Genetic Tests

New Guidelines Advise Against Using Polygenetic Risk Scores for Routine Patient Management

New guidelines from the National Comprehensive Cancer Network (NCCN) advise against using polygenetic risk scores for routine patient management and update previous recommendations for assessing hereditary cancer risk of the breast, ovaries, and pancreas as well as the use of cascade testing.

Polygenic Risk Scores

Polygenic risk scores reflect a mathematical aggregate of risk conferred by many DNA variants to estimate the likelihood of a specific outcome, such as disease onset in an individual. The scores are the output of statistical models developed using data from large genome-wide association studies (GWAS).

Such scores “should not be used for clinical management at this time,” advises the NCCN in the latest version of its clinical practice guidelines, entitled “Genetic/Familial Hight-Risk Assessment: Breast, Ovarian, and Pancreatic” published on Sept. 8. “There are significant limitations in the interpretation of polygenic risk scores,” according to the guidelines, which suggests instead using such scores for clinical trials.

Genetic Assessments Associated with Prostate Cancer Risks

The NCCN also provides update guidance on when language on when personal and family history of prostate cancer indicates the need for genetic testing for high-penetrance breast and ovarian cancer risk genes, such as BRCA1, BRCA2, CDH1, PALB2, PTEN, and TP53. According to the guidelines:

  • Any patients diagnosed with prostate cancer regardless of age should be tested if they have metastatic, intraductal/cribriform histology, or are in a high- or very high-risk group;
  • Any patients diagnosed with prostate cancer regardless of age or risk group, should be tested if they have: (i) Ashkenazi Jewish ancestry; (ii) at least one close relative with breast cancer diagnosed at age 50 or younger; (iii) at least one close relative with ovarian, pancreatic or metastatic or intraductal/cribriform prostate cancer regardless of age; or
  • At least two close relatives with breast or prostate cancer regardless of grade or age of diagnosis.

Cascade Testing

Cascade testing is a systematic process for the identification of individuals at risk for a hereditary condition which uses genetic testing to identify a pathogenic variant associated with the condition in the individual and thence to his/her at-risk biologic relatives. The process is repeated as more affected individuals or pathogenic variant carriers are identified.

The new guidelines revise NCCN’s criteria for cascade testing who have a family history but no personal history of cancer. If the unaffected individual’s affected relative has pancreatic cancer or metastatic, intraductal/cribriform, or high-/very high-risk prostate cancer, only first-degree relatives of the affected individual should be offered cascade testing, the NCCN. More distant relatives may be offered testing if there is additional history of cancers in the family indicating the need.


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