Association of reported prostate cancer risk alleles with PSA levels among men without a diagnosis of prostate cancer.
BACKGROUND
Prostate specific antigen (PSA) is widely used for prostate cancer screening but its levels are influenced by many non cancer-related factors. The goal of the study is to estimate the effect of genetic variants on PSA levels.


METHODS
We evaluated the association of SNPs that were reported to be associated with prostate cancer risk in recent genome-wide association studies with plasma PSA levels in a Swedish study population, including 1,722 control subjects without a diagnosis of prostate cancer.


RESULTS
Of the 16 SNPs analyzed in control subjects, significant associations with PSA levels (P < or = 0.05) were found for six SNPs. These six SNPs had a cumulative effect on PSA levels; the mean PSA levels in men were almost twofold increased across increasing quintile of number of PSA associated alleles, P-trend = 3.4 x 10(-14). In this Swedish study population risk allele frequencies were similar among T1c case patients (cancer detected by elevated PSA levels alone) as compared to T2 and above prostate cancer case patients.


CONCLUSIONS
Results from this study may have two important clinical implications. The cumulative effect of six SNPs on PSA levels suggests genetic-specific PSA cutoff values may be used to improve the discriminatory performance of this test for prostate cancer; and the dual associations of these SNPs with PSA levels and prostate cancer risk raise a concern that some of reported prostate cancer risk-associated SNPs may be confounded by the prevalent use of PSA screening.
Wiklund
Fredrik
F
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Zheng
S Lilly
SL
Sun
Jielin
J
Adami
Hans-Olov
HO
Lilja
Hans
H
Hsu
Fang-Chi
FC
Stattin
Pär
P
Adolfsson
Jan
J
Cramer
Scott D
SD
Duggan
David
D
Carpten
John D
JD
Chang
Bao-Li
BL
Isaacs
William B
WB
Grönberg
Henrik
H
Xu
Jianfeng
J
D016022:Case-Control Studies; D005787:Gene Frequency / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017430:Prostate-Specific Antigen / Q000097:blood / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D012042:Registries; D012307:Risk Factors; D013548:Sweden
D017430:Prostate-Specific Antigen