Pathogenic variants (disease-causing) in the HOXB13 gene are linked to an increased risk of prostate cancer. There is a common pathogenic variant, known as G84E, which is most often reported in men of Northern European ancestry. This variant has also been preliminarily associated with bladder cancer, kidney cancer, non-Hodgkin’s lymphoma, and breast cancer; however, exact risk estimates are unknown due to its rarity. Further, associations with these cancers need to be confirmed. Management of HOXB13–related prostate cancer risk includes regular surveillance tailored to guidelines to detect tumors early. HOXB13 variants are not known to be more common in the Ashkenazi Jewish population.
Pathogenic variants in HOXB13 exhibit autosomal dominant inheritance. This means there is a 50% chance the condition can be passed from generation-to-generation. First degree relatives (parents, siblings, children) have a 50% chance to have the same pathogenic variant whereas second degree relatives (grandparents, aunts/uncles, nieces/nephews, half-siblings) have a 25% chance. More distant relatives have lower chances of having the same pathogenic variant when one is identified in the family.
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Written December 2025
