Author ORCID Identifier
https://orcid.org/0000-0002-1799-238X
Date of Graduation
5-2021
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
Abstract
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.
Keywords
hematologic malignancy, HBOC, therapy-related myeloid neoplasms, leukemia, lymphoma, VR