Implementing screening for Lynch syndrome among patients with newly diagnosed colorectal cancer: summary of a public health/clinical collaborative meeting

Abstract

Lynch syndrome is the most common cause of inherited colorectal cancer, accounting for approximately 3% of all colorectal cancer cases in the United States. In 2009, an evidence-based review process conducted by the independent Evaluation of Genomic Applications in Practice and Prevention Working Group resulted in a recommendation to offer genetic testing for Lynch syndrome to all individuals with newly diagnosed colorectal cancer, with the intent of reducing morbidity and mortality in family members. To explore issues surrounding implementation of this recommendation, the Centers for Disease Control and Prevention convened a multidisciplinary working group meeting in September 2010. This article reviews background information regarding screening for Lynch syndrome and summarizes existing clinical paradigms, potential implementation strategies, and conclusions which emerged from the meeting. It was recognized that widespread implementation will present substantial challenges, and additional data from pilot studies will be needed. However, evidence of feasibility and population health benefits and the advantages of considering a public health approach were acknowledged. Lynch syndrome can potentially serve as a model to facilitate the development and implementation of population-level programs for evidence-based genomic medicine applications involving follow-up testing of at-risk relatives. Such endeavors will require multilevel and multidisciplinary approaches building on collaborative public health and clinical partnerships.

Public Health Action in Genomics Is Now Needed beyond Newborn Screening

“…Also, there are privacy concerns when cascade screening is used to contact the relatives of a patient who has already been diagnosed or is known to have a specific genetic condition. Unlike the case with NBS, there are no universal screening programs in the US to identify people recommended for these applications; nor at present can the case be made for population screening of these applications in the US in the absence of pilot or demonstration programs to show scalability and effectiveness in the real world [10]. Further, many who should have the test may not have the resources to pay for either the genetic testing or the follow-up treatments or screenings which might be indicated.…”

“…These registries can be used to integrate information on hereditary breast, ovarian and CRC to track progress in implementation of tier 1 genomic applications [10]. …”

“…Projects for LS and CRC conducted at Ohio State University already provide some lessons learned. Ohio State University was among the first centers to demonstrate the feasibility of screening all newly diagnosed CRC cases for LS [10]. Experience gained from such initial efforts can be exported through shared protocols.…”

“…Mutations in mismatch repair (MMR) genes confer a lifetime CRC risk of 54–74% in males and 30–52% in females, and screening colonoscopy at 1- to 3-year intervals among people with LS can reduce risk by about 60%. Based on the number of CRC cases diagnosed in the US in 2007 alone (143,000), an estimated 4,200 cases were due to LS [10]. LS may affect as many as 800,000 people in the US, and an estimated 98% of these people may be undiagnosed [20].…”

“…The Evaluation of Genomic Applications in Practice and Prevention recommends that genetic testing for LS be offered to all persons with newly diagnosed CRC and that cascade screening then be used to reach relatives, creating a unique opportunity to prevent CRC, through increased surveillance where indicated, in thousands of people using relatively inexpensive tests [8,10]. Furthermore, an analysis conducted in 2009 found that this cascading approach is cost effective – being at least comparable with other preventive services [21].…”