Abstract
BACKGROUND: The HOXB13 gene has been associated with hereditary prostate cancer (PCa), with rare germline variants linked to early-onset and aggressive forms of the disease. While the G84E variant has been well-characterized in Caucasian populations, the clinical relevance of the X285K variant-primarily found in individuals of African ancestry-remains unclear. This study aimed to determine the prevalence of HOXB13 X285K in a French Caribbean cohort and explore its association with adverse clinical features. METHODS: We conducted a prospective cohort study including 465 men diagnosed with prostate cancer. Germline sequencing of HOXB13 was performed using Sanger methodology to identify the presence of the X285K variant. RESULTS: The HOXB13 X285K variant was identified in 5 patients (1.07%). All carriers had clinically significant disease. Among them, three presented with de novo metastatic prostate cancer, and two with intermediate-risk localized disease experienced early biochemical recurrence (at 22 and 34 months). In contrast, recurrence-free survival exceeded 85% at 50 months in the overall cohort. CONCLUSIONS: Although limited by small sample size, these findings suggest a possible link between the HOXB13 X285K variant and early tumor progression. This highlights the importance of screening for this rare variant, particularly in patients of African descent who are underrepresented in genomic studies, to support improved risk stratification and personalized management.