| 36 37 | See page 67 for references Cancer risks · ·While the exact cancer risk is unknown, women with NBN mutations may have a lifetime breast cancer risk of up to 30%, compared with the general population risk of 12%. Most research to date has come from one European founder mutation, c.657del5. · ·Although NBN mutations have been reported in patients with other types of cancer, such as prostate and ovarian cancer, more research is needed to determine the exact associated cancer types and possible risks. Potential management options Management guidelines for NBN mutations are evolving. A thorough review of family history is important to better understand cancer risks and develop an individualized screening plan. For women with NBN mutations, NCCN recommends the following: · ·Annual mammogram with consideration of tomosynthesis and consideration of breast MRI beginning at age 40 or ten years before the youngest breast cancer diagnosis in the family. · ·Additional risk-reduction strategies, such as prophylactic mastectomy or the use of medication, may also be considered on an individualized basis (e.g. based on family history), but are not routinely recommended at this time. Of note, current management recommendations are based on data for the c.657del5 truncating founder mutation. Limited data exists on other types of mutations, however patients with other truncating mutations should be managed similarly to those with the c.657del5 founder mutation. As discussed above, in rare instances an individual may inherit two mutations in NBN, one from each parent. This has the potential to result in a rare condition called Nijmegen breakage syndrome. For individuals who test positive for NBN, it may be appropriate to consider carrier screening for NBN mutations in their spouse/partner. NBN gene summary NBN-associated hereditary cancer Gene name NBN Associated syndrome NBN-associated hereditary cancer Primary associated cancers Breast Frequency Varies by ethnicity; as high as 1 in 155 in Slavic populations Inheritance pattern Autosomal dominant Overview · ·NBN is a gene associated with a moderate risk of breast cancer. · ·Because NBN mutations do not always explain all of the cancer risk in a family, family members who test negative for a known familial NBN mutation may still be at increased risk for cancer based on the family history. · ·Cancer risks associated with mutations in NBN vary and are influenced by family history, as well as the specific mutation identified. · ·Individuals who inherit an NBN mutation from both parents are at risk for Nijmegen breakage syndrome. For individuals who test positive for a mutation in NBN, it may be appropriate to consider carrier screening for NBN mutations in their spouse/partner. About NBN NBN was initially identified in individuals affected with Nijmegen breakage syndrome, an autosomal recessive condition associated with an increased risk for early-onset cancer and lung and sinus infections. Studies of Czech families affected with the condition later identified a potentially increased risk for several types of cancer associated with the Eastern European founder mutation c.657del5. Additional research has focused on the risk of breast cancer associated with NBN mutations, with conflicting results.