Evaluation of 8q24 and 17q risk loci and prostate cancer mortality.
OBJECTIVE
Variants at chromosomal loci 8q24 and 17q are established risk factors for prostate cancer. Many studies have confirmed the findings for risk, but few have examined aggressiveness and other clinical variables in detail. Additionally, Gleason score is typically used as a surrogate for the primary end point of prostate cancer mortality. We investigated whether the 8q24 and 17q risk variants are associated with clinical variables as well as prostate cancer mortality.


METHODS
In the Physicians' Health Study (1,347 cases and 1,462 controls), the Dana-Farber Harvard Cancer Center Specialized Program of Research Excellence (Gelb Center; 3,714 cases), and the Fred Hutchinson Cancer Research Center King County Case-Control Studies (1,308 cases and 1,266 controls), we examined eight previously identified 8q24 and 17q risk variants for association with prostate cancer mortality in men of European ancestry. We considered associations with other surrogate markers of prostate cancer aggressiveness, such as Gleason score, pathologic stage, prostate-specific antigen at diagnosis, and age at diagnosis.


RESULTS
Six of the eight variants were confirmed as prostate cancer risk factors. Several variants were nominally associated with age at diagnosis; when totaling all alleles for single nucleotide polymorphisms significantly associated with risk, each additional allele decreased age at diagnosis by an average of 6 months in the Physicians' Health Study (P = 0.0005) and 4 months in the Dana-Farber Harvard Cancer Center Specialized Program of Research Excellence (Gelb Center) cohort (P = 0.0016). However, there were no statistically significant associations with prostate cancer mortality.


CONCLUSIONS
Our results suggest that the 8q24 and 17q prostate cancer risk variants may influence age at diagnosis but not disease aggressiveness.
Penney
Kathryn L
KL
Department of Epidemiology, Harvard School of Public Health, Harvard University, Cambridge, Massachusetts, USA.
Salinas
Claudia A
CA
Pomerantz
Mark
M
Schumacher
Fredrick R
FR
Beckwith
Christine A
CA
Lee
Gwo-Shu
GS
Oh
William K
WK
Sartor
Oliver
O
Ostrander
Elaine A
EA
Kurth
Tobias
T
Ma
Jing
J
Mucci
Lorelei
L
Stanford
Janet L
JL
Kantoff
Philip W
PW
Hunter
David J
DJ
Stampfer
Meir J
MJ
Freedman
Matthew L
ML
D000368:Aged; D016022:Case-Control Studies; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D015331:Cohort Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000401:mortality*; D012307:Risk Factors; D015996:Survival Rate