Epigenetics is emerging as an important field in cancer epidemiology that promises to provide insights into gene regulation, and facilitate cancer control throughout the cancer care continuum. Increasingly, investigators are incorporating epigenetic analysis into the studies of etiology and outcomes. To understand current progress and trends in the inclusion of epigenetics in cancer epidemiology, evaluation of the published literature and the National Cancer Institute (NCI) supported research grant awards in this field to identify trends in epigenetics research was conducted. Here a summary of the epidemiological studies in NCI’s grant portfolio (from January 2005 through December 2012) and in the scientific literature published during the same period, irrespective of support from NCI is presented.
Methods
NCI supported RPGs related to epigenetic epidemiology funded from January 01, 2005 to December 31, 2012 were included in the portfolio analysis. The portfolio was analyzed using NCI’s Portfolio Management Application software version 13.4. The criteria for inclusion of a project in the analysis were as follows: a) the focus of the project is cancer, b) study involves human subjects, c) focus of at least one of the specific aims in the project is cancer epigenetics, and d) has at least 100 cases and 100 controls. The initial analysis identified 84 RPGs. A manual analysis applying the above criteria eliminated 21 RPGs leaving 63 for further analysis. We searched published literature on epigenetic epidemiology in PubMed from January 1, 2005 to December 31, 2012 using the following search criteria: (epigenesis, genetic[mh] OR epigenomics[mh] OR “DNA methylation” OR methylation[ti] OR “histone modification” OR CIMP[tiab] OR microRNAs[mh] OR “CpG Islands/genetics”[mh] OR methylation[ti]) AND neoplasms[mh] AND (epidemiologic studies[mh] OR risk[mh] OR “population-based”[tiab] OR “odds ratio”[tiab] OR hazard[tiab] OR cohort*[tiab]) AND Humans[Mesh]. The PubMed was also searched from January 1, 2005 to February 02, 2012 using the following MeSH terms and a strategy for non-MEDLINE publications: ((epigen* OR methylation OR histone* OR “CpG islands” OR CIMP OR microRNA* OR miRNA*) AND (cancer[tiab] OR cancers[tiab] OR leukemia*[tiab] OR lymphoma*[tiab] OR melanoma*) AND (“case-control” OR cohort OR trial)) NOT (medline[sb] OR meta-analysis[tiab]). The following elimination criteria were applied: a) studies with less than 100 cancer cases; b) studies published before 2005; c) experimental studies in animals; d) review articles and articles reporting meta-analyses; e) letters, commentaries, editorials and news articles; and f) studies that are not clearly epidemiological. This search yielded 335 publications that are relevant for analysis. As with the grant analysis outlined above, authors listed above coded the publications on study design, organ site, biospecimen type used, exposure evaluated (if applicable), and method/technology used for epigenetic analysis.
Results
The NCI supported grant portfolio analysis indicated that in the field of epigenetics, breast cancer was the most frequently studied cancer type. Blood cells and tumor tissue were the most commonly used biospecimens in these studies, although buccal cells, cervical cells, sputum, and stool samples also were used. DNA methylation profiling was the focus of the majority of studies, but several studies also measured microRNA profiles. Colorectal cancer is the field which was used not only in epidemiologic studies but for molecular classification of the disease also. The current status of epidemiologic studies that are evaluating epigenetic changes in large populations will be presented. Some research needs include developing improved strategies for epigenetic data analysis and interpretation; determining the stability of epigenetic marks in repeated biospecimen samples from the same people over time; and studies that examine the relationship between epigenetic marks in germline DNA and tumor DNA. While there are limitations to the broad application of epigenomics to epidemiology research, there are situations where this type of research is appropriate and it should be considered.