title: Counterpoint: implementing population genetic screening for Lynch Syndrome among newly diagnosed colorectal cancer patients--will the ends justify the means?
abstract: Inherited mutations in 1 of 4 known mismatch repair genes (MLH1, MSH2, MSH6, PMS2) are associated with various cancer risks collectively referred to as Lynch syndrome. Roughly 3 of every 100 new colorectal cancers (CRCs) have an underlying Lynch mutation. Tumor-based screening for Lynch among all patients with newly diagnosed CRC could theoretically improve the ability to identify Lynch and prevent cancer among at-risk family members, but the patient-level and social implications of this approach must be carefully considered before adopting this strategy. Poorly addressed issues include the role/timing of informed consent for testing, access and cost barriers associated with genetic counseling and DNA testing, psychosocial burdens to the thousands of middle-aged and elderly patients with CRC coping with surgical and chemotherapy treatments and poor prognosis, the need for providers to warn third-party relatives of risk for Lynch syndrome, limited effectiveness of screening, and the cost burden to society when poor DNA testing uptake, test limitations, and modest screening compliance are considered. Diverse barriers to the success of a population-based Lynch screening program in the United States remain (e.g., clinical resource needs, financial limitations, clinical expertise gaps, educational deficits). Data supporting clinical efficacy (feasibility) and effectiveness (real-life performance) are critical before important policy changes are adopted, especially where issues of hereditary cancer risk and genetic privacy are involved.
authors.affiliation: Medical Oncology and Cancer Prevention and Control, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA. michael.hall@fccc.edu
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hall
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000251:Adenosine Triphosphatases / Q000235:genetics; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D053843:DNA Mismatch Repair; D045643:DNA Repair Enzymes / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D003657:Decision Making; D055088:Early Detection of Cancer; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005828:Genetics, Population; D006801:Humans; D007150:Immunohistochemistry; D053842:Microsatellite Instability; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D011379:Prognosis; D018570:Risk Assessment; D014481:United States / Q000453:epidemiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; C497172:MSH2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D045643:DNA Repair Enzymes