Prostate cancer risk allele specific for African descent associates with pathologic stage at prostatectomy.
OBJECTIVE
A region on chromosome 8q24 was recently identified as a novel prostate cancer risk locus. Inherited variation in this region is associated with prostate cancer risk in the general population (21-58%), and specific alleles show a strong association in African-American men. This study was designed to evaluate associations between 8q24 risk alleles and clinical variables, such as pathologic stage, age at diagnosis, and recurrence, in a case series of African-American men.


METHODS
Peripheral blood DNA samples from 114 African-American men with prostate cancer, including 106 who had undergone radical prostatectomy, were genotyped for six single-nucleotide polymorphisms on three 8q24 regions. The presence of these single-nucleotide polymorphisms was compared with clinicopathologic and follow-up data after radical prostatectomy.


RESULTS
The mean age of diagnosis and follow-up time were 57.4 (+/-8.9) years and 49.1 (+/-31.6) months, respectively. Patients carrying the Broad11934905 A risk allele, which is specific for African ancestry, were more likely to have a higher pathologic stage (pT(3-4)) than individuals with the wild type (odds ratio, 4.48; 95% confidence interval, 1.42-14.14; P = 0.011). A trend toward increased frequency of and shorter time to biochemical recurrence was noted in patients with this risk allele on Kaplan-Meier unadjusted survival analysis (P = 0.076).


CONCLUSIONS
The Broad11934905 polymorphism at 8q24, which is only found in people of African ancestry, is associated with an increase in non-organ-confined prostate cancer at prostatectomy. In addition, for those with this risk allele, there is a trend toward early biochemical recurrence that requires validation in larger studies.
Whitman
Eric J
EJ
Urology Service, Department of Surgery, Walter Reed Army Medical Center, Washington, District of Columbia, USA.
Pomerantz
Mark
M
Chen
Yongmei
Y
Chamberlin
Michael M
MM
Furusato
Bungo
B
Gao
Chunling
C
Ali
Amina
A
Ravindranath
Lakshmi
L
Dobi
Albert
A
Sesterhenn
Isabell A
IA
Sestrehenn
Isabell A
IA
McLeod
David G
DG
Srivastava
Shiv
S
Freedman
Matthew
M
Petrovics
Gyorgy
G
D001741:Black or African American / Q000235:genetics*; D000483:Alleles; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D012307:Risk Factors