Diet and epigenetics in colon cancer

Abstract

Over the past few years, evidence has accumulated indicating that apart from genetic alterations, epigenetic alterations, through e.g. aberrant promoter methylation, play a major role in the initiation and progression of colorectal cancer (CRC). Even in the hereditary colon cancer syndromes, in which the susceptibility is inherited dominantly, cancer develops only as the result of the progressive accumulation of genetic and epigenetic alterations. Diet can both prevent and induce colon carcinogenesis, for instance, through epigenetic changes, which regulate the homeostasis of the intestinal mucosa. Food-derived compounds are constantly present in the intestine and may shift cellular balance toward harmful outcomes, such as increased susceptibility to mutations. There is strong evidence that a major component of cancer risk may involve epigenetic changes in normal cells that increase the probability of cancer after genetic mutation. The recognition of epigenetic changes as a driving force in colorectal neoplasia would open new areas of research in disease epidemiology, risk assessment, and treatment, especially in mutation carriers who already have an inherited predisposition to cancer.

Figure 1

Folate, in the form of methyltetrahydrofolate (methyl-THF), is involved in remethylation of homocysteine to methionine, which is a precursor of SAM, the primary methyl group donor for most biological methylation reactions, also in DNA[64]. Folate deficiency may thus enhance CRC through an induction of genomic DNA hypomethylation. Expression of several enzymes (GHMT, MTHFR, BHMT, MAT, SAHH, CBS) involved in methyl metabolism can be regulated by diet such as availability of nutrients including essential amino acids, vitamins B2, B6 and B12, and Zinc (Zn).