Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer)

PREMM1,2,6 Model: Prediction Model for MLH1, MSH2, and MSH6 Gene Mutations

The PREMM1,2,6 model is a clinical prediction algorithm designed for use by healthcare professionals to estimate the cumulative and individual probabilities that an individual is an MLH1, MSH2, or MSH6 mutation carrier. Mutations in these genes are found in most patients with Lynch syndrome.

Proband Information

("Proband" refers to the individual being evaluated. Ideally, this individual should have a cancer diagnosis.)

Is the proband male?

Yes

How many separate colorectal
cancers has the proband had?

None

One

Two or more

If one, what was the age at diagnosis?
(if unknown, estimate)

If two or more, what was the youngest age at diagnosis?
(if unknown, estimate)

Has the proband had endometrial cancer?

Yes

What was the youngest age at diagnosis?
(if unknown, estimate)

Has the proband had another
HNPCC-associated cancer?

Yes

(Other HNPCC-associated cancers include ovary, stomach, small intestine, urinary tract/kidney, bile ducts, glioblastoma multiforme, sebaceousgland tumors, and pancreas.)

Relatives Information - First Degree

(Only from affected side of family)

How many first-degree relatives
have had colorectal cancer?

None

One

Two or more

If one, what was his/her age at diagnosis?
(if unknown, estimate)

If two or more, what was the youngest age at diagnosis?
(if unknown, estimate)

How many first-degree relatives
have had endometrial cancer?

None

One

Two or more

If one, what was her age at diagnosis?
(if unknown, estimate)

If two or more, what was the youngest age at diagnosis?
(if unknown, estimate)

Have any first-degree relatives
had another HNPCC-associated cancer?

Yes

Relatives Information - Second Degree

(Only from affected side of family)

How many second-degree relatives
have had colorectal cancer?

None

One

Two or more

If one, what was his/her age at diagnosis?
(if unknown, estimate)

If two or more, what was the youngest age at diagnosis?
(if unknown, estimate)

How many second-degree relatives
have had endometrial cancer?

None

One

Two or more

If one, what was her age at diagnosis?
(if unknown, estimate)

If two or more, what was the youngest age at diagnosis?
(if unknown, estimate)

Have any second-degree relatives
had another HNPCC-associated cancer?

Yes

Predicted Probability of MLH1, MSH2, or MSH6 Mutation

Predicted Probability of MLH1 Mutation

Predicted Probability of MSH2 Mutation

Predicted Probability of MSH6 Mutation

If the predicted probability of any mutation is more than five percent, please consider a genetic evaluation for your patient. You may refer your patient to our Cancer Risk and Prevention Clinic, by calling (617) 632-2178 to schedule a clinic appointment. If you are not in the Boston area, please contact a cancer center nearest you, and they may be able to refer you to a genetics program in your area.

Additional Information

An earlier version of this calculator (PREMM1,2) estimated the cumulative probability of having an MLH1 or MSH2 mutation whereas the updated version on this page (PREMM1,2,6) provides estimates for the cumulative and individual probabilities of MLH1, MSH2, or MSH6 mutations[1]. We recommend using the updated calculator, but the earlier version is archived for historical purposes (e.g. for investigators who used the earlier version for research studies). For any questions, please contact us at ssyngal@partners.org.

View the earlier version of the calculator

Reference

Kastrinos F, Steyerberg EW, Mercado R, Balma�a J, Holter S, Gallinger S, Siegmund KD, Church JM, Jenkins MA, Lindor NM, Thibodeau SN, Burbidge LA, Wenstrup RJ, Syngal S. The PREMM 1,2,6 Model Predicts Risk of MLH1, MSH2, and MSH6 Germline Mutations Based on Cancer History. Gastroenterology. 2010 Aug 18. [Epub ahead of print]