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American founder mutation for Lynch syndrome
Author(s) -
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 YunXin,
Haynatzki Gleb R.,
Gong Gordon
Publication year - 2005
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.21624
Subject(s) - lynch syndrome , founder effect , genetics , population , incidence (geometry) , mutation , medicine , cancer , biology , dna mismatch repair , allele , gene , colorectal cancer , physics , environmental health , optics , haplotype
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. Cancer 2006. © 2005 American Cancer Society.