title: Dietary folate intake and k-ras mutations in sporadic colon and rectal cancer in The Netherlands Cohort Study.
abstract: We studied the association between dietary folate and specific K-ras mutations in colon and rectal cancer in The Netherlands Cohort Study on diet and cancer. After 7.3 years of follow-up, 448 colon and 160 rectal cancer patients and 3,048 sub-cohort members (55-69 years at baseline) were available for data analyses. Mutation analysis of the K-ras gene was carried out on all archival adenocarcinoma specimens. Case-cohort analyses were used to compute adjusted incidence rate ratios (RR) and 95% confidence intervals (CI) for colon and rectal cancer overall and for K-ras mutation status subgroups according to 100 mug/day increased intake in dietary folate. Dietary folate intake was not significantly associated with colon cancer risk for men or women, neither overall nor with K-ras mutation status. For rectal cancer, folate intake was associated with a decreased disease risk in men and was most pronounced for K-ras mutated tumors, whereas an increased association was observed for women. Regarding the K-ras mutation status in women, an increased association was observed for both wild-type and mutated K-ras tumors. Specifically, folate intake was associated with an increased risk of G>T and G>C transversions in rectal tumors (RR = 2.69, 95% CI = 1.43-5.09), but inversely associated with G>A transitions (RR = 0.08, 95% CI = 0.01-0.53). Our data suggest that the effect of folate on rectal cancer risk is different for men and women and depends on the K-ras mutation status of the tumor.
authors.affiliation: Research Institute Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Department of Epidemiology, Maastricht University, Maastricht, The Netherlands.
authors.forename: Mirian
authors.initials: M
authors.lastname: Brink
authors.forename: Matty P
authors.initials: MP
authors.lastname: Weijenberg
authors.forename: Anton F P M
authors.initials: AF
authors.lastname: de Goeij
authors.forename: Guido M J M
authors.initials: GM
authors.lastname: Roemen
authors.forename: Marjolein H F M
authors.initials: MH
authors.lastname: Lentjes
authors.forename: Adriaan P
authors.initials: AP
authors.lastname: de Bruïne
authors.forename: Manon
authors.initials: M
authors.lastname: van Engeland
authors.forename: R Alexandra
authors.initials: RA
authors.lastname: Goldbohm
authors.forename: Piet A
authors.initials: PA
authors.lastname: van den Brandt
mesh_terms: D000368:Aged; D015331:Cohort Studies; D003110:Colonic Neoplasms / Q000209:etiology / Q000235:genetics*; D004252:DNA Mutational Analysis; D004032:Diet; D005260:Female; D005492:Folic Acid / Q000378:metabolism*; D011905:Genes, ras; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009369:Neoplasms / Q000378:metabolism; D009426:Netherlands; D012004:Rectal Neoplasms / Q000209:etiology / Q000235:genetics*; D012306:Risk; D012737:Sex Factors
chemical_list: D005492:Folic Acid