The HOXB13 variant X285K is associated with clinical significance and early age at diagnosis in African American prostate cancer patients.

Background: Recently, a novel HOXB13 variant (X285K) was observed in men of African descent with prostate cancer (PCa) in Martinique. Little is known about this or other variants in HOXB13 which may play a role in PCa susceptibility in African-American (AA) men.

Methods: We sequenced HOXB13 in an AA population of 1048 men undergoing surgical treatment for PCa at Johns Hopkins Hospital.

Results: Seven non-synonymous germline variants were observed in the patient population. While six of these variants were seen only once, X285K was found in eight patients. In a case-case analysis, we find that carriers of this latter variant are at increased risk of clinically significant PCa (1.2% carrier rate in Gleason Score ≥7 PCa vs. 0% in Gleason Score <7 PCa, odds ratio, OR = inf; 95% Confidence Interval, 95%CI:1.05-inf, P = 0.028), as well as PCa with early age at diagnosis (2.4% carrier rate in patients <50 year vs. 0.5% carrier rate in patients ≥50 year, OR = 5.25, 95% CI:1.00-28.52, P = 0.03).

Conclusions: While this variant is rare in the AA population (~0.2% MAF), its ancestry-specific occurrence and apparent preferential association with risk for the more aggressive disease at an early age emphasizes its translational potential as an important, novel PCa susceptibility marker in the high-risk AA population.