RAD51D gene

Associated Syndrome Name: RAD51D-associated Cancer Risk (Women only)

RAD51D Summary Cancer Risk Table

Cancer Genetic Cancer Risk
OvarianHigh Risk
BreastElevated Risk

RAD51D gene Overview

RAD51D-associated Cancer Risk (Women only) 1, 2, 3, 4, 5, 6, 7, 8, 9
  • Women with RAD51D mutations have an increased risk for ovarian cancer.
  • Women with RAD51D mutations may have only a small increased risk for breast cancer overall, but there is a significant increase in the risk for Triple Negative Breast Cancer (TNBC). This type of breast cancer lacks estrogen and progesterone receptors, and does not express Her2. This type of breast cancer can be more aggressive than other types of breast cancer.
  • At this time, there are no known cancer risks for men due to mutations in RAD51D.
  • Although there are high cancer risks for patients with mutations in RAD51D, there are interventions that may be effective at reducing these risks. Guidelines from the National Comprehensive Cancer Network (NCCN) that may apply are listed below. Since information about the cancer risks associated with RAD51D mutations is relatively new, and there is still some 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.

RAD51D gene Cancer Risk Table

Cancer Type Age Range Cancer Risk Risk for General Population
OvarianTo age 505, 102.3%0.2%
To age 805, 9, 1014.8%0.9%
Female BreastTo age 801, 2, 10Elevated risk, with a particularly increased risk for Triple Negative Breast Cancer (TNBC).10.6%

RAD51D Cancer Risk Management Table

The overview of medical management options provided is a summary of professional society guidelines. The most recent version of each guideline should be consulted for more detailed 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 Procedure Age to Begin Frequency
(Unless otherwise indicated by findings)
OvarianConsider bilateral salpingo-oophorectomy (BSO).645 to 50 years, or earlier if there is a family history of ovarian cancer at a younger ageNA
Other than consideration of BSO, currently there are no specific medical management recommendations for ovarian cancer risk in mutation carriers. However, the increase in risk may warrant consideration of individualized ovarian cancer risk-reduction strategies using other currently available options, such as surveillance and the use of risk-reducing agents.6IndividualizedNA
Female BreastCurrently there are no specific medical management guidelines for breast cancer risk in mutation carriers. However, the increased risk for Triple Negative Breast Cancer (TNBC) warrants consideration of individualized breast cancer risk-reduction strategies, such as the modification of standard population screening recommendations by starting screening at younger ages, performing screenings at greater frequency, and utilizing more sensitive technologies such as breast MRI.IndividualizedNA

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 RAD51D gene.

This patient's relatives are at risk for carrying the same mutation(s) and associated cancer risks as this patient. Cancer risks for females and males who have this/these mutation(s) are provided below.

Family members should talk to a healthcare provider about genetic testing. Close relatives such as parents, children, brothers and sisters have the highest chance of having the same mutation(s) as this patient. Other more distant relatives such as cousins, aunts, uncles, and grandparents also have a chance of carrying the same mutation(s). Testing of at-risk relatives can identify those family members with the same mutation(s) who may benefit from surveillance and early intervention.

At this time, there are no known cancer risks for men due to mutations in RAD51D.

References

  1. Shimelis H, et al. Triple-Negative Breast Cancer Risk Genes Identified by Multigene Hereditary Cancer Panel Testing. J Natl Cancer Inst. 2018 110:855-862. PMID: 30099541.
  2. Hall, M et al. 2020 Triple-negative breast cancer risk with pathogenic variants in hereditary cancer predisposition genes. Presented at San Antonio Breast Cancer Symposium 2020.
  3. Breast Cancer Association Consortium, et al. Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women. N Engl J Med. 2021 384:428-439. PMID: 33471991.
  4. Yang X, et a. Ovarian and Breast Cancer Risks Associated With Pathogenic Variants in RAD51C and RAD51D. J Natl Cancer Inst. 2020 112:1242-1250. PMID: 32107557.
  5. Song H, et al. Contribution of Germline Mutations in the RAD51B, RAD51C, and RAD51D Genes to Ovarian Cancer in the Population. J Clin Oncol. 2015 10:2901-7. PMID: 26261251.
  6. Daly M et al. NCCN Clinical Practice Guidelines in Oncology®: Genetic/Familial High-Risk Assessment: Breast, Ovarian and Pancreatic. V 1.2022. Aug 11. Available at https://www.nccn.org.
  7. Thompson ER, et al. Analysis of RAD51D in Ovarian Cancer Patients and Families with a History of Ovarian or Breast Cancer. PLoS One. 2013 8:e54772. PMID: 23372765.
  8. Wickramanyake A, et al. Loss of function germline mutations in RAD51D in women with ovarian carcinoma. Gynecol Oncol. 2012 127:552-5. PMID: 22986143.
  9. Loveday C, et al. Germline mutations in RAD51D confer susceptibility to ovarian cancer. Nat Genet. 2011 43:879-82. PMID: 21822267.
  10. SEER*Explorer: An interactive website for SEER cancer statistics [Internet]. Surveillance Research Program, National Cancer Institute. [Cited 2020 Sep 14]. Available from https://seer.cancer.gov/explorer/.
Last Updated on 21-Apr-2022