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26 Feb 2018 - 01 Mar 2018
05 Mar 2018 - 06 Mar 2018

Polygenic Score Predicts Prostate Cancer Development

By Labmedica International staff writers
Posted on 31 Jan 2018
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Image: Cell division of a prostate-cancer cell, captured in a colored scanning electron micrograph (SEM) (Photo courtesy of Getty Images).
Image: Cell division of a prostate-cancer cell, captured in a colored scanning electron micrograph (SEM) (Photo courtesy of Getty Images).
Currently, detection of prostate cancer relies primarily upon the prostate-specific antigen (PSA) screening blood test, but PSA testing is not very good as a screening tool. While it reduces deaths from prostate cancer, indiscriminate PSA screening also produces false positive results and encourages over-detection of non-aggressive, slow-growing tumors.

Because of concerns over a high rate of false positive results, in addition to aggressive treatment of apparently indolent disease, however, many clinical guidelines do not endorse universal screening and instead stress the importance of taking into account individual patient risk factors to decide whether to screen.

An international multidisciplinary team of scientists led by those at University of California, San Diego (La Jolla, CA, USA) used genome-wide association studies (GWAS) to determine whether a man's genetic predisposition to developing prostate cancer could be used to predict his risk of developing the aggressive and lethal form of the disease. GWAS search individual genomes for small variations, called single-nucleotide polymorphisms (SNPs) that occur more frequently in people with a particular disease than in people without the disease. The development dataset comprised 31,747 men; the validation dataset comprised 6,411 men.

The team found that in the independent validation set, the hazard score calculated from 54 single nucleotide polymorphisms was a highly significant predictor of age at diagnosis of aggressive cancer. When men in the validation set with high scores were compared with those with average scores, the hazard ratio for aggressive cancer was 2.9 (95% confidence interval 2.4 to 3.4). Inclusion of family history in a combined model did not improve prediction of onset of aggressive prostate cancer and polygenic hazard score performance remained high when family history was accounted for. Additionally, the positive predictive value of PSA screening for aggressive prostate cancer was increased with increasing polygenic hazard score.

Anders M. Dale, PhD, a professor and a chief investigator of the study said, “This kind of genetic risk stratification is a step toward individualized medicine. PSA tests are much more predictive of aggressive prostate cancer in men with high polygenic hazard score than in those with low polygenic hazard score. This suggests that polygenic hazard score can help physicians determine whether to order a PSA test for a given patient, in the context of the patient's general health and other risk factors.” The study was published on January 10, 2018, in the journal BMJ.

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University of California, San Diego


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