Contribution of Genetic Variation rs266882 to Prostate-Specific Antigen Levels in Healthy Controls with Serum PSA Below
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Contribution of Genetic Variation rs266882 to ProstateSpecific Antigen Levels in Healthy Controls with Serum PSA Below 2.0 ng/ml Jaeman Song • Heeyoon Park • Gilho Lee
Received: 21 December 2011 / Accepted: 15 November 2012 / Published online: 13 January 2013 Ó Springer Science+Business Media New York 2013
Abstract We evaluated the impact of genetic variation in the prostate-specific antigen (PSA) gene (rs266882) on serum PSA levels in healthy men as well as risk factors for benign prostate hypertrophy (BPH) and prostate cancer. The study population comprised 91 men with PSA levels below 2.0 ng/ml as healthy controls, 78 men with PSA 2–10 ng/ml as a BPH group, and 128 prostate cancer patients, all in Korea. DNA was amplified by polymerase chain reaction and the product was sequenced. We found that PSA levels were associated with a G/A polymorphism only in healthy controls. The transition, however, was not associated with PSA levels of BPH and cancer patients, nor was it a risk factor. In conclusion, this genetic factor is important for determining serum PSA levels in the naive group, whereas the disruption of prostatic architecture in BPH or prostate cancer may be a major determining factor for PSA levels. Keywords Serum prostate-specific antigen RS266882 Prostate cancer Genotyping
Introduction The prostate is the major site of prostate-specific antigen (PSA) expression in men, and the serum PSA level has become the most widely used marker for prostate cancer screening (Stephan et al. 2011). Prostate cancer screening based on serum PSA has increased the proportion of early stage prostate cancer detection (Hekal J. Song Department of Urology, Yonsei University Wonju College of Medicine, Wonju, South Korea H. Park G. Lee (&) Department of Urology, Dankook University College of Medicine, 359 Manghyang-ro, Cheonan, South Korea e-mail: [email protected]
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2009), and it may have influenced the recent decrease in prostate cancer mortality rates in the United States (Jemal et al. 2010). As a diagnostic marker, however, PSA is problematic; its limitations include low specificity and low sensitivity (Pienta 2009). Some men with high PSA levels do not have the disease, leading to unnecessary biopsies. Furthermore, substantial controversy also exists over its benefits for patient survival in the older population (Chou et al. 2011). Early diagnosis of prostate cancer in the younger population is an independent prognostic factor for better survival (Stephan et al. 2011; Hekal 2009). Moreover, the use of lower PSA cutoff values may detect prostate cancer more frequently in early, curable stages (Hekal 2009; Smith et al. 2000). For those reasons, early diagnosis of prostate cancer in younger men with lower PSA cutoff values has been of greater value for prolonged survival after definitive treatments. While lower PSA cutoffs increase the detection rate of prostate cancer, this approach decreases the specificity of the test (Stephan et al. 2011). Improving the accuracy of PSA
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