BACKGROUND: Recently, a new founder mutation, an exon 1-6 deletion in a mismatch repair gene (MMR), MSH2, in nine kindreds with Lynch syndrome was reported. In 3 of the kindreds this mutation was traced by genealogy through 11-12 generations to a common founder, and thus termed the American Founder Mutation (AFM). Since then, 13 additional 'unrelated' kindreds with AFM were detected by a recently designed single polymerase chain reaction. This test might serve as first-line screening for Lynch syndrome mutations, provided AFM was prevalent, which is assessed in the current study. METHODS: The number of current AFM carriers and the incidence of Lynch syndrome caused by AFM were estimated based on population growth of mutation carriers derived from genealogy data. For cross-checking, its annual incidence was also estimated based on published epidemiology data. RESULTS: There are 18,981 (5th and 95th percentiles, 6038 and 34,466, respectively) expected current AFM carriers, or 160 (range 51-290) Lynch syndrome cases diagnosed per year due to AFM estimated based on genealogy data. The incidence estimate closely overlaps with that based on published epidemiology data, which is 114-400 cases per year. CONCLUSIONS: A large number of AFM carriers are likely to exist in the U.S., which harbors significant implications for cancer control. Given the ease of detection, testing for AFM not only among members of the existing AFM families, but also among all patients with Lynch syndrome in the U.S. is proposed.
BACKGROUND: Recently, a new founder mutation, an exon 1-6 deletion in a mismatch repair gene (MMR), MSH2, in nine kindreds with Lynch syndrome was reported. In 3 of the kindreds this mutation was traced by genealogy through 11-12 generations to a common founder, and thus termed the American Founder Mutation (AFM). Since then, 13 additional 'unrelated' kindreds with AFM were detected by a recently designed single polymerase chain reaction. This test might serve as first-line screening for Lynch syndrome mutations, provided AFM was prevalent, which is assessed in the current study. METHODS: The number of current AFM carriers and the incidence of Lynch syndrome caused by AFM were estimated based on population growth of mutation carriers derived from genealogy data. For cross-checking, its annual incidence was also estimated based on published epidemiology data. RESULTS: There are 18,981 (5th and 95th percentiles, 6038 and 34,466, respectively) expected current AFM carriers, or 160 (range 51-290) Lynch syndrome cases diagnosed per year due to AFM estimated based on genealogy data. The incidence estimate closely overlaps with that based on published epidemiology data, which is 114-400 cases per year. CONCLUSIONS: A large number of AFM carriers are likely to exist in the U.S., which harbors significant implications for cancer control. Given the ease of detection, testing for AFM not only among members of the existing AFM families, but also among all patients with Lynch syndrome in the U.S. is proposed.
Authors: Henry T Lynch; Murray Joseph Casey; Carrie L Snyder; Chhanda Bewtra; Jane F Lynch; Matthew Butts; Andrew K Godwin Journal: Mol Oncol Date: 2009-02-21 Impact factor: 6.603
Authors: I Kedar; L Walsh; G Reznick Levi; S Lieberman; A Abu Shtaya; S Naftaly Nathan; I Lagovsky; R Tomashov-Matar; M Goldenberg; L Basel-Salmon; L Katz; O Aleme; T Yablonski Peretz; A Hubert; D Rothstein; S Castellvi-Bel; T Walsh; M C King; C C Pritchard; Z Levi; E Half; I Laish; Y Goldberg Journal: Fam Cancer Date: 2021-04-10 Impact factor: 2.375
Authors: Jose Miguel Moreno-Ortiz; María de la Luz Ayala-Madrigal; Jorge Román Corona-Rivera; Manuel Centeno-Flores; Víctor Maciel-Gutiérrez; Ramón Antonio Franco-Topete; Juan Armendáriz-Borunda; Erin Hotchkiss; Lucia Pérez-Carbonell; Jennifer Rhees; Clement Richard Boland; Melva Gutiérrez-Angulo Journal: Gastroenterol Res Pract Date: 2016-05-10 Impact factor: 2.260