Abstract
Prostate cancer (PCa) is one of the most common malignancies among men worldwide. Its etiology is multifactorial, but genetic variations play a critical role in disease development and progression, particularly mutations in BRCA1/2, HOXB13, ATM, CHEK2, and TP53. In Ukraine, PCa ranks as the second leading cause of cancer-related death and the most frequently diagnosed malignancy in males.
A systematic search on PubMed, MEDLINE, Embase, Web of Science, Google Scholar, and CENTRAL (up to April 19, 2025) was conducted without language or date restrictions to identify studies on prostate cancer in adults (≥18 years) carrying HOXB13 and TP53 mutations, excluding other cancer types.
A 68-year-old Ukrainian male presented in January 2020 with urinary symptoms and back pain. Digital rectal examination revealed an enlarged prostate with nodules. Biopsy confirmed acinar adenocarcinoma, Gleason score 8 (4+4). CT showed stage T4N1M1 disease with bone and retroperitoneal lymph node metastases. Family history revealed paternal lymphoma at the age of 71. Blood genetic testing identified HOXB13 c.251G>A (p.Gly84Glu) and TP53 c.581T>G (p.Leu194Arg) mutations. Over four years, the patient underwent orchiectomy, hormonal therapy, radiation and chemotherapy, but died of progressive PCa at the age of 72, 57 months after diagnosis.
The coexistence of HOXB13 and TP53 mutations likely contributed to the aggressive tumor phenotype. HOXB13 variants are linked to hereditary and early-onset PCa, while TP53 mutations promote progression and therapy resistance. This case highlights the clinical value of genetic testing in aggressive prostate cancer and underscores the need for research into targeted therapies for genetically predisposed patients.