Alimentary TractThe colon cancer burden of genetically defined hereditary nonpolyposis colon cancer☆,☆☆,★
Section snippets
Study population
This population-based sample was originally collected as part of an epidemiologic study of colon cancer.22 Study participants identified themselves as black (7.2%), white (86.3%), or Hispanic (6.5%) and were from either the Kaiser Permanente Medical Care Program (KPMCP) of Northern California or an 8-county area in Utah (Davis, Salt Lake, Utah, Weber, Wasatch, Tooele, Morgan, and Summit counties). The associated clinical and pathologic features of these individuals and their colon cancers have
Results
Microsatellite instability was identified in 14% (131/933) of tumors with a panel of 10 tetranucleotide repeats, 13% (130/1001) of tumors with BAT-26, and 11.4% (116/1018) of tumors with TGFβRII. Sixteen percent of tumors (171/1066) were identified as unstable by at least one of these measures of instability.
Germline sequencing of the 130 individuals with unstable tumors and with sufficient DNA for sequencing (see Materials and Methods) revealed 7 probable HNPCC mutations, including 5
Discussion
This study represents the first attempt to identify at the genetic level the colon cancer burden associated with HNPCC in the United States. We identified HNPCC-causing germline mutations in 7 individuals; after adjusting for the availability of sufficient germline DNA for sequencing (see Materials and Methods), this corresponded to 0.86% of colon cancer at the population level.
We also identified missense changes of less certain significance in an additional 12 individuals. Although most
Acknowledgements
The authors thank Dr. Bette Caan, Judy Morse, Sandra Edwards, and Leslie Palmer for their data collection and tissue processing efforts, and the genomics core facility for its assistance in genotyping.
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Address requests for reprints to: Wade S. Samowitz, M.D., Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah 84132. e-mail: [email protected]; fax: (801) 585-3831.
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Supported by grants CA48998 and CA61757 (to M.L.S.), and by the Utah Cancer Registry, which is funded by Contract #N01-PC-67000 from the National Cancer Institute, with additional support from the State of Utah Department of Health and the University of Utah, the Northern California Cancer Registry, and the Sacramento Tumor Registry.
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The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official view of the National Cancer Institute.