Author ORCID Identifier

Date of Graduation


Document Type

Thesis (MS)

Program Affiliation

Genetic Counseling

Degree Name

Masters of Science (MS)

Advisor/Committee Chair

Courtney DiNardo, MD, MSCE

Committee Member

Sarah Bannon, MS, CGC

Committee Member

S. Shahrukh Hashmi, MD, PhD, MPH

Committee Member

Laura Farach, MD

Committee Member

Maureen Mork, MS, CGC

Committee Member

Banu Arun, MD


Therapy-related myeloid neoplasms (t-MN) are rare and deadly hematologic malignancies that develop following exposure to cytotoxic therapies such as radiation, chemotherapy, and poly (adenosine diphosphate-ribose)-ADP polymerase (PARP) inhibitors. Preliminary evidence suggests that germline BRCA1 and BRCA2 pathogenic and likely pathogenic (P/LP) variants may increase susceptibility to t-MNs due to the genes’ established role in DNA damage response. There is also evidence that individuals with BRCA1/2 P/LP variants may be more susceptible to developing primary hematologic malignancies. We reviewed medical records of 706 individuals with BRCA1/2 P/LP variants to assess hematologic malignancy diagnoses and t-MN development. Our study population was 5.1% male and 94.9% female, 58% had BRCA1 P/LP variants and 42% had BRCA2 P/LP variants, and the majority (59.92%) identified as Caucasian. Twenty-one hematologic malignancies were identified (2.97%): non-Hodgkin lymphoma in 9/706 individuals (1.27%), chronic myeloid leukemia and multiple myeloma each in 2/706 individuals (0.28%), respectively, and acute myeloid leukemia, unspecified leukemia, and Hodgkin lymphoma each in 1/706 individuals (0.14%). Therapy-related myeloid neoplasms were seen in 5/706 individuals (0.71%), a significantly higher incidence than 0.13/100,000 (0.0013%) observed in the general population (p-value: 0.000001). The estimated 20-year risk of t-MN development is 2.11% (95% CI 0.74 – 5.96). This study supports the assertation that germline BRCA1/2 P/LP variants increase the risk of t-MNs.


hematologic malignancy, HBOC, therapy-related myeloid neoplasms, leukemia, lymphoma, VR



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