Spectrum and Incidence of Primary and Therapy-Related Hematologic Malignancies In Individuals With Brca1 and Brca2 Pathogenic Variants

<p>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 <em>BRCA1</em> and <em>BRCA2</em> 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 <em>BRCA1/2</em> P/LP variants may be more susceptible to developing primary hematologic malignancies. We reviewed medical records of 706 individuals with <em>BRCA1/2</em> 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 <em>BRCA1</em> P/LP variants and 42% had <em>BRCA2</em> 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 <em>BRCA1/2</em> P/LP variants increase the risk of t-MNs.</p>

Name thesis:degree_name

Masters of Science (MS)

Level thesis:degree_level

Thesis (MS)

Year dc:date.available

2021

Authors dc:creator

• Rogers, Rosemary
• <p>https://orcid.org/0000-0002-1799-238X</p>

Contributors dc:contributor

• Courtney DiNardo, MD, MSCE
• Sarah Bannon, MS, CGC
• S. Shahrukh Hashmi, MD, PhD, MPH

• hematologic malignancy
• HBOC
• therapy-related myeloid neoplasms
• leukemia
• lymphoma
• VR
• Genetics and Genomics
• Medicine and Health Sciences

Repository record dc:identifier

https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1097

OAI identifier oai:identifier

oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-2153