Confirmation of the HOXB13 G84E germline mutation in familial prostate cancer.
BACKGROUND
A recent study of familial and early onset prostate cancer reported a recurrent rare germline mutation of HOXB13 among men of European descent. The gene resides within the 17q21 hereditary prostate cancer linkage interval.


METHODS
We evaluated the G84E germline mutation (rs138213197) of HOXB13 in a case-control study of familial prostate cancer at Vanderbilt University (Nashville, TN) to independently evaluate the association of the mutation with familial prostate cancer. We genotyped 928 familial prostate cancer probands and 930 control probands without a personal or family history of prostate cancer.


RESULTS
Our study confirmed the association between the G84E mutation of HOXB13 and risk of prostate cancer among subjects of European descent. We observed the mutation in 16 familial cases and in two controls, each as heterozygotes. The odds ratio (OR) for prostate cancer was 7.9 [95% confidence interval, (CI) 1.8-34.5, P = 0.0062] among carriers of the mutation. The carrier rate was 1.9% among all familial case probands and 2.7% among probands of pedigrees with ≥3 affected. In a separate case series of 268 probands of European descent with no additional family history of prostate cancer, the carrier rate was 1.5%.


CONCLUSIONS
The germline mutation G84E of HOXB13 is a rare but recurrent mutation associated with elevated risk of prostate cancer in men of European descent, with an effect size that is greater than observed for previously validated risk variants of genome wide association studies.


CONCLUSIONS
This study independently confirms the association of a germline HOXB13 mutation with familial prostate cancer.
Department of Medicine, Vanderbilt- Ingram Cancer Center, Vanderbilt University School of Medicine Nashville, TN 37232, USA.
Joan P
JP
Breyer
T Grant
TG
Avritt
Kate M
KM
McReynolds
William D
WD
Dupont
Jeffrey R
JR
Smith
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018095:Germ-Line Mutation; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000235:genetics*; D018570:Risk Assessment
C484414:HOXB13 protein, human; D018398:Homeodomain Proteins