Lynch syndrome prediction model

MLH1, MSH2, MSH6, PMS2, and EPCAM gene mutations

The PREMM5 model is a clinical prediction algorithm that estimates the cumulative probability of an individual carrying a germline mutation in the MLH1, MSH2, MSH6, PMS2, or EPCAM genes. Mutations in these genes cause Lynch syndrome, an inherited cancer predisposition syndrome.

In addition to information about the individual being evaluated, the model requires:

  • Types of cancer and ages at diagnosis of first-degree relatives from the affected side of the family (parents, siblings, children)
  • Types of cancer and ages at diagnosis of second-degree relatives from the affected side of the family (grandparents, grandchildren, aunts, uncles, nieces, nephews)
1Patient information
2Relatives: First-degree
First-degree relatives include parents, siblings, children, only from affected side of family
3Relatives: Second-degree
Second-degree relatives are grandparents, grandchildren, aunts, uncles, nieces, nephews, only from affected side of family

Overall predicted probability of MLH1, MSH2, MSH6, PMS2, or EPCAM mutation

If the overall predicted probability is ≥ 2.5%

  • Referral for genetic evaluation is recommended. This may include tumor sample microsatellite instability (MSI) or immunohistochemistry (IHC) testing, genetic counseling, and/or germline genetic testing. (Kastrinos F. et al. Development and validation of the PREMM5 model for comprehensive risk assessment of Lynch syndrome. Journal of Clinical Oncology. 2017. Advance online publication. PREMM5 JCO)