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:
- A personal or family history of colorectal cancer, endometrial (uterine) cancer, or other Lynch syndrome-associated cancers
- 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)
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 May 10. Advance online publication. DOI: 10.1200/JCO.2016.69.6120. PREMM5 JCO)