Model development

PREMM stands for PREdiction Model for gene Mutations. The PREMM prediction model is rigorously tested, widely recognized, and recommended by several professional societies, including the National Comprehensive Cancer Network, the American College of Gastroenterology, and the U.S. Multi-Society Task Force on Colorectal Cancer.

PREMM5 model

The PREMM5 model was introduced in 2017 (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) and estimates the overall cumulative probability of having an MLH1, MSH2, MSH6, PMS2, and EPCAM gene mutation. This model replaces the PREMM1,2,6 model. It includes age at genetic testing as a predictor variable and factors in updated upper and lower age limits related to cancer diagnosis in the patient and first- and second-degree relatives to adjust for any extreme ages of cancer diagnoses.

PREMM1,2,6 model

The PREMM1,2,6 model was introduced in 2011 (Gastroenterology 2011;140:73-81; Erratum in: Gastroenterology 2012; 143:1399) and estimated the overall cumulative probability of having an MLH1, MSH2, and MSH6 gene mutation. The model also provided individual, gene-specific risk estimates for each of the three mismatch repair genes and replaced the original PREMM model called PREMM1,2. The PREMM1,2,6 model and web-based calculator was modified in March 2013 by adjusting the upper and lower age limits related to cancer diagnoses in the patient and first- and second-degree relatives. The age variable required truncation to adjust for any extreme ages of cancer diagnoses. The equation and regression coefficients otherwise remained the same.

PREMM1,2 model

The PREMM1,2 model was introduced in 2006 and stands for Prediction Model for MLH1 and MSH2 gene mutations. PREMM1,2 provided the overall cumulative probability of having an MLH1 and MSH2 gene mutation. This version of the calculator has been archived for historical purposes.

References

Kastrinos F, Uno H, Ukaegbu C, Alvero C, McFarland A, Yurgelun MB, Kulke MH, Schrag D, Meyerhardt JA, Fuchs CS, Mayer RJ, Ng K, Steyerberg EW, Syngal S.
Development and validation of the PREMM5 model for comprehensive risk assessment of Lynch syndrome.
Journal of Clinical Oncology. 2017 May; Advance online publication.

Kastrinos F, Ojha RP, Leenen C, Alvero C, Mercado RC, Balmana J, Valenzuela I, Balaguer F, Green R, Lindor NM, Thibodeau SN, Newcomb P, Win AK, Jenkins M, Buchanan DD, Bertario L, Sala P, Hampel H, Syngal S, Steyerberg EW, for the Lynch Syndrome prediction model validation study group.
Comparison of Prediction Models for Lynch Syndrome Among Individuals With Colorectal Cancer.
Journal of the National Cancer Institute. 2016 Feb 1;108(2):djv308.

Kastrinos F, Steyerberg EW, Balmaña J, Mercado R, Gallinger S, Haile R, Casey G, Hopper JL, LeMarchand L, Lindor NM, Newcomb PA, Thibodeau SN, Syngal S, Colon Cancer Family Registry.
Comparison of the clinical prediction model PREMM1,2,6 and molecular testing for the systematic identification of Lynch syndrome in colorectal cancer.
Gut. 2013 Feb;62(2):272-9.

Kastrinos F, Steyerberg EW, Mercado R, Balmaña J, Holter S, Gallinger S, Siegmund KD, Church JM, Jenkins MA, Lindor NM, Thibodeau SN, Burbidge LA, Wenstrup RJ, Syngal S.
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.

Balaguer F, Balmaña J, Castellví-Bel S, Steyerberg EW, Andreu M, Llor X, Jover R, Syngal S, Castells A, Gastrointestinal Oncology Group of the Spanish Gastroenterological Association.
Validation and extension of the PREMM1,2 model in a population-based cohort of colorectal cancer patients.
Gastroenterology. 2008 Jan;134(1):39-46.

Balmaña J, Stockwell DH, Steyerberg EW, Stoffel EM, Deffenbaugh AM, Reid JE, Ward B, Scholl T, Hendrickson B, Tazelaar J, Burbidge LA, Syngal S.
Prediction of MLH1 and MSH2 mutations in Lynch syndrome.
JAMA. 2006 Sep 27;296(12):1469-78.

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