Dietary folate intake and k-ras mutations in sporadic colon and rectal cancer in The Netherlands Cohort Study.
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.
Brink
Mirian
M
Research Institute Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Department of Epidemiology, Maastricht University, Maastricht, The Netherlands.
Weijenberg
Matty P
MP
de Goeij
Anton F P M
AF
Roemen
Guido M J M
GM
Lentjes
Marjolein H F M
MH
de Bruïne
Adriaan P
AP
van Engeland
Manon
M
Goldbohm
R Alexandra
RA
van den Brandt
Piet A
PA
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
D005492:Folic Acid