Individual and cumulative association of prostate cancer susceptibility variants with clinicopathologic characteristics of the disease.
BACKGROUND
Recent genome-wide association studies have identified several independent single nucleotide polymorphisms (SNPs) strongly associated with prostate cancer (PCa) risk. However, their individual and cumulative associations with clinicopathologic characteristics of the disease remain inconclusive.


METHODS
We systematically evaluated 20 PCa risk SNPs in a cohort of 320 localized PCa patients receiving radical prostatectomy, and the associations of these variants with age at diagnosis, preoperative prostate-specific antigen concentration, Gleason score, pathologic stage, surgical margin, and lymph node metastasis were evaluated.


RESULTS
Eight SNPs, rs10486567 at 7p15, rs6465657 at 7q21, rs6983267, rs1447295, and rs4242382 at 8q24, 10993994 at 10q11, rs4430796 at 17q12, and rs266849 at 19q13, were significantly (P< or =0.048) associated with some specific clinicopathologic features. In combination of these 8 SNPs, men who carried 4 or 5, or more than 5 unfavorable alleles had an increasing likelihood of adverse clinicopathologic features, as compared with men who carried fewer than 4 unfavorable alleles (P for trend, 0.031, <0.001, 0.006, and 0.003, for Gleason scores 8-10, advanced pathologic stage, positive surgical margin, and lymph node metastasis, respectively).


CONCLUSIONS
Our results suggested that loci associated with PCa risk might also have a cumulative and significant association with disease aggressiveness.
Bao
Bo-Ying
BY
Department of Pharmacy, China Medical University, Taichung, Taiwan.
Pao
Jiunn-Bey
JB
Lin
Victor C
VC
Huang
Chun-Nung
CN
Chang
Ta-Yuan
TY
Lan
Yu-Hsuan
YH
Lu
Te-Ling
TL
Lee
Hong-Zin
HZ
Chen
Lu-Min
LM
Ting
Wen-Chien
WC
Hsieh
Chi-Jeng
CJ
Huang
Shu-Pin
SP
D000368:Aged; D000483:Alleles; D002874:Chromosome Mapping; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery