What is the Prediction Model for Gene Mutations (PREMM)?

The Prediction Model for Gene Mutations (PREMM) is a model for predicting the chance of having a Lynch syndrome mutation. It was first introduced in 2011 and quickly became part of professional society guidelines. The most recent version of this risk model, called PREMM5, was introduced in 2017 and modified to include additional genes now recognized to cause Lynch syndrome. The PREMM5 algorithm is made available online and free to use by the Dana-Farber Cancer Institute at http://premm.dfci.harvard.edu/.

What is Lynch Syndrome?

Lynch syndrome, also called Hereditary Non-polyposis Colon Cancer (HNPCC), is common and impacts at least one million individuals in the United States. It is caused by mutations in the MLH1, MSH2, MSH6, PMS2 or EPCAM genes. In addition to colon cancer, affected people are at higher risk for cancers involving the ovaries, endometrial lining, stomach, small intestine, brain, urinary tract, pancreas and the oil glands in skin. Lynch syndrome is inherited in a dominant manner, meaning that it can be seen in every generation of a family. Despite the signs that may be visible in one’s family health history, Lynch syndrome is often under-recognized. Early and pre-symptomatic diagnosis is important because it gives individuals the opportunity to pursue screening and intervention strategies proven to reduce the risk of developing Lynch syndrome-related cancers. The PREMM5 model is one evidence-based tool that has been developed to help clinicians recognize people who are at risk for Lynch syndrome.

How Premm5 Helps Identifies Lynch Syndrome

PREMM5 uses patient demographics, personal and family history of cancer, and the types of cancer with ages of diagnosis to determine the individual risk of having Lynch syndrome. Clinicians can enter this information online and receive an immediate probability risk assessment for the individual. This tool was validated in a cohort of 18,734 individuals who were tested for all five genes, MLH1, MSH2, MSH6, PMS2 and EPCAM, and supports genetic testing for individuals with a probability score of >2.5%. As a result, the National Comprehensive Cancer Network (NCCN) included the PREMM5 model in their most recent guidelines as one option to use to determine if a patient meets criteria for genetic testing for familial colorectal cancer.


  • Kastrinos F, Steyerberg EW, Mercado R, et al. The PREMM1,2,6 Model Predicts Risk of MLH1, MSH2, and MSH6 Germline Mutations Based on Cancer History. Gastroenterology. 2011 Jan;140(1):73-81. Erratum in: Gastroenterology. 2012 Nov;143(5):1399.
  • Kastrinos F, Uno H, Ukaegbu C, et al. Development and Validation of the PREMM5 Model for Comprehensive Risk Assessment of Lynch Syndrome. J Clin Oncol. 2017;35(19):2165-2172.
  • National Comprehensive Cancer Network. Guidelines for detection, prevention and risk reduction: Genetic/Familial High-Risk Assessment: Colorectal Guidelines (Version 2.2016). Available at: https://www.nccn.org/professionals/physician_gls/pdf/genetics_colon.pdf
  • Giardiello FM, Allen JI, Axilbund JE, Boland CR, Burke CA, Burt RW, Church JM, Dominitz JA, Johnson DA, Kaltenbach T, Levin TR. Guidelines on genetic evaluation and management of Lynch syndrome: a consensus statement by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology. 2014 Aug 31;147(2):502-26.