Prostate cancer susceptibility variants confer increased risk of disease progression.
BACKGROUND
Genome-wide association studies have identified numerous single nucleotide polymorphisms (SNP) associated with the risk of prostate cancer. Our objective was to determine whether these SNPs affect the progression of prostate cancer.


METHODS
We genotyped 26 SNPs previously associated with prostate cancer risk among 788 aggressive prostate cancer patients who were treated by radical prostatectomy or radiation therapy. Prostate cancer progression was defined as biochemical recurrence based on posttreatment prostate-specific antigen levels of >0.3 ng/mL for radical prostatectomy patients or a 2-ng/mL increase above the nadir for radiation therapy patients, initiation of hormone treatment, or metastases. We assessed the association between independent and combined SNPs and disease progression by Cox proportional hazards regression.


RESULTS
Five SNPs showed independent associations with prostate cancer progression (rs12621278, rs629242, rs9364554, rs4430796, and rs5945572) based on stepwise regression analysis. The strongest SNP was rs12621278 in the ITGA6 locus, which was associated with a 2.4-fold increased risk of progression (P = 0.0003). When considering the sum of risk alleles across these five SNPs, each additional allele was associated with a 29% increase in risk of progression (95% confidence interval, 1.12-1-47).


CONCLUSIONS
We found that five of the recently highlighted prostate cancer susceptibility loci also influence prostate cancer progression beyond the known clinicopathologic predictors. If confirmed, these genetic variants might help clarify which tumors are likely to progress and require more aggressive treatment in contrast to those that might not have substantial effects on morbidity or mortality.


CONCLUSIONS
Genetic susceptibility variants for prostate cancer development may also inform disease progression.
Cheng
Iona
I
Epidemiology Program, Cancer Research Center of Hawai'i, University of Hawai'i, Honolulu, Hawaii, USA.
Plummer
Sarah J
SJ
Neslund-Dudas
Christine
C
Klein
Eric A
EA
Casey
Graham
G
Rybicki
Benjamin A
BA
Witte
John S
JS
D000368:Aged; D016022:Case-Control Studies; D018450:Disease Progression; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000235:genetics* / Q000473:pathology / Q000601:surgery
D017430:Prostate-Specific Antigen