Associations between intake of folate and related micronutrients with molecularly defined colorectal cancer risks in the Iowa Women's Health Study.
Folate and related micronturients may affect colorectal cancer (CRC) risk, but the molecular mechanism(s) remain incompletely defined. We analyzed associations between dietary folate, vitamin B6, vitamin B12, and methionine with incident CRC, overall and by microsatellite instability (MSS/MSI-L or MSI-H), CpG island methylator phenotype (CIMP-negative or CIMP-positive), BRAF mutation (negative or positive), and KRAS mutation (negative or positive) status in the prospective, population-based Iowa Women's Health Study (IWHS; 55-69 years at baseline; n = 41,836). Intake estimates were obtained from baseline, self-reported food frequency questionnaires. Molecular marker data were obtained for 514 incident CRC cases. Folate intake was inversely associated with overall CRC risk in age-adjusted Cox regression models, whereas methionine intake was inversely associated with overall CRC risk in multivariable-adjusted models [relative risk (RR) = 0.81; 95% CI = 0.69-0.95; P trend = 0.001 and RR = 0.72; 95% CI = 0.54-0.96; P trend = 0.03 for highest vs. lowest quartiles, respectively]. None of the dietary exposures were associated with MSI, CIMP, BRAF, or KRAS defined CRC subtypes. These data provide minimal support for major effects from the examined micronutrients on overall or molecularly defined CRC risks in the IWHS cohort.
Department of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
Anthony A
AA
Razzak
Amy S
AS
Oxentenko
Robert A
RA
Vierkant
Lori S
LS
Tillmans
Alice H
AH
Wang
Daniel J
DJ
Weisenberger
Peter W
PW
Laird
Charles F
CF
Lynch
Kristin E
KE
Anderson
Amy J
AJ
French
Robert W
RW
Haile
Lisa J
LJ
Harnack
John D
JD
Potter
Susan L
SL
Slager
Thomas C
TC
Smyrk
Stephen N
SN
Thibodeau
James R
JR
Cerhan
Paul J
PJ
Limburg
D000368:Aged; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D005247:Feeding Behavior; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D005500:Follow-Up Studies; D005819:Genetic Markers; D006801:Humans; D015994:Incidence; D007484:Iowa / Q000453:epidemiology; D008019:Life Style; D018977:Micronutrients / Q000008:administration & dosage*; D053842:Microsatellite Instability; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009749:Nutrition Surveys; D010641:Phenotype; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D012307:Risk Factors; D011795:Surveys and Questionnaires; D014805:Vitamin B 12 / Q000008:administration & dosage; D025101:Vitamin B 6 / Q000008:administration & dosage; D016387:Women's Health; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
D005819:Genetic Markers; C117307:KRAS protein, human; D018977:Micronutrients; D011518:Proto-Oncogene Proteins; D025101:Vitamin B 6; D005492:Folic Acid; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D014805:Vitamin B 12