Diet as a Determinant of DNA Methylation: Potential Role in Cancer Disparities among Populations
Dr. Beverly D. Lyn-Cook, Sr. Research Biologist, FDA-NCTR, Div. of Personalized Nutrition & Med., Jefferson, AR
Dietary factors are becoming increasing important determinants in understanding the molecular mechanisms involved in the etiology of cancer development. The persistent disparities that exist among different ethnic groups, in relation to cancer death rates, warrants expanding research efforts in the role of nutrigenomics in cancer disparities. Ethnic group differences in critical dietary factors intake, in addition to other life-style or environmental factors, may play an important role in cancer biology. DNA methylation, an epigenetic process that affects heritable changes in gene expression without a change in DNA sequence, is now known to be modulated by dietary factors. Dietary factors may exert their effects in carcinogenesis through global hypomethylation, site-specific hypermethylation or histone modification. Earlier studies showed a mechanistic relationship between the lack of key nutrients and activation of oncogenes known to be involved in cancer development (Carcinogenesis 10:1869,1992). These studies led to numerous other studies showing the importance of DNA methylation and cancer. Our laboratory demonstrated in earlier studies, for the first time, a relationship between caloric intake and DNA methylation (Mutation Research, 295(4-6):281-289, 1993). The studies showed that obese animals, which were allowed to eat ad libitum, showed hypomethylated DNA and cells from these animals in culture had a high transforming rate compared to their restricted counterpart. Obesity is now considered a co-morbidity in the development of some cancers. Obesity is increasing in some populations and should be investigated further in playing a role in disparites in cancer deaths. We have further shown in earlier studies that components found in soy can affect methylation profile of specific oncogenes. Research is critically needed in understanding how various bioactive components found in food may have adverse or beneficial effects in individuals. A number of cancers have shown increased expression of DNA methyltransferases 1, 3a and 3b that may play critical roles in downregulating critical suppressor genes through hypermethylation. Recently we have targeted DNA methyltransferases as potential chemoprevention agents in pancreatic cancer. The importance of dietary factors as a determinant of DNA methylation will be discussed in relation to the potential role of critical nutrients in cancer disparities among populations.