Methyl supply, methyl metabolizing enzymes and colorectal neoplasia.
A low intake of vegetables (but not fruit) is established as a risk factor for colon cancer. Although there are a multitude of active agents that may explain this, one important candidate is folate. Among studies specifically examining intake of folate derived from food and supplements, higher intake is generally associated with lower risk of both adenomas and cancer. Other nutrients associated with the folate pathway-methionine, vitamin B-6, vitamin B-12-or that impact the pathway-alcohol-have also been shown to influence risk in predictable ways. Polymorphisms in enzymes involved in the metabolism of folate also are associated with modification in risk, but essentially only in the presence of low intakes of folate and related nutrients. The consistency of the above evidence suggests that folate is an active agent, not just a marker for the intake of other effectors found in vegetables and multivitamin preparations. There are at least two mechanisms that may explain these findings: folate is central both to the provision of S-adenosylmethionine, the universal methyl donor, and to the provision of nucleotides for DNA synthesis and repair. Fortification of food with folate, as well as intake from multivitamin and pharmacological sources, may increasingly contribute to the primary prevention of colorectal neoplasia although it is possible that there is such a condition as having too much folate.
Potter
John D
JD
Cancer Prevention Research Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA. jpotter@fhcrc.org
D000428:Alcohol Drinking; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000378:metabolism; D011110:Polymorphism, Genetic; D012307:Risk Factors; D014675:Vegetables
D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)