Familial Cancer

, Volume 8, Issue 4, pp 483–487

Are prediction models for Lynch syndrome valid for probands with endometrial cancer?

  • Floor J. Backes
  • Heather Hampel
  • Katherine A. Backes
  • Luis Vaccarello
  • George Lewandowski
  • Jeffrey A. Bell
  • Gary C. Reid
  • Larry J. Copeland
  • Jeffrey M. Fowler
  • David E. Cohn
Article

DOI: 10.1007/s10689-009-9273-5

Cite this article as:
Backes, F.J., Hampel, H., Backes, K.A. et al. Familial Cancer (2009) 8: 483. doi:10.1007/s10689-009-9273-5
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Abstract

Currently, three prediction models are used to predict a patient’s risk of having Lynch syndrome (LS). These models have been validated in probands with colorectal cancer (CRC), but not in probands presenting with endometrial cancer (EMC). Thus, the aim was to determine the performance of these prediction models in women with LS presenting with EMC. Probands with EMC and LS were identified. Personal and family history was entered into three prediction models, PREMM(1,2), MMRpro, and MMRpredict. Probabilities of mutations in the mismatch repair genes were recorded. Accurate prediction was defined as a model predicting at least a 5% chance of a proband carrying a mutation. From 562 patients prospectively enrolled in a clinical trial of patients with EMC, 13 (2.2%) were shown to have LS. Nine patients had a mutation in MSH6, three in MSH2, and one in MLH1. MMRpro predicted that 3 of 9 patients with an MSH6, 3 of 3 with an MSH2, and 1 of 1 patient with an MLH1 mutation could have LS. For MMRpredict, EMC coded as “proximal CRC” predicted 5 of 5, and as “distal CRC” three of five. PREMM(1,2) predicted that 4 of 4 with an MLH1 or MSH2 could have LS. Prediction of LS in probands presenting with EMC using current models for probands with CRC works reasonably well. Further studies are needed to develop models that include questions specific to patients with EMC with a greater age range, as well as placing increased emphasis on prediction of LS in probands with MSH6 mutations.

Keywords

Endometrial cancerHereditary nonpolyposis colon cancerLynch syndromeMismatch repair gene mutationsPrediction models

Abbreviations

HNPCC

Hereditary non-polyposis colorectal cancer

CRC

Colorectal cancer

MSI

Microsatellite instability

EMC

Endometrial cancer

MMR

Mismatch repair

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Floor J. Backes
    • 1
  • Heather Hampel
    • 2
  • Katherine A. Backes
    • 1
  • Luis Vaccarello
    • 3
  • George Lewandowski
    • 3
  • Jeffrey A. Bell
    • 4
  • Gary C. Reid
    • 4
  • Larry J. Copeland
    • 1
  • Jeffrey M. Fowler
    • 1
  • David E. Cohn
    • 1
  1. 1.The Division of Gynecologic Oncology, Department of Obstetrics and GynecologyThe Ohio State University College of MedicineColumbusUSA
  2. 2.Division of Human Genetics, Department of Internal MedicineThe Ohio State University College of MedicineColumbusUSA
  3. 3.Gynecologic Oncology and Pelvic Surgery AssociatesMount Carmel Health SystemColumbusUSA
  4. 4.Central Ohio Gynecologic OncologyRiverside Methodist HospitalColumbusUSA