Research ArticleHuman Genetics

Genetic Correction of PSA Values Using Sequence Variants Associated with PSA Levels

Science Translational Medicine  15 Dec 2010:
Vol. 2, Issue 62, pp. 62ra92
DOI: 10.1126/scitranslmed.3001513

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SNPping Away at Prostate Cancer

Measuring prostate-specific antigen (PSA) in serum is the only diagnostic test for prostate cancer and is used as a screening tool for deciding whether to perform a biopsy. Yet, this diagnostic test is far from ideal, with more than a third of men with serum PSA levels of 10 ng/ml or greater having no evidence of prostate cancer at biopsy, and some men with very low PSA levels (less than the lower threshold of 2.5 ng/ml), who are not given a biopsy but yet end up having prostate cancer. The lack of specificity and sensitivity of the PSA test and the many confounding factors that influence the test result, including medications, inflammation, and, of course, genotype, have reduced the value of this screening tool. As with most cancers, early detection of prostate cancer leads to a greatly improved chance of survival, so improving the predictive accuracy of this test is of paramount importance.

In an effort to investigate whether genome sequence variants can be used to make the PSA test more sensitive, Gudmundsson and colleagues have undertaken a genome-wide association study in 15,757 Icelandic men and 454 British men not yet diagnosed with prostate cancer to see whether they can tie sequence variants [single-nucleotide polymorphisms (SNPs)] to serum PSA levels. The authors identify six loci with SNPs that correlate with PSA levels. They then probed these data more deeply. They looked at these loci in 3834 men who underwent subsequent biopsy of the prostate and demonstrate that three of these loci (10q26, 12q24, and 19q13.33) are associated not only with higher PSA levels but also with a higher probability of a negative biopsy result. The authors suggest that this genotype information should be used to calculate a personalized “cutoff” value for serum PSA levels in each individual to improve the predictive accuracy of the test and to ensure that only men who need a prostate biopsy are subjected to this procedure.


  • * These authors contributed equally to this work.

  • Citation: J. Gudmundsson, S. Besenbacher, P. Sulem, D. F. Gudbjartsson, I. Olafsson, S. Arinbjarnarson, B. A. Agnarsson, K. R. Benediktsdottir, H. J. Isaksson, J. P. Kostic, S. A. Gudjonsson, S.N. Stacey, A.Gylfason, A. Sigurdsson, H. Holm, U. S. Bjornsdottir, G. I. Eyjolfsson, S. Navarrete, F. Fuertes, M. D. Garcia-Prats, E. Polo, I. A. Checherita, M. Jinga, P. Badea, K. K. Aben, J. A. Schalken, I. M. van Oort, F. C. Sweep, B. T. Helfand, M. Davis, J. L. Donovan, F. C. Hamdy, K. Kristjansson, J. R. Gulcher, G. Masson, A. Kong, W. J. Catalona, J. I. Mayordomo, G. Geirsson, G. V. Einarsson, R. B. Barkardottir, E. Jonsson, V. Jinga, D. Mates, L. A. Kiemeney, D. E. Neal, U. Thorsteinsdottir, T. Rafnar, K. Stefansson, Genetic Correction of PSA Values Using Sequence Variants Associated with PSA Levels. Sci. Transl. Med. 2, 62ra92 (2010).