Association of prostate cancer risk variants with clinicopathologic characteristics of the disease.
OBJECTIVE
Fifteen independent genetic variants have been implicated in prostate cancer risk by recent genome-wide association studies. However, their association with clinicopathologic features of prostate cancer is uncertain.


METHODS
We systematically evaluated these 15 variants in 1,563 prostate cancer patients undergoing radical prostatectomy, taking advantage of the uniform tumor stage and grade information available for each of these cases. Associations of these variants with aggressiveness, pathologic Gleason scores, pathologic stage, age at diagnosis, or serum prostate-specific antigen (PSA) levels were tested.


RESULTS
After adjusting for multiple testing, none of the single nucleotide polymorphisms was individually or cumulatively associated with aggressiveness or individual clinicopathologic variables of prostate cancer such as Gleason scores, pathologic stage, or age at diagnosis of prostate cancer. The reported risk allele (G) for single nucleotide polymorphism rs2735839 in the KLK3 gene at 19q13 was more frequent in less aggressive prostate cancer patients (0.89) than in more aggressive prostate cancer patients (0.86; nominal P = 0.03) or in controls (0.86; nominal P = 0.04). Considering that this allele was also significantly associated with higher serum PSA levels among controls (nominal P = 0.003), the observed trend of higher frequency of this risk allele between less and more aggressive prostate cancer, or between less aggressive and controls may be due to detection bias of PSA screening.


CONCLUSIONS
Prostate cancer risk variants recently discovered from genome-wide case-control association studies are not associated with clinicopathologic variables in this population. Case-case studies are urgently needed to discover genetic variants that predict tumor aggressiveness.
Xu
Jianfeng
J
Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Isaacs
Sarah D
SD
Sun
Jielin
J
Li
Ge
G
Wiley
Kathleen E
KE
Zhu
Yi
Y
Hsu
Fang-Chi
FC
Wiklund
Fredrik
F
Turner
Aubrey R
AR
Adams
Tamara S
TS
Liu
Wennuan
W
Trock
Bruce J
BJ
Partin
Alan W
AW
Chang
Baoli
B
Walsh
Patrick C
PC
Grönberg
Henrik
H
Isaacs
William
W
Zheng
Siqun
S
D000368:Aged; D014408:Biomarkers, Tumor; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D012307:Risk Factors
D014408:Biomarkers, Tumor; D017430:Prostate-Specific Antigen
Cancer Epidemiol Biomarkers Prev. 2007 Mar;16(3):610-2
17372260
Nat Genet. 2007 May;39(5):638-44
17401364
Cancer Res. 2007 Apr 1;67(7):2951-6
17409400
Genome Res. 2007 Dec;17(12):1717-22
17978284
Hum Mol Genet. 2004 Apr 1;13 Spec No 1:R103-21
14749351
Nat Genet. 2007 Aug;39(8):977-83
17603485
Nat Genet. 2008 Mar;40(3):281-3
18264098
Prostate. 2008 May 15;68(7):691-7
18361410
Urol Clin North Am. 2001 Aug;28(3):567-94
11590815
Cancer Epidemiol Biomarkers Prev. 2007 Apr;16(4):809-14
17416775
Proc Natl Acad Sci U S A. 2006 Sep 19;103(38):14068-73
16945910
Am J Surg Pathol. 2005 Sep;29(9):1228-42
16096414
Nat Genet. 2006 Jun;38(6):652-8
16682969
Cancer Res. 2007 Apr 1;67(7):2944-50
17409399
Nat Genet. 2007 May;39(5):631-7
17401366
Nat Genet. 2008 Mar;40(3):310-5
18264096
J Natl Cancer Inst. 2007 Dec 19;99(24):1836-44
18073375
J Natl Cancer Inst. 2007 Oct 17;99(20):1525-33
17925536
N Engl J Med. 2008 Feb 28;358(9):910-9
18199855
Nat Genet. 2007 May;39(5):645-9
17401363
Eur J Hum Genet. 2008 Apr;16(4):496-505
18231127
Nat Genet. 2008 Mar;40(3):316-21
18264097
Microsc Res Tech. 2000 Dec 1;51(5):423-9
11074612
Nat Genet. 2007 Jul;39(7):906-13
17572673
Urology. 2008 Jul;72(1):172-6
18304619