Gene-based Score to Predict the Age of Onset of Aggressive Prostate Cancer

Highlights:

• Prostate-specific antigen (PSA) test used for the screening of prostate cancer often results in false positive results.
• As a result, people are often over diagnosed and over treated for prostate cancer, which is usually non-aggressive.
• A genetic score can possibly identify the age men are likely to develop prostate cancer and the individuals that require PSA testing.

Scientists have developed a score which could predict the age of onset of aggressive prostate cancer and can guide when men should undergo the PSA (prostate-specific antigen) screening test. The details were published in BMJ. The scientists used genome-wide association studies (GWAS) to assess if genetic information can predict the risk of developing aggressive prostate cancer. They examined small variations of the genes called single-nucleotide polymorphisms (SNPs) from the genetic information obtained from 31,747 European men, whose age, prostate cancer status and genetic status was known. Based on their examination of more than two hundred thousand SNPs and epidemiological surveys, they developed the polygenic hazard score, and in addition, validated the score.

The scientists found that:

• The score, calculated from 54 single nucleotide polymorphisms, significantly predicted the age of the diagnosis of aggressive prostate cancer. The hazard ratio for aggressive prostate cancer was 2.9 times in men with high scores (in the top 2% of the score) as compared to men with average scores.
• The number of men who tested positive for PSA was higher for those with a high score.
• Around 25% men with a high score and a positive PSA test signaled the diagnosis of aggressive prostate cancer.
• People with low scores but high PSA levels had a lower risk.
• Though a family history of prostate cancer is related to prostate cancer risk, however, it did not predict the age of onset of the cancer, and did not improve prediction over the hazard score alone.

The hazard score will be particularly useful in deciding which men are likely to benefit the most from PSA testing in terms of detecting prostate cancer early and detection of aggressive cancer. Since the genetic information in an individual does not change, the score can be estimated at any time, and can be used to determine whether a person should undergo screening and when to undergo it. This could avoid unnecessary testing in men at low risk.

Further testing of the score will be needed before it can be widely used. In addition, it will have to be validated in people of other ethnicities as well.

About Prostate Cancer

Prostate cancer is a common cancer in men and is second only to lung cancer. Most men develop a non-aggressive form of the cancer that does not kill the patient. More aggressive forms are less frequent but often affect younger males. Prostate cancer usually does not cause symptoms early in the disease. A rectal examination during routine checkups can help to diagnose prostate cancer early.

A blood test that measures the PSA levels has been used in the screening of the cancer. Although high levels could indicate the presence of a prostate cancer and require further testing, the PSA can sometimes increase in non-cancerous conditions like prostatic inflammation, and may result in false-positive results and requiring the patient to undergo unnecessary further testing, and sometimes aggressive treatments, which may actually not be needed.

Reference:

1. Seibert TM et al. Polygenic hazard score to guide screening for aggressive prostate cancer: development and validation in large scale cohorts BMJ 2018;360:j5757. Doi: https://doi.org/10.1136/bmj.j5757

Source-Medindia