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American founder mutation for Lynch syndrome. Prevalence estimates and implications
Henry T Lynch1, Albert de la Chapelle, Heather Hampel
1Department of Preventive Medicine and Public Health, Creighton University, Omaha, Nebraska 68178, USA. htlynch@creighton.edu
Cancer
|December 15, 2005
Summary
The American Founder Mutation (AFM) in MSH2 may cause Lynch syndrome. This study estimates over 18,000 AFM carriers in the U.S., suggesting widespread screening is needed for cancer control.
Area of Science:
- Genetics
- Cancer Epidemiology
- Molecular Biology
Background:
- A novel MSH2 exon 1-6 deletion, the American Founder Mutation (AFM), has been identified in Lynch syndrome kindreds.
- Genealogy traced AFM in some families to an 11-12 generation common founder.
- A single polymerase chain reaction (PCR) test has since detected AFM in additional "unrelated" kindreds.
Purpose of the Study:
- To assess the prevalence of the American Founder Mutation (AFM) in the U.S. population.
- To determine if AFM is common enough to warrant its use as a first-line Lynch syndrome screening test.
Main Methods:
- Estimated current AFM carriers and Lynch syndrome incidence using population growth models from genealogy data.
- Cross-validated incidence estimates with published epidemiological data.
Main Results:
- An estimated 18,981 current AFM carriers (5th-95th percentiles: 6038-34,466) are predicted in the U.S.
- An estimated 160 Lynch syndrome cases (range: 51-290) per year are attributed to AFM, aligning with epidemiological data (114-400 cases/year).
Conclusions:
- A substantial number of American Founder Mutation carriers likely reside in the U.S., impacting cancer control strategies.
- Widespread testing for AFM is recommended for Lynch syndrome patients, not just within known AFM families, due to its ease of detection.
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