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Subspecialties Genetics and epigenetics, Oncology, Omics

PSA Accuracy Boost

Prostate-specific antigen (PSA) screening is a source of controversy – amid concerns surrounding possible overdiagnosis and unnecessary treatment, some organizations no longer recommend the assay, even as others argue that there is no alternative for early diagnosis of prostate cancer (PrCa) (1). Now, a genome-wide association study (GWAS) suggests that genetic testing could identify men at high risk of PrCa using blood or urine – and could increase the accuracy of PSA testing, too.

In a multicenter, international effort including the University of California, San Francisco (UCSF), US, PrCa risk factor status of 7,783 men with the disease were compared with that of 38,595 controls. Using 105 single nucleotide polymorphisms (SNPs) known to be associated with PrCa to produce an overall risk score, the selected SNPs were shown to explain 7.8 percent of disease heritability. However, the predictability was substantially higher using the entire GWAS array, which was able to account for around one-third (33.4 percent) of disease heritability (2). This strongly suggests that, as well as the known risks for the disease, there are many genetic factors still to be discovered.

The researchers also determined that men with risk scores in the top 10 percent of the group were six times more likely to be diagnosed with PrCa compared with those in the lowest 10 percent. This is comparable to the breast cancer risk of women who carry a BRCA1/2 mutation, points out study co-author, and UCSF professor of epidemiology and biostatistics, John Witte. But in contrast to BRCA, a validated test to determine PrCa mutation status has yet to be developed.

A genetic test could not only aid screening, says Witte, but also augment the value of the PSA test: “We are presently assessing the biological and functional relevance of the novel genetic variants we detected here. We are also now searching for variants that affect a man’s constitutive levels of PSA. With such information we could ‘normalize’ a man vs PSA levels to assess if they are inherently high or low PSA producers (i.e., regardless of PrCa status), and improve the ability of this test to more accurately screen for PrCa,” he says.

The significant differences in risk observed in the study are promising, especially in such a large dataset. If genetic analysis could be used to both increase PSA accuracy and to identify men at high risk of cancer, it could provide a valuable improvement to current screening techniques. The team now plan to correlate genetic variations to men who relapse despite treatment, with an aim of identifying men most likely to develop aggressive cancers.

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  1. The Pathologist, “The Great Prostate Debate”, 4, 16–25 (2015). Available at: Accessed October 5, 2015.
  2. TJ Hoffman, et al., “A large multiethnic genome-wide association study of prostate cancer identifies novel risk variants and substantial ethnic differences”, Cancer Discov, 5, 878–891 (2015). PMID: 26034056.
About the Author
Roisin McGuigan

I have an extensive academic background in the life sciences, having studied forensic biology and human medical genetics in my time at Strathclyde and Glasgow Universities. My research, data presentation and bioinformatics skills plus my ‘wet lab’ experience have been a superb grounding for my role as an Associate Editor at Texere Publishing. The job allows me to utilize my hard-learned academic skills and experience in my current position within an exciting and contemporary publishing company.

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