancer are usually associated with two abnormal genes: BRCA1 and BRCA2.
BRCA1 and BRACA2 genes are present in everyone. Their functions are to repair cell damage and ensure normal growth of breast cells. Women, who have an abnormal BRCA1 or BRCA2 gene, and diagnosis of breast cancer, often have a family history of breast cancer, ovarian cancer and other cancers.
These two gene mutations account for about 20-25% of hereditary breast cancers – caused by abnormal genes passed from parent to child – and about 5-10% of all breast cancers.
BRCA1 and BRCA2 gene mutations are not alone
According to study investigator Sean Tavtigian, PhD, a Huntsman Cancer Institute investigator and professor in the Department of Oncological Sciences at the University of Utah (U of U):
“BRCA1 and BRCA2 aren’t the whole story when it comes to inherited breast cancer risk. We’ve known for a long time that more genes had to be responsible, and several have since been discovered, by us and others. Originally, the gene we are currently studying, called RINT1, was not considered a human cancer susceptibility gene. But then we discovered there was a two- to three-fold increase in risk for breast cancer in families that carry a mutation in that gene.”
Two studies were involved in the research; RINT1 findings were published online in May in the journal Cancer Discovery, and MRE11A, RAD50 and NBN findings were published at the beginning of this month by the journal Breast Cancer Research.
There are three classes of breast cancer susceptibility genes recognized as high-risk: BRCA1 and BRCA2, intermediate-risk genes – such as ATM and CHEK2 – and modest-risk SNPs. Data have established that MRE11A, RAD50 and NBN are intermediate-risk breast cancer susceptibility genes.
“The proteins encoded by these three genes form a tight complex that is involved in DNA repair, and the three genes had been considered likely candidates. Interestingly, RINT1’s name is an abbreviation for ‘RAD50 Interactor 1,’ and it’s just one step downstream from the MRE11A, RAD50 and NBN complex in a biochemical sense. But we don’t know yet if that biochemical connection explains RINT1’s cancer susceptibility role.”
RINT1 was detected to additionally increase risk for a broad spectrum of gastrointestinal and gynecological cancers in families that carry the gene mutation.
“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,” reveals David Goldgar, PhD, professor in the Department of Dermatology at the U of U, an HCI investigator, and another of the study’s joint-principal investigators. “However, with RINT1 mutations, the increased risk for other cancers is about equal to that for breast cancer.”
Breast cancer susceptibility genes, which now include RINT1, MRE11A, RAD50 and NBN, account for almost 50% of the familial risk of breast cancer, compared with 5 years ago.