Association of reported prostate cancer risk alleles with PSA levels among men without a diagnosis of prostate cancer

• Published in: The Prostate Vol. 69; no. 4; pp. 419 - 427
• Main Authors: Wiklund, Fredrik, Zheng, S. Lilly, Sun, Jielin, Adami, Hans-Olov, Lilja, Hans, Hsu, Fang-Chi, Stattin, Pär, Adolfsson, Jan, Cramer, Scott D., Duggan, David, Carpten, John D., Chang, Bao-Li, Isaacs, William B., Grönberg, Henrik, Xu, Jianfeng
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.03.2009; Wiley-Liss
• Subjects: bias; Biological and medical sciences; Case-Control Studies; Clinical Medicine; Gene Frequency - genetics; genetic; Genetic Predisposition to Disease - genetics; Gynecology. Andrology. Obstetrics; Humans; Klinisk medicin; KLK3; Male; Male genital diseases; Medical and Health Sciences; Medical sciences; Medicin och hälsovetenskap; Multivariate Analysis; Nephrology. Urinary tract diseases; Obstetrics, Gynecology and Reproductive Medicine; Polymorphism, Single Nucleotide - genetics; Prostate-Specific Antigen - blood; Prostate-Specific Antigen - genetics; Prostatic Neoplasms - blood; Prostatic Neoplasms - diagnosis; Prostatic Neoplasms - genetics; Registries; Reproduktionsmedicin och gynekologi; Risk Factors; Sweden; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Sweden; Human; genetic; Andrology; Nephrology; Urinary system disease; Prostate disease; Report; Bias; Gynecology; Male; Tumoral marker; KLK3; Malignant tumor; Prostate specific antigen; Allele; Association; Risk factor; Adult; Genetics; Diagnosis; Male genital diseases; Prostate cancer; Cancer
• ISSN: 0270-4137; 1097-0045; 1097-0045
• DOI: 10.1002/pros.20908

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 ≤ 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 × 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. Prostate 69:419–427, 2009. © 2008 Wiley‐Liss, Inc.