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 journalArticle

12 Citations (Scopus)

Abstract

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
Pages (from-to)448-452
Number of pages5
JournalCancer
Volume106
Issue number2
DOIs
StatePublished - Jan 15 2006

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Hereditary Nonpolyposis Colorectal Neoplasms
Mutation
Genealogy and Heraldry
Incidence
Epidemiology
DNA Mismatch Repair
Population Growth

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Oncology

Cite this

Lynch, H. T., De La Chapelle, A., Hampel, H., Wagner, A., Fodde, R., Lynch, J. F., ... Gong, G. (2006). American Founder Mutation for Lynch syndrome: Prevalence estimates and implications. Cancer, 106(2), 448-452. https://doi.org/10.1002/cncr.21624

American Founder Mutation for Lynch syndrome : Prevalence estimates and implications. / Lynch, Henry T.; De La Chapelle, Albert; Hampel, Heather; Wagner, Anja; Fodde, Riccardo; Lynch, Jane F.; Okimoto, Ross; Clark, Mary Beth; Coronel, Stephanie; Trowonou, Abdon; Fu, Yun Xin; Haynatzki, Gleb R.; Gong, Gordon.

In: Cancer, Vol. 106, No. 2, 15.01.2006, p. 448-452.

Research output: Contribution to journalArticle

Lynch, HT, De La Chapelle, A, Hampel, H, Wagner, A, Fodde, R, Lynch, JF, Okimoto, R, Clark, MB, Coronel, S, Trowonou, A, Fu, YX, Haynatzki, GR & Gong, G 2006, 'American Founder Mutation for Lynch syndrome: Prevalence estimates and implications', Cancer, vol. 106, no. 2, pp. 448-452. https://doi.org/10.1002/cncr.21624
Lynch HT, De La Chapelle A, Hampel H, Wagner A, Fodde R, Lynch JF et al. American Founder Mutation for Lynch syndrome: Prevalence estimates and implications. Cancer. 2006 Jan 15;106(2):448-452. https://doi.org/10.1002/cncr.21624
Lynch, Henry T. ; De La Chapelle, Albert ; Hampel, Heather ; Wagner, Anja ; Fodde, Riccardo ; Lynch, Jane F. ; Okimoto, Ross ; Clark, Mary Beth ; Coronel, Stephanie ; Trowonou, Abdon ; Fu, Yun Xin ; Haynatzki, Gleb R. ; Gong, Gordon. / American Founder Mutation for Lynch syndrome : Prevalence estimates and implications. In: Cancer. 2006 ; Vol. 106, No. 2. pp. 448-452.
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abstract = "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.",
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N2 - 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.

AB - 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.

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