Among scientists studying genetics and cancer, epigenetics is a prominent buzz word. What is epigenetics? The term was introduced in 1942 as the study of the processes by which genotype (basically the DNA sequence of an organism) gives rise to phenotype (the observable appearance of an organism). In other words, the sequence of the DNA nucleotides (building blocks of DNA) is essentially unchanged as the DNA is duplicated in cell division.
Recently the National Cancer Institute invited applications for grants proposing innovative, preclinical and clinical research to determine how diet and dietary factors impact epigenetic processes involved with cancer prevention. Epigenetic events can result in change of gene expression without involving changes in gene sequence. Thus, an epigenetic event can impact the heritable control of the expression and use of the DNA sequence.
One widely studied epigenetic process is methylation of DNA and has implications in cancer. Normally we think of cancer as being caused by exposure to mutagens resulting in an alteration of the nucleotide sequence of the DNA (this is a non-epigenetic event). If these alterations are not corrected by DNA repair enzymes, normal control of gene expression (turning genes on or off) can be lost resulting in cancer. These changes are then heritable in the cell or tissue where the mutation took place. Many studies have shown that epigenetic events which do not change the sequence of nucleotides but modify the DNA by altering the methylation pattern of the DNA can also be deleterious and result in cancer.
DNA methylation involves transfer of a single carbon from S-adenosylmethionine (also known as SAM or SAM-e) to specific short DNA nucleotide sequences and is catalyzed by one of the DNA methyltransferase enzymes. Research has shown that improper DNA methylation (not enough or too much) can either activate or inactivate a gene. Simply put, if certain genes are activated when they are supposed to be inactive or, vice versa, inactivated when they are supposed to be active, cancer can result.
Recent evidence suggests that diet can be a key regulator of epigenetic DNA methylation. Research at the Grand Forks Human Nutrition Research Center (GFHNRC) and elsewhere has focused on determining how diet influences the metabolism of SAM and how this then affects DNA methylation. The amino acid methionine is used to synthesize SAM. After SAM donates its methyl group (single carbon moiety) it forms S-adenosylhomocysteine (SAH). SAH is then metabolized to homocysteine. The amount of homocysteine present in a tissue or blood is usually low because it is further metabolized with the aid of dietary factors including vitamin B6, vitamin B12, folic acid, methionine, and choline. Laboratory animal studies have shown that a deficiency of one or more of these dietary factors can result in decreased synthesis of SAM and possibly increased synthesis of SAH or homocysteine. Increased amounts of SAH or homocysteine can be harmful. Increased concentrations of homocysteine in blood have been correlated with increased cardiovascular disease and high amounts of SAH are known to inhibit DNA methylation reactions. Thus, deficiencies of the dietary factors including vitamin B6, vitamin B12, folic acid, methionine, and choline can result in aberrant methylation patterns in DNA and could result in cancer if the dietary deficiency is prolonged. It is believed that diet is the single greatest contributor to human cancer, possibly accounting for 35-45% of the disease.
Research at the GFHNRC is attempting to determine the role of epigenetic events, as caused by poor nutrition, in cancer. Cancer is an extremely difficult problem. For health, some of the best advice is to eat a well balanced diet with plenty of whole grains, fruits, and vegetables and to exercise regularly.