B-vitamin intake, metabolic genes, and colorectal cancer risk (United States).
OBJECTIVE
This population-based case-control study was designed to investigate the interrelationships between polymorphisms in the methylenetetrahydrofolate (MTHFR C677T and A1298C) gene and other genes (MTR A2756G; MTRR A66G and CBS 844ins68), intake of B-vitamins and colorectal cancer risk (CRC).


METHODS
We interviewed 727 CRC cases of Japanese, Caucasian, or Native Hawaiian origin and 727 controls matched on sex, age, and ethnicity.


RESULTS
Compared to the homozygous wild-type genotype, the odds ratios for subjects with one or two MTHFR 677T variant alleles were 0.8 (0.6-1.1) and 0.7 (0.5-1.1), respectively (p for gene-dosage effect: 0.04). The TT genotype was associated with a 50-60% decrease in CRC risk among subjects with high intake of folate or vitamin B6, compared to those with the CC genotype and low levels of intake. The MTHFR 1298C and CBS8 44ins68 variant alleles were also found to be weakly protective against CRC and to act jointly with the 677T allele.


CONCLUSIONS
This study provides additional evidence for a decreased CRC risk for subjects with the MTHFR 677T allele, particularly at high levels of folate and vitamin B6 intake. Our data also suggest that the relationships between CRC and the MTHFR A1298C and CBS 844ins68 polymorphisms warrant further study.
Le Marchand
Loïc
L
Etiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu 96813, USA.
Donlon
Timothy
T
Hankin
Jean H
JH
Kolonel
Laurence N
LN
Wilkens
Lynne R
LR
Seifried
Ann
A
D017677:Age Distribution; D000368:Aged; D001483:Base Sequence; D015982:Bias; D016022:Case-Control Studies; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000517:prevention & control; D003541:Cystathionine beta-Synthase / Q000235:genetics; D003626:Data Display; D019587:Dietary Supplements; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D015994:Incidence; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D018895:Microsatellite Repeats; D008875:Middle Aged; D008969:Molecular Sequence Data; D016017:Odds Ratio; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011336:Probability; D012016:Reference Values; D018570:Risk Assessment; D017678:Sex Distribution; D014481:United States / Q000453:epidemiology; D025101:Vitamin B 6 / Q000008:administration & dosage*
D025101:Vitamin B 6; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D003541:Cystathionine beta-Synthase