American Founder Mutation for Lynch syndrome: Prevalence estimates and implications

Henry T. Lynch, Albert De La Chapelle, Heather Hampel, Anja Wagner, Riccardo Fodde, Jane F. Lynch, Ross Okimoto, Mary Beth Clark, Stephanie Coronel, Abdon Trowonou, Yun Xin Fu, Gleb R. Haynatzki, Gordon Gong

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


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. COMCLUSIONS. 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.

Original languageEnglish (US)
Pages (from-to)448-452
Number of pages5
Issue number2
StatePublished - Jan 15 2006
Externally publishedYes


  • Carrier
  • Colorectal carcinoma
  • Founder mutation
  • Lynch syndrome

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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