title: Universal Versus Targeted Screening for Lynch Syndrome: Comparing Ascertainment and Costs Based on Clinical Experience.
abstract: Strategies to screen colorectal cancers (CRCs) for Lynch syndrome are evolving rapidly; the optimal strategy remains uncertain.
  
  
  
  We compared targeted versus universal screening of CRCs for Lynch syndrome.
  
  
  
  In 2010-2011, we employed targeted screening (age < 60 and/or Bethesda criteria). From 2012 to 2014, we screened all CRCs. Immunohistochemistry for the four mismatch repair proteins was done in all cases, followed by other diagnostic studies as indicated. We modeled the diagnostic costs of detecting Lynch syndrome and estimated the 5-year costs of preventing CRC by colonoscopy screening, using a system dynamics model.
  
  
  
  Using targeted screening, 51/175 (29 %) cancers fit criteria and were tested by immunohistochemistry; 15/51 (29 %, or 8.6 % of all CRCs) showed suspicious loss of ≥1 mismatch repair protein. Germline mismatch repair gene mutations were found in 4/4 cases sequenced (11 suspected cases did not have germline testing). Using universal screening, 17/292 (5.8 %) screened cancers had abnormal immunohistochemistry suspicious for Lynch syndrome. Germline mismatch repair mutations were found in only 3/10 cases sequenced (7 suspected cases did not have germline testing). The mean cost to identify Lynch syndrome probands was ~$23,333/case for targeted screening and ~$175,916/case for universal screening at our institution. Estimated costs to identify and screen probands and relatives were: targeted, $9798/case and universal, $38,452/case.
  
  
  
  In real-world Lynch syndrome management, incomplete clinical follow-up was the major barrier to do genetic testing. Targeted screening costs 2- to 7.5-fold less than universal and rarely misses Lynch syndrome cases. Future changes in testing costs will likely change the optimal algorithm.
authors.affiliation: Department of Surgery, Global Health Economics Unit, Center for Clinical and Translational Science, University of Vermont College of Medicine, Courtyard at Given S354, 89 Beaumont Avenue, Burlington, VT, 05405, USA.
authors.forename: Mujde Z
authors.initials: MZ
authors.lastname: Erten
authors.affiliation: Community Development and Public Administration and Policy, University of Vermont, 102 Morrill Hall, Burlington, VT, 05405, USA.
authors.forename: Luca P
authors.initials: LP
authors.lastname: Fernandez
authors.affiliation: Internal Medicine, University of Vermont Medical Center, 111 Colchester Avenue, Burlington, VT, 05401, USA.
authors.forename: Hank K
authors.initials: HK
authors.lastname: Ng
authors.affiliation: University of Vermont Medical Center, 112 Colchester Avenue Barney Building, Burlington, VT, 05401, USA.
authors.forename: Wendy C
authors.initials: WC
authors.lastname: McKinnon
authors.affiliation: Genomic Medicine Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.
authors.forename: Brandie
authors.initials: B
authors.lastname: Heald
authors.affiliation: Community Development and Public Administration and Policy, Gund Institute for Ecological Economics, University of Vermont, 103 Morrill Hall, Burlington, VT, 05405, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Koliba
authors.affiliation: Hematology/Oncology Division, Department of Medicine, University of Vermont College of Medicine, Given Suite E214, 89 Beaumont Avenue, Burlington, VT, 05405, USA. marc.greenblatt@vtmednet.org.
authors.forename: Marc S
authors.initials: MS
authors.lastname: Greenblatt
mesh_terms: D000367:Age Factors; D003113:Colonoscopy / Q000191:economics*; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000191:economics / Q000235:genetics* / Q000517:prevention & control; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis / Q000191:economics / Q000235:genetics*; D053843:DNA Mismatch Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D055088:Early Detection of Cancer; D005820:Genetic Testing / Q000191:economics*; D018095:Germ-Line Mutation; D017048:Health Care Costs; D006801:Humans; D007150:Immunohistochemistry / Q000191:economics*; D008403:Mass Screening / Q000191:economics; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2 / Q000235:genetics; D000070957:MutL Protein Homolog 1 / Q000235:genetics; D051718:MutS Homolog 2 Protein / Q000235:genetics; D018579:Patient Selection; D013597:Systems Analysis; D014481:United States
chemical_list: D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; C094934:PMS2 protein, human; C497172:MSH2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein
keywords: Colorectal carcinoma; Cost analysis; Lynch syndrome; System dynamics; Universal screening