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We thank J. Lutterbaugh, E. Lawrence, and L. Beard for assistance with cell culture and DNA preparation; K. Makowski and the Agencourt sequencing team for assistance with automated sequencing; C.-S. Liu and the SoftGenetics team for their assistance with mutation detection analyses; and D. H. Nguyen of the Johns Hopkins Department of Art as Applied to Medicine for the artwork in Fig. 3. Supported by The Virginia and D. K. Ludwig Fund for Cancer Research; NIH grants CA121113, CA 43460, CA 57345, CA62924, GM07309, RR017698, P30-CA43703, CA109274, GM070219, and CA112828; NCI Division of Cancer Prevention contract HHSN261200433002C; Department of Defense grant DAMD17-03-1-0241; NSF grant DMS034211; The Pew Charitable Trusts; The Palmetto Health Foundation; The Maryland Cigarette Restitution Fund; The State of Ohio Biomedical Research and Technology Transfer Commission; The Clayton Fund; The Blaustein Foundation; The National Colorectal Cancer Research Alliance; the Strang Cancer Prevention Center; the Division of Cancer Prevention of the National Cancer Institute; the Avon Foundation; The Flight Attendant's Medical Research Institute; the V Foundation for Cancer Research; the Summer Running Fund; and The Palmetto Health Foundation. Under separate licensing agreements between the Johns Hopkins University and Genzyme Corporation and Exact Sciences Corporation, K.W.K., B.V., and V.E.V. are entitled to a share of royalties received by the University on sales of products related to research described in this paper. These authors and the University own Genzyme stock, which is subject to certain restrictions under University policy. The terms of these arrangements are managed by the Johns Hopkins University in accordance with its conflict-of-interest policies.