BRIP1

 

BRIP1-Related Cancer Risk

The BRIP1 gene is classified as a “moderate risk” gene, meaning that there is a modestly increased risk for certain types of cancers.  For example, women who have one BRIP1 pathogenic gene mutation have an increased risk for ovarian cancer as compared to the general population.  Data regarding a potential association between BRIP1 gene mutations and breast cancer risk have been inconsistent, but overall there appears to not be an increased risk for breast cancer.  Further research is needed to understand the interactions of moderate risk genes and family history on lifetime cancer risk.

Rarely, an individual will inherit two BRIP1 gene mutations – one from each parent.  When this happens, the child has a severe disease called Fanconi Anemia (FA).  Children who have FA have blood problems, developmental issues, and increased risk of cancers such as leukemia and lymphoma.

 

BRIP1 cancer screening and risk-reducing options

The BRIP1 gene is classified as a “moderate risk” gene, meaning that there is a modestly increased risk for certain types of cancers.  For example, women who have one BRIP1 pathogenic gene mutation have an increased risk for ovarian cancer as compared to the general population.  Data regarding a potential association between BRIP1 gene mutations and breast cancer risk have been inconsistent, but overall there appears to not be an increased risk for breast cancer.  Further research is needed to understand the interactions of moderate risk genes and family history on lifetime cancer risk.

Rarely, an individual will inherit two BRIP1 gene mutations – one from each parent.  When this happens, the child has a severe disease called Fanconi Anemia (FA).  Children who have FA have blood problems, developmental issues, and increased risk of cancers such as leukemia and lymphoma.

 

BRIP1 associated therapeutic/ treatment implications

Individuals who have a cancer diagnosis and an identified BRIP1 pathogenic mutation should speak with their treating physician about the availability of targeted/ personalized treatment options.

Clinical trials evaluating different medications in individuals who have pathogenic mutations in BRIP1 and/or other related genes might be available now or in the future.

 

BRIP1 testing in other family members

At this point in time, testing adult family members for a moderate risk gene mutation does NOT provide the same clarity or guidance that testing for a high risk gene mutation does. This is because moderate risk gene mutations should not be assumed to be the sole explanation for a particular family’s history of cancer.  For example, a family could have additional unidentified genetic and/or non-genetic risk factors contributing to the development of cancer seen in family members.  It is recommended that family members discuss risks, benefits and limitations of genetic testing with their physician and/or genetic counselor.  If an adult family member were to test positive for the familial BRIP1 gene mutation, increased cancer screening might be considered.  However, given the current lack of data regarding BRIP1 gene mutations, if an adult family member were to test negative for a familial BRIP1 gene mutation, that individual may still be at increased risk for cancer depending upon the family history and possibility for other genes to be playing a role.  Cancer screening should be performed in accordance with the family history until further data is available.

Because of the potential risk for children to be affected with Fanconi Anemia if both of their parents have BRIP1 gene mutations, family members who are considering having children should speak with a genetic counselor to discuss risks and the possibility of having their partner tested before conceiving.  Genetic test results may be used by some individuals for reproductive decision-making including the use of pre-implantation genetic diagnosis (PGD), donor gametes, or adoption.

 

Future considerations

As research and data on cancer risk estimates continue to evolve, physicians and researchers will gain a better understanding of how a BRIP1 gene mutation influences medical care.  Because the information provided to patients will almost certainly change, those with a BRIP1 gene mutation are encouraged to keep in touch with their medical providers in order to receive updates.

 

References:

  1. Tung N, Domchek SM, Stadler Z, Nathanson KL, Couch F, Garber JE, et al. Counselling framework for moderate-penetrance cancer-susceptibility mutations. Nat Rev Clin Oncol. 2016;13(9):581-8. doi: 10.1038/nrclinonc.2016.90. PubMed PMID: 27296296.
  2. Pritchard CC, Mateo J, Walsh MF, et al: Inherited DNA-Repair Gene Mutations in Men with Metastatic Prostate Cancer. N Engl J Med 375:443-53, 2016
  3. Walsh MF, Nathanson KL, Couch FJ, Offit Adv Exp Med Biol. 2016;882:1-32. Genomic Biomarkers for Breast Cancer Risk. doi: 10.1007/978-3-319-22909-6
  4. Norquist BM, Harrell MI, Brady MF, et al. Inherited mutations in women with ovarian carcinoma. JAMA Oncol 2015;2:1–9.
  5. Ramus SJ, Song H, Dicks E, et al. Germline mutations in the BRIP1, BARD1, PALB2, and NBN genes in women with ovarian cancer. J Natl Cancer Inst 2015;107:pii: djv214.
  6. Rafnar T, Gudbjartsson DF, Sulem P, et al. Mutations in BRIP1 confer high risk of ovarian cancer. Nat Genet 2011;43:1104–1107.
  7. Fleming GF, Seidman J, Lengyel E. Epithelial ovarian cancer. In: Barakat RR, Markman M, Randall ME, eds. Principles and Practice of Gynecologic Oncology, 6th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2013:757–847.
  8. Easton DF, Lesueur F, Decker B, et al. No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: implications for gene panel testing. J Med Genet 2016;53:298–309.