Frontiers in Cancer Epidemiology: A Challenge to the Research Community from the Epidemiology and Genomics Research Program at the National Cancer Institute

In recognition of the 20th year of publication of CEBP, the editor (1) proposed a series of invited commentaries from experts in various disciplines to reflect on major advances and trends in cancer epidemiology over the last two decades and to foresee “what lies ahead.” Pieces published in response to this call and some related initiatives have challenged the epidemiology community to extend its boundaries and look to the future. A recent commentary in CEBP entitled “bigger, better, sooner: scaling up for success” (2) emphasized the importance and challenges confronting collaborative multidisciplinary research.

The Epidemiology and Genomics Research Program (EGRP) at the National Cancer Institute (NCI; ref. 3) has initiated a strategic planning effort to develop scientific priorities for cancer epidemiology research in the next decade, during a period of great scientific advances and resource constraints. EGRP would like to engage the research community and other stakeholders in a planning effort that will include a workshop in December 2012 to help shape new foci for cancer epidemiology research. To facilitate the process of defining the future of cancer epidemiology, we invite the research community to join in an ongoing web-based conversation at http://blog-epi.grants.cancer.gov/ to develop priorities and the next generation of high-impact studies.

EGRP is the largest funder of cancer epidemiology grants in the world. Figure 1 shows trends in the numbers of grants funded in the past decade. During this period, a rapid growth occurred in epidemiologic research on genetic and environmental determinants of cancer occurrence and outcomes. Large-scale epidemiologic studies have been instrumental in assessing risk factors for almost all cancer types, cancer precursors, and response to interventions, as well as survivorship and outcomes. EGRP also focuses on nurturing interdisciplinary consortia (4) that can answer unique questions in cancer occurrence and outcomes by pooling data across a large number of institutions from around the world and facilitating the translation of these findings to clinical and public health applications. In addition, consortia of existing cohort studies have been used to examine risk factors for cancer occurrence and outcomes, common diseases other than cancers, as well as the relationships between cancer and non-cancer health outcomes in diverse populations (5). The growth in cancer epidemiology research has been driven by advances in genomics and related fields and the emergence of genome-wide association studies (GWAS) that have identified an unprecedented number of genetic variants associated with cancer risk (6).

Cancer epidemiology has resulted in many success stories that have led to improved policy and practice (7). These include, among others, the unraveling of cigarette smoking as a cause of lung and many different types of cancer, the role of human papilloma virus (HPV) in cervical and other cancers, and the discovery of hundreds of genetic loci as risk factors for various types of cancer. Despite these successes, observational epidemiology has methodologic limitations that affect the ability to infer causation. To overcome limitations that have perhaps hindered the progress and evolution of epidemiologic studies, we need to identify new approaches and apply lessons learned from other fields. Our aim should be to enhance the application of epidemiologic methods along the translational continuum from basic discoveries to population health impact (8).

More than 10 years into the 21st century, we are at a major crossroads in our understanding of cancer. Tools of molecular biology, genomics, and other high-throughput “omic” technologies are increasingly integrated into epidemiologic investigations. In a 2011 NCI Town Hall Meeting, Dr. Harold Varmus, Director of the NCI, said “I expect to see a pretty dramatic revolution in epidemiology… …defining cancers by genetic subsets. I expect to see molecular tools brought more forcefully into the realm of cancer diagnosis… talking about ways to discriminate among early lesions and pre-cancerous lesions that may have malignant potential” (9). Along with the emerging tools of genomics come refined social, behavioral, and environmental measurements at the individual, community, and health system levels and the ability to assess gene–gene and gene–environment interactions. There is an increased focus on complex “systems” approaches in understanding the occurrence of cancer and intervening at multiple levels (10). All of this research has been supported by tremendous advances in bioinformatics and information technology (11, 12), allowing us to collect, analyze, and synthesize information from multiple disciplines at an ever-increasing pace. With these opportunities, however, come the major challenge of dealing with the data deluge and uncovering true causal relationships from the millions and millions of observations that are background noise. Thus, in funding cancer epidemiology studies, we now confront important challenges and must make choices of scientific direction to maximize the use of existing research infrastructures and plan wisely for new ones, as we respond to changing resources.

The process of defining the future of epidemiology is not only occurring in cancer but also in other fields. In a recent commentary published in the American Journal of Epidemiology (13), leaders of the epidemiology program at the National Heart, Lung and Blood Institute (NHLBI) have also reflected on the critical questions that confront the cardiovascular epidemiology community in the next decade in the face of constrained resources. NHLBI has invited the community to provide answers to 4 critical questions using their digital forum at http://nhlbiepi.wordpress.com/. How can we avoid wasting resources on studies that provide little or incremental knowledge? How can we assure that we direct our resources as economically as possible toward innovative science? How can we be nimble and responsive to new opportunities? How can we identify prospectively the most meritorious research questions? (13). Obviously, the same questions apply to the future of cancer epidemiology.

EGRP invites the research community to contribute their perspectives on the major questions that cancer epidemiology should address in the next decade to make an impact on public health. In addition, we are interested in input on (i) methods and technologies that should be integrated in cancer epidemiology; (ii) construction, maintenance, and optimization of representative cohorts needed to study determinants of the transition from health to cancer and related outcomes, (iii) use of epidemiology to inform and complement treatment and prevention randomized clinical trials for filling evidentiary gaps, and (iv) epidemiologic approaches, including the use of networks of consortia, for ongoing integration of knowledge emerging from basic, clinical, and population sciences. For more information on the “Cancer Epidemiology Matters Blog,” and how you can contribute to the ongoing online dialog, please visit http://blog-epi.grants.cancer.gov/

No potential conflicts of interest were disclosed.

Conception and design: M.J. Khoury, D.S. Seminara, C.E. Harvey

Development of methodology: M.J. Khoury, A. N. Freedman

Acquisition of data (provided animals, acquired and managed patients, provided facilities, etc.): M.J. Khoury, D.S. Seminara

Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis): M.J. Khoury, D.S. Seminara, A.N. Freedman, E.M. Gillanders

Writing, review, and/or revision of the manuscript: M.J. Khoury, A.N. Freedman, E.M. Gillanders, C.E. Harvey, C. Kaefer, B.C. Reid, S. Rogers, D.S. Seminara

Administrative, technical, or material support (i.e., reporting or organizing data, constructing databases): M.J. Khoury