title: Dietary fat and risk of colon and rectal cancer with aberrant MLH1 expression, APC or KRAS genes.
abstract: OBJECTIVE
  To investigate baseline fat intake and the risk of colon and rectal tumors lacking MLH1 (mutL homolog 1, colon cancer, nonpolyposis type 2) repair gene expression and harboring mutations in the APC (adenomatous polyposis coli) tumor suppressor gene and in the KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) oncogene.
  
  
  METHODS
  After 7.3 years of follow-up of the Netherlands Cohort Study (n = 120,852), adjusted incidence rate ratios (RR) and 95% confidence intervals (CI) were computed, based on 401 colon and 130 rectal cancer patients.
  
  
  RESULTS
  Total, saturated and monounsaturated fat were not associated with the risk of colon or rectal cancer, or different molecular subgroups. There was also no association between polyunsaturated fat and the risk of overall or subgroups of rectal cancer. Linoleic acid, the most abundant polyunsaturated fatty acid in the diet, was associated with increased risk of colon tumors with only a KRAS mutation and no additional truncating APC mutation or lack of MLH1 expression (RR = 1.41, 95% CI 1.18-1.69 for one standard deviation (i.e., 7.5 g/day) increase in intake, p-trend over the quartiles of intake <0.001). Linoleic acid intake was not associated with risk of colon tumors without any of the gene defects, or with tumors harboring aberrations in either MLH1 or APC.
  
  
  CONCLUSIONS
  Linoleic acid intake is associated with colon tumors with an aberrant KRAS gene, but an intact APC gene and MLH1 expression, suggesting a unique etiology of tumors with specific genetic aberrations.
authors.affiliation: Department of Epidemiology, Nutrition and Toxicology Research Institute Maastricht, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands mp.weijenberg@epid.unimaas.nl
authors.forename: Matty P
authors.initials: MP
authors.lastname: Weijenberg
authors.forename: Margreet
authors.initials: M
authors.lastname: Lüchtenborg
authors.forename: Anton F P M
authors.initials: AF
authors.lastname: de Goeij
authors.forename: Mirian
authors.initials: M
authors.lastname: Brink
authors.forename: Goos N P
authors.initials: GN
authors.lastname: van Muijen
authors.forename: Adriaan P
authors.initials: AP
authors.lastname: de Bruïne
authors.forename: R Alexandra
authors.initials: RA
authors.lastname: Goldbohm
authors.forename: Piet A
authors.initials: PA
authors.lastname: van den Brandt
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics*; D000368:Aged; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D004032:Diet; D004041:Dietary Fats / Q000008:administration & dosage*; D005260:Female; D005500:Follow-Up Studies; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009154:Mutation / Q000235:genetics*; D009426:Netherlands / Q000453:epidemiology; D009687:Nuclear Proteins / Q000235:genetics*; D011446:Prospective Studies
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D025601:Adenomatous Polyposis Coli Protein; D004041:Dietary Fats; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1