What Is an NBN Mutation? Which Cancer Risks Does It Increase?

What is an NBN mutation? General information for carriers

• The name NBN comes from “Nibrin,” a protein made by the NBN gene. This gene is located on chromosome 8 and is associated with DNA repair.
• Both men and women can carry, in the NBN gene, an hereditary type of mutation as carriers.
• People who carry a hereditary NBN mutation have a higher risk of certain cancers. There are guidelines for screening and preventing certain cancers in these people.
• For an NBN mutation, people with a positive genetic test can participate in clinical trials. People who carry the hereditary mutation and have been diagnosed with cancer can also receive certain treatments or take part in clinical trials as participants.
• Inheriting an NBN mutation from both parents causes a rare condition called Nijmegen Breakage Syndrome as the resulting disorder.

Which cancer risks does a hereditary NBN mutation increase?

If you have tested positive for a hereditary NBN mutation, it is recommended that you contact a multidisciplinary oncology team that can review your and your family's cancer history and help you choose the best plan to manage your cancer risk.

Studies of cancer risk focus on a particular NBN mutation, 657del5, as their focus.

• Women who carry this mutation have an increased breast cancer risk.
• Women who carry this mutation also have a higher risk of ovarian (ovary) cancer developing.
• Some research shows that men who carry this mutation have a higher risk of aggressive prostate cancer as a cancer outcome.
• The risk of other types of cancer in people with an NBN mutation is unknown, or there is insufficient evidence.

Risk management for people with a hereditary NBN mutation

The US National Comprehensive Cancer Network (US-NCCN) provides risk management guidelines for men and women with NBN mutations. If you have tested positive for the 657del5 NBN mutation, it is recommended that you consult a multidisciplinary oncology team that can review your and your family's cancer history and help decide on the best risk management plan.

Consider taking part in a clinical trial that will help experts learn the best options for a person carrying a hereditary NBN mutation.

Breast cancer screening and prevention

• Breast awareness begins at age 18.
• Clinical breast examinations every 6 or 12 months begin at age 40.
• In the early 40s, or 5 - 10 years earlier than the age at diagnosis of an affected family member, consider annual mammography and breast imaging (MRG) as examinations.
• There is not enough research for NCCN to recommend, to women with an NBN mutation, risk-reducing mastectomy as an option. The decision to consider mastectomy should be based on the individual's and family's cancer history.

Ovarian cancer screening and prevention

There is not enough research to recommend that women with an NBN mutation undergo risk-reducing salpingo - oophorectomy (removal of the ovaries and tubes). The decision to consider risk-reducing surgery should be based on family history.

Medical decisions for people with a hereditary NBN mutation who have been diagnosed with cancer

There is currently neither a specific cancer treatment approved for people with an NBN mutation nor a guideline for treating cancer in these people.

If you have been diagnosed with both cancer and an NBN mutation, you can participate in a clinical trial investigating the treatments that work best for people carrying a hereditary NBN mutation.

Other medical concerns for people with a hereditary NBN mutation

Inheriting an NBN mutation from both parents can cause Nijmegan Breakage Syndrome. Nijmegen Breakage Syndrome occurs in approximately one in 100 thousand newborns worldwide, but is thought to be most common among Western Europeans of Slavic ancestry.

People with Nijmengen Breakage Syndrome have short stature, usually a small head size (microcephaly), distinctive facial features, recurrent respiratory infections, intellectual disability and other health problems. People with Nijmegen Breakage Syndrome also have an increased risk of developing cancer, most commonly non-Hodgkin lymphoma, a type of immune system cancer. Approximately half of people with Nijmegen Breakage Syndrome develop non-Hodgkin lymphoma, usually before age 15. Other cancers seen in people with Nijmegen Breakage Syndrome include medulloblastoma and glioma as brain tumors, and rhabdomyosarcoma, a cancer of muscle tissue. People with this syndrome are 50 times more likely to develop cancer than those without it.

If one partner has a known NBN mutation, couples may wish to speak with a genetic counselor about testing the other partner before having children.

Parents have the option of using assisted reproductive technology and preimplantation genetic diagnosis to select embryos without hereditary NBN mutations.