Clinical–alimentary tractDietary Factors and Biomarkers Involved in the Methylenetetrahydrofolate Reductase Genotype–Colorectal Adenoma Pathway
Section snippets
Study Populations
Analyses were conducted in participants from the Wheat Bran Fiber and the Ursodeoxycholic Acid trials, the details of which have been reported elsewhere.35, 36, 37 A brief description of each study is provided later. The studies were approved by the University of Arizona Human Subjects Committee and the Institutional Review Board.
The Wheat Bran Fiber trial was a double-blind controlled trial conducted to compare the effect of a high-fiber vs a low-fiber cereal supplement on adenoma recurrence
Results
Among the 1598 individuals genotyped for MTHFR C677T, the prevalence of the T allele was 32.9%; 45.8% were CC homozygotes, 42.7% were heterozygotes, and the remaining 11.5% were TT homozygotes. The corresponding values for the 1583 individuals with MTHFR A1298C data were as follows: 47.3% AA homozygotes, 42.4% heterozygotes, and 10.3% CC homozygotes, with a C allele prevalence of 31.5%. No significant difference in regard to risk factors of interest was observed between this subset of
Discussion
The availability of methyl groups for DNA methylation reactions is regulated primarily by the activity of MTHFR through its role in 1-carbon metabolism. The totality of the published data on the association of MTHFR C677T polymorphism and colorectal cancer indicate that individuals with the TT variant are at lower risk of developing colorectal cancer12; however, the opposite has been shown for other gastrointestinal cancers.48, 49, 50, 51, 52, 53 As well, the carriage of the 677 TT genotype
References (79)
- et al.
Folate and colorectal neoplasia: relationship between plasma and dietary markers of folate and adenoma recurrence
Am J Clin Nutr
(2004) - et al.
A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects?
Am J Hum Genet
(1998) - et al.
A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity
Mol Genet Metab
(1998) - et al.
A common mutation A1298C in human methylenetetrahydrofolate reductase gene: association with plasma total homocysteine and folate concentrations
J Nutr
(1999) - et al.
Adenoma characteristics as risk factors for recurrence of advanced adenomas
Gastroenterology
(2001) - et al.
Genetic polymorphisms in methylenetetrahydrofolate reductase and thymidylate synthase and risk of pancreatic cancer
Clin Gastroenterol Hepatol
(2005) - et al.
Methylenetetrahydrofolate reductase 677C>T polymorphism and gastric cancer susceptibility in Mexico
Eur J Cancer
(2006) - et al.
Effect of MTHFR genotype on diet-induced hyperhomocysteinemia and vascular function in mice
Blood
(2004) - et al.
MTHFR polymorphism, methyl-replete diets and the risk of colorectal carcinoma and adenoma among U.S. men and women: an example of gene-environment interactions in colorectal tumorigenesis
J Nutr
(1999) - et al.
Thermolabile methylenetetrahydrofolate reductase, homocysteine, and cardiovascular disease risk: the European Concerted Action Project
Am J Clin Nutr
(2003)
Determinants of plasma total homocysteine concentration in the Framingham Offspring cohort
Am J Clin Nutr
Increase in plasma homocysteine associated with parallel increases in plasma S-adenosylhomocysteine and lymphocyte DNA hypomethylation
J Biol Chem
Elevation in S-adenosylhomocysteine and DNA hypomethylation: potential epigenetic mechanism for homocysteine-related pathology
J Nutr
Disturbed ratio of erythrocyte and plasma S-adenosylmethionine/S-adenosylhomocysteine in peripheral arterial occlusive disease
Atherosclerosis
Folate intake and colorectal cancer risk: a meta-analytical approach
Int J Cancer
Colorectal cancer and folate status: a nested case-control study among male smokers
Cancer Epidemiol Biomarkers Prev
Serum folate, homocysteine and colorectal cancer risk in women: a nested case-control study
Br J Cancer
Folate deficiency causes uracil misincorporation into human DNA and chromosome breakage: implications for cancer and neuronal damage
Proc Natl Acad Sci U S A
Folic acid deficiency and cancer: mechanisms of DNA instability
Br Med Bull
Human methylenetetrahydrofolate reductase: isolation of cDNA, mapping and mutation identification
Nat Genet
Mutated methylenetetrahydrofolate reductase as a risk factor for spina bifida
Lancet
Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations
Circulation
Genetic determinants of hyperhomocysteinaemia: the roles of cystathionine beta-synthase and 5,10-methylenetetrahydrofolate reductase
Eur J Pediatr
Genetic modulation of homocysteinemia
Semin Thromb Hemost
Genetic polymorphisms of methylenetetrahydrofolate reductase and colorectal cancer and adenoma
Cancer Sci
5,10-methylenetetrahydrofolate reductase common mutations, folate status and plasma homocysteine in healthy French adults of the Supplementation en Vitamines et Mineraux Antioxydants (SU.VI.MAX) cohort
Br J Nutr
A1298C methylenetetrahydrofolate reductase mutation and coronary artery disease: relationships with C677T polymorphism and homocysteine/folate metabolism
Clin Exp Med
Methylenetetrahydrofolate reductase, alcohol dehydrogenase, diet, and risk of colorectal adenomas
Cancer Epidemiol Biomarkers Prev
Methylenetetrahydrofolate reductase polymorphism, dietary interactions and risk of colorectal cancer
Cancer Res
Methylenetetrahydrofolate reductase, diet, and risk of colon cancer
Cancer Epidemiol Biomarkers Prev
The methylenetetrahydrofolate reductase 677C–>T polymorphism and distal colorectal adenoma risk
Cancer Epidemiol Biomarkers Prev
The MTHFR C677T polymorphism and colorectal cancer: the multiethnic cohort study
Cancer Epidemiol Biomarkers Prev
Smoking, folate and methylenetetrahydrofolate reductase status as interactive determinants of adenomatous and hyperplastic polyps of colorectum
Am J Med Genet
Folate intake, MTHFR C677T polymorphism, alcohol consumption, and risk for sporadic colorectal adenoma (United States)
Cancer Causes Control
Colorectal adenomas and the C677T MTHFR Polymorphism: evidence for gene-environment interaction?
Cancer Epidemiol Biomarkers Prev
The effects of alcohol on folate metabolism
Annu Rev Med
Methylenetetrahydrofolate reductase polymorphism, dietary interactions, and risk of colorectal cancer
Cancer Res
Methylenetetrahydrofolate reductase, alcohol dehydrogenase, diet, and risk of colorectal adenomas
Cancer Epidemiol Biomarkers Prev
A methylenetetrahydrofolate reductase polymorphism and the risk of colorectal cancer
Cancer Res
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Supported by Public Health Service grants CA-41108 and CA-23074, the Specialized Program of Research Excellence in Gastrointestinal Cancer (CA-95060) from the National Cancer Institute, and a Cancer Research and Prevention Foundation grant.