Diet, SNPs and Cancer
What is the relationship between diet and SNPs, and how might this relationship influence cancer risk? Although this area of research is in its infancy, some relevant data from investigations of other diseases provides a hint that SNPs may link dietary intake of certain nutrients to disease risk, including risk for cancer.
One good example of research that is helping to establish the link between nutrition, SNPs and cancer is the study of how the B-vitamin folic acid acts to prevent neural-tube defects (NTDs). Consumption of adequate folic acid is known to prevent the occurrence and recurrence of NTDs, but the mechanism is not clear. The enzyme protein named methylenetetrahydrofolate reductase (abbreviated MTHFR) is required for proper metabolism of folic acid. An SNP in MTHFR was identified several years ago, and this SNP resulted in lower activity of MTHFR. This SNP has been associated with increased risk for NTDs in many (but not all) investigations. A recent study found that a combination of poor folic acid status (low folic acid levels in blood cells) and the SNP was associated with a greater risk for NTDs than either variable alone. These results suggest that the SNP defect was exacerbated by poor folic acid levels in the blood, and that increased intake of this vitamin might overcome the genetic defect that results in increased NTDs.
This same MTHFR SNP has recently been associated with several types of cancer. In a series of studies conducted at Harvard University, the MTHFR polymorphism was found to actually reduce colon cancer risk in men, but this protection due to the SNP was absent in subjects who were folic acid deficient. The protective effect of the SNP also disappeared in men who consumed more than one drink of alcohol per day. The authors explained that alcohol acts as a folic acid antagonist and can mimic the effect of folic acid deficiency.
A number of other cancer-related polymorphisms that affect single (SNPs) or multiple nucleotides have recently been described, and the genetic defect caused by the polymorphism may, in many cases, be influenced by alterations in the diet. In some cases, rather than increasing the intake of a potentially beneficial nutrient to overcome the polymorphism, it appears that decreased consumption of a possibly harmful nutrient may be in order. For example, polymorphisms in two enzymes involved in detoxification of carcinogens present in meat have been found to be associated with increased risk of colon cancer in persons who consume red meat. Likewise, a polymorphism in alcohol dehydrogenase, an enzyme involved in alcohol detoxification, has been associated with increased cancer of the oral cavity. These studies suggest that individuals with the former polymorphism should avoid red meat, and those with the latter should avoid alcohol. Information on SNPs will therefore very likely be useful in deciding which nutritional supplements should be taken in increasing amounts, as well as in deciding which nutrients should be avoided.
In the next decade, it is likely that SNPs will enable physicians and other health care professionals to develop tailor-made dietary recommendations based on “SNP profiles” of individual patients. As SNP data accumulates over the next few years, proteins will be identified that have decreased activity as a result of SNPs. There is also the possibility that an SNP could lead to a genetic change that provides its protein product with a selective increase in activity. Proteins that respond to nutrients are already known, and more information on the effect of nutrition on protein expression will be forthcoming in the near future. Once this information becomes available, it is possible that a patient will be screened for SNPs. SNPs whose protein product might prevent cancer will be identified, such as the antioxidant enzymes glutathione peroxidase and superoxide dismutase, or possibly tumor suppressor genes. If it is likely that dietary components (in this example, antioxidant vitamins) might bolster the activity of the protein whose activity was moderately diminished by the SNP, then the physician could recommend a selective increase in the intake of the relevant nutrient.
Of course there will be privacy concerns in this “brave new world.” Will your insurance company or employer (or even a prospective mate) have access to your “SNP profile?” Although this is the topic of another essay, these anxieties will offset the potential benefits of SNPs in preventing cancer and other diseases.
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