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NBN gene
Associated Syndrome Name: NBN-associated Cancer Risk
NBN Summary Cancer Risk Table
CANCER
GENETIC CANCER
RISK
Female Breast Elevated Risk
Prostate
Elevated Risk
NBN gene Overview
NBN-associated Cancer Risk
1, 2, 3, 4, 5
Women with NBN mutations have a risk for breast cancer that is thought to be increased over the 12.5%
lifetime risk for women in the general population of the United States.
Men with mutations in the NBN gene are thought to have an increased risk for prostate cancer.
NBN mutations are most common in patients of Slavic ancestry, where a single founder mutation
(c.657_661del) is estimated to be present in 1:167 individuals. Current female breast cancer and male
prostate cancer risk estimates are based primarily on studies of individuals of Eastern European ancestry
with this specific mutation, and may not apply to other NBN mutations or patients of other ancestries.
It has been suggested that patients with NBN mutations have an increased risk for cancers other than
breast and prostate cancer. In particular, there is evidence for an association with pediatric leukemias and
lymphomas. The data for this are not conclusive at this time and there are no current medical
management recommendations associated with pediatric cancer risk for carriers of NBN mutations.
Currently there are no widely accepted guidelines for the medical management of men and women with
NBN mutations. Options based on guidelines for other conditions which moderately increase the risk for the
relevant cancers are listed below. Since information about the cancer risks associated with NBN mutations
is relatively new, and there is uncertainty about the best ways to reduce these risks, it may be appropriate
to interpret these results in consultation with cancer genetics experts in this emerging area of knowledge.
NBN gene Cancer Risk Table
CANCER TYPE
AGE RANGE
Female Breast
To age 80
Prostate
To age 80
1, 2
3, 5
NBN Cancer Risk Management Table
1
CANCER RISK
RISK FOR GENERAL
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POPULATION
Up to 30%
10.2%
Increased risk
13.6%
The overview of medical management options provided is a summary of professional society guidelines as of the last
Myriad update shown on this page. The specific reference provided (e.g., NCCN guidelines) should be consulted for
more details and up-to-date information before developing a treatment plan for a particular patient.
This overview is provided for informational purposes only and does not constitute a recommendation. While the
medical society guidelines summarized herein provide important and useful information, medical management
decisions for any particular patient should be made in consultation between that patient and his or her healthcare
provider and may differ from society guidelines based on a complete understanding of the patient's personal
medical history, surgeries and other treatments.
CANCER
TYPE
Female
Breast
PROCEDURE
AGE TO BEGIN
Breast awareness - Women should be familiar
with their breasts and promptly report changes to
their healthcare provider. Periodic, consistent
breast self-examination (BSE) may facilitate
8
breast awareness.
Individualized
NA
Clinical encounter, including clinical breast exam,
ongoing risk assessment and risk reduction
8
counseling
When genetic risk is
identified
Every 6 to 12
months
Mammography and consideration of breast MRI
7
with contrast
Age 40, or modified to a
younger age based on the
family history of breast
cancer
Annually
Consider additional risk-reduction strategies.
Individualized
NA
Start risk and benefit discussion about offering
baseline digital rectal examination (DRE) and
Prostate Specific Antigen (PSA), incorporating
9
information about increased prostate cancer risk.
45 years
Individualized
7, 8
Prostate
FREQUENCY
Information for Family Members
The following information for Family Members will appear as part of the MMT for a patient found to have a mutation
in the NBN gene.
A major potential benefit of myRisk genetic testing for hereditary cancer risk is the opportunity to prevent cancer in
relatives of patients in whom clinically significant mutations are identified. Healthcare providers have an important
role in making sure that patients with clinically significant mutations are informed about the risks to relatives, and
ways in which genetic testing can guide lifesaving interventions.
In rare instances, an individual may inherit mutations in both copies of the NBN gene, leading to the condition
Nijmegen Breakage Syndrome (NBS). Individuals with NBS will have growth retardation, immunodeficiency, and a
greatly increased risk for varied types of cancer diagnosed at young ages. The children of this patient are at risk of
inheriting NBS only if the other parent is also a carrier of an NBN mutation. Screening the spouse/partner of this
patient for NBN mutations may be appropriate, particularly if they are of Eastern European ancestry, since NBN
4
mutations are more common in this group.
2
References
1. Steffen J, et al. Germline mutations 657del5 of the NBS1 gene contribute significantly to the incidence of
breast cancer in Central Poland. Int J Cancer. 2006 119:472-5. PMID: 16770759.
2. Zhang B, et al. Genetic variants associated with breast-cancer risk: comprehensive research synopsis, metaanalysis, and epidemiological evidence. Lancet Oncol. 2011 12:477-88. PMID: 21514219.
3. Cybulski C, et al. An inherited NBN mutation is associated with poor prognosis prostate cancer. Br J Cancer.
2013 108:461-8. PMID: 23149842.
4. Varon R, et al. Nijmegen Breakage Syndrome. 2014 May 08. In: Pagon RA, et al., editors. GeneReviews®
[Internet]. Available from http://www.ncbi.nlm.nih.gov/books/NBK1176/ PMID: 20301355.
5. Cybulski C, et al. NBS1 is a prostate cancer susceptibility gene. Cancer Res. 2004 64:1215-9. PMID: 14973119.
6. Surveillance Research Program, National Cancer Institute SEER*Stat software (seer.cancer.gov/seerstat) V
8.0.1, Nov 19, 2012.
7. Daly M et al. NCCN Clinical Practice Guidelines in Oncology®: Genetic/Familial High-Risk Assessment: Breast
and Ovarian. V 1.2017. September 19. Available at http://www.nccn.org.
8. Bevers TB, et al. NCCN Clinical Practice Guidelines in Oncology®: Breast Cancer Screening and Diagnosis. V
1.2016. July 27. Available at http://www.nccn.org.
9. Carroll PR et al. NCCN Clinical Practice Guidelines in Oncology®: Prostate Cancer Early Detection. V 2.2016.
April 28. Available at http://www.nccn.org.
Last Updated on 10-Jan-2017
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