The American founder mutation for Lynch syndrome: Prevalence and cancer control implications

9505 Background: We have recently reported a new founder mutation, namely, an exon 1–6 deletion in the MSH2 gene detectable by a recently designed single PCR reaction in 9 kindreds with Lynch Syndrome. In 3 of the kindreds this mutation has been traced through genealogy 12 to 13 generations back to a common founder and thus termed the American Founder Mutation (AFM). We have since identified 11 additional apparently unrelated kindreds with AFM. The new PCR test might serve as first-line screening for Lynch syndrome provided the mutation were prevalent and widespread, which we assess in this study. Methods: With the genealogy data, the expected number of AFM carriers at generation k is E(mk)= mk-1sk/2, where k is number of generations that had passed since the founder had settled in the US, and skis the number of reproductive offspring per mutation carrier at generation k-1. The 95% C.I. was computed based on the probability distribution of mk with simulation of 1 million replicates. From E(mk) we estimate...