Community Practice Implementation of a Self-administered Version of PREMM1,2,6 to Assess Risk for Lynch Syndrome

Abstract

Background & aims: Lynch syndrome is a genetic disorder that greatly increases risk for colorectal and other cancers, although it is underdiagnosed. Prediction of MLH1, MSH2, and MSH6 (PREMM_1,2,6) is a web-based tool that analyzes individuals' personal/family histories of cancer to quantify their likelihood of carrying a germline mutation associated with Lynch syndrome. We investigated the feasibility of systematic risk assessment for Lynch syndrome in a community gastroenterology practice using a patient-completed version of PREMM_1,2,6.

Methods: PREMM_1,2,6 was adapted into a computer tablet version designed for self-administration by patients. Individuals presenting to a community gastroenterology office and endoscopy facility in California completed the PREMM_1,2,6 assessment before their visit (n = 3134). The total study duration (8 months) comprised a 2-month initiation period (May 1-June 30, 2013) and a 6-month study period (July 1-December 31, 2013). Genetic counseling and germline analysis for mutations in genes associated with Lynch syndrome (MLH1, MSH2, MSH6, PMS2, and EPCAM) were offered to individuals with PREMM_1,2,6 scores of 5% or higher. Patients and providers completed surveys to evaluate the feasibility and satisfaction with the process.

Results: Of the 3134 individuals assessed by PREMM_1,2,6 during the 6-month study period, 177 individuals (5.6%) had scores of 5% or higher. Of these, 146 individuals underwent genetic testing, along with 28 additional participants recruited nonconsecutively during the initiation period. Mutations associated with Lynch syndrome were detected in 3 of the 146 individuals (2.1%) with PREMM_1,2,6 scores of 5% or higher who underwent germline testing, and 3 of the 28 patients (10.7%) recruited during study initiation with PREMM_1,2,6 scores of 5% or higher. Of the participants who underwent genetic analysis, 98.6% stated that they understood the information provided to them. All of the surveyed providers stated that they were satisfied with the incorporation of PREMM_1,2,6 into their clinical practice, and that they would continue using it to assess risk for Lynch syndrome.

Conclusions: A patient self-administered version of the PREMM_1,2,6 Lynch syndrome risk assessment model can be used systematically in community-based gastroenterology and endoscopy practices.

Keywords: Endometrial Cancer; Familial Colon Cancer; Genetics; Protocol Integration.

Figure 1

PREMM_1,2,6 Patient Administered Questionnaire^{* *}Because the PREMM_1,2,6 questionnaire was adapted for use on a tablet device in this study, its appearance on the user interface was slightly different as skip logic, where one question appears at a time, was employed.

Figure 2

PREMM_1,2,6 Patient Questionnaire Results^{* *}Sample output from the patient questionnaire generated by a hypothetical patient