Gene Mutation Implicated in Heightened Breast Cancer Risk in Some FamiliesAn inherited mutation in the Abraxas gene, which encodes a protein that interacts with BRCA1 and other DNA-repair proteins, is associated with an increased risk of breast cancer in some families, new study results show. The findings were published February 22 in Science Translational Medicine.
Inherited mutations in BRCA1 and BRCA2 are the strongest known genetic risk factors for breast and ovarian cancer, but these mutations do not account for all familial breast cancers worldwide.
To determine whether mutations in Abraxas might influence breast cancer risk, a team of Finnish and U.S. researchers screened breast cancer patients from 125 Northern Finnish families with a history of breast cancer for hereditary mutations in the Abraxas gene. Several gene-sequence variants were found, one of which was likely to result in altered protein function.
Three of the families were found to carry this mutation, as did one additional woman from an unselected group of breast cancer patients who turned out to have a family history of the disease. In the two families in which this analysis could be performed, the mutation was found to occur together with breast cancer. The researchers did not find the Abraxas mutation in 868 healthy Northern Finnish women.
The Abraxas protein binds directly to the BRCA1 protein and is responsible for delivering BRCA1 to sites of DNA damage in the cell nucleus, explained Dr. Roger Greenberg of the University of Pennsylvania, a co-author of the study with Dr. Robert Winqvist of the University of Oulu in Finland. “The mutant protein still interacted with BRCA1 and other DNA-repair proteins but prevented them from getting to DNA damage sites,” Dr. Greenberg said.
Defects in the DNA repair process lead to changes in a cell’s genetic material that can increase the risk of breast cancer and other cancers. Indeed, the researchers found several cancer types besides breast cancer in two of the families with Abraxas mutations, suggesting that the gene may play a role in other cancers, as does the BRCA1 gene.
Because the study looked only at people in Northern Finland, “it will be important…to investigate Abraxas mutations in other populations,” Dr. Greenberg said. Eventually, he added, Abraxas could be one of several genes tested for mutations in families with a history of breast and ovarian cancer.
Furthermore, noted Dr. Richard Pelroy of NCI’s Division of Cancer Biology, the information gleaned on how Abraxas works in concert with BRCA1 could aid development of treatments that target BRCA1 defects.