Diet and lifestyle factor associations with CpG island methylator phenotype and BRAF mutations in colon cancer
Corresponding Author
Martha L. Slattery
Department of Internal Medicine, Salt Lake City, UT
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.
Fax: +-801-581-3623.
Department of Internal Medicine, 375 Chipeta Way, Suite A, Salt Lake City, UT 84108, USASearch for more papers by this authorKaren Curtin
Department of Internal Medicine, Salt Lake City, UT
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.
Search for more papers by this authorCarol Sweeney
Department of Internal Medicine, Salt Lake City, UT
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.
Search for more papers by this authorTheodore R. Levin
Kaiser Permanente Medical Center, Walnut Creek, CA
Search for more papers by this authorJohn Potter
Fred Hutchinson Cancer Research Center, Seattle, WA
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.
Search for more papers by this authorRoger K. Wolff
Department of Internal Medicine, Salt Lake City, UT
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.
Search for more papers by this authorHans Albertsen
Department of Internal Medicine, Salt Lake City, UT
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.
Search for more papers by this authorWade S. Samowitz
Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, UT
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.
Search for more papers by this authorCorresponding Author
Martha L. Slattery
Department of Internal Medicine, Salt Lake City, UT
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.
Fax: +-801-581-3623.
Department of Internal Medicine, 375 Chipeta Way, Suite A, Salt Lake City, UT 84108, USASearch for more papers by this authorKaren Curtin
Department of Internal Medicine, Salt Lake City, UT
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.
Search for more papers by this authorCarol Sweeney
Department of Internal Medicine, Salt Lake City, UT
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.
Search for more papers by this authorTheodore R. Levin
Kaiser Permanente Medical Center, Walnut Creek, CA
Search for more papers by this authorJohn Potter
Fred Hutchinson Cancer Research Center, Seattle, WA
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.
Search for more papers by this authorRoger K. Wolff
Department of Internal Medicine, Salt Lake City, UT
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.
Search for more papers by this authorHans Albertsen
Department of Internal Medicine, Salt Lake City, UT
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.
Search for more papers by this authorWade S. Samowitz
Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, UT
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.
Search for more papers by this authorFax: +-801-581-3623.
Abstract
It has been proposed that dietary factors such as folate, alcohol and methionine may be associated with colon cancer because of their involvement in DNA methylation processes. Data from a large population-based case-control study of incident colon cancer were used to evaluate whether intake of dietary, obesity, physical activity and nonsteroidal antiinflammatory drugs are associated with a CpG island methylator phenotype (CIMP). The BRAF V600E mutation and 5 CpG island markers (MINT1, MINT2, MINT31, p16 and hMLH1) were assessed in 1154 cases of colon cancer. We hypothesized that dietary factors involved in DNA methylation, cruciferous vegetables and use of aspirin/NSAIDs would be associated with CIMP-high tumors. Dietary folate, vitamins B6 and B12, methionine and alcohol were not associated with increased likelihood of colon tumors with the CIMP-high (2 or more markers methylated) phenotype. Dietary fiber, physical activity and aspirin and other nonsteroidal antiinflammatory drugs were inversely associated with both CIMP-low and CIMP-high tumors. Our results also suggested non-CIMP pathways as well. Obese individuals were at 2-fold increased risk of having a CIMP-low tumor. Alcohol was associated with an increased risk of tumors that were MSI+ and CIMP-low. In the presence of smoking 20 or more cigarettes per day, use of NSAIDs did not protect against a BRAF mutation. Our data suggest multiple pathways to colon cancer. They do not support a unique role for dietary folate, alcohol, vitamins B6 and B12 and methionine in a CpG island methylator phenotype. © 2006 Wiley-Liss, Inc.
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