Diet and lifestyle factor associations with CpG island methylator phenotype and BRAF mutations in colon cancer.
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 B(6) and B(12), 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 B(6) and B(12) and methionine in a CpG island methylator phenotype.
Slattery
Martha L
ML
Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, UT 84108, USA. mslatter@hrc.utah.edu
Curtin
Karen
K
Sweeney
Carol
C
Levin
Theodore R
TR
Potter
John
J
Wolff
Roger K
RK
Albertsen
Hans
H
Samowitz
Wade S
WS
D000328:Adult; D000368:Aged; D000428:Alcohol Drinking; D016022:Case-Control Studies; D003110:Colonic Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000473:pathology*; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D004032:Diet; D005260:Female; D006801:Humans; D008019:Life Style; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D008910:Minnesota / Q000453:epidemiology; D009154:Mutation / Q000235:genetics; D020125:Mutation, Missense / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking; D014589:Utah / Q000453:epidemiology; D014861:Washington / Q000453:epidemiology
D004273:DNA, Neoplasm; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf