In 1971, cancer epidemiology played an important, if underappreciated, role in NCI research. Studies rarely involved more than a few hundred participants, and were largely directed at how patterns of cancer risk in specific populations were affected by environmental and lifestyle factors.

Today, the molecular epidemiologist has a variety of tools, technologies, and opportunities. NCI has played a significant role in this story, designing important studies of familial cancer and providing ongoing support and direction for a national program in epidemiological research.

"The advent of major advances in molecular science and technology offers the epidemiologist a chance to overcome some weaknesses of the classical approaches of the past," said Dr. Robert N. Hoover, director of the Biostatistics and Epidemiology Program in NCI's Division of Cancer Epidemiology and Genetics (DCEG). This includes better measurement of exposures and outcomes, detection of susceptible subgroups, and insights into the biological mechanisms of disease.

A clear example of this process is the discovery that infection due to the human papillomavirus is responsible for most cases of cervical cancer. By learning about the etiology and epidemiology of this disease, basic researchers in NCI's CCR were able to develop a vaccine that was licensed for clinical use this year.

To maximize the value of powerful new genomic tools, epidemiologists are taking a "more transdisciplinary team-based approach, which NCI is actively promoting through a number of strategic partnerships," said Dr. Joseph F. Fraumeni, Jr., DCEG director.

One such partnership is the Consortium of Cohorts, an international collaboration of intramural and extramural investigators managing 23 independently funded population cohorts that encompass 1.2 million individuals who have provided biospecimens including germline DNA. As cancers arise among these people, nested case-control studies should help evaluate molecular and biochemical biomarkers of susceptibility and early-stage disease.

In another initiative, Dr. Hoover, Dr. Gilles Thomas, and CCR's Dr. Stephen Chanock, who directs the NCI Core Genotyping Facility, are co-leading the Cancer Genetic Markers of Susceptibility (CGEMS) project, along with Dr. David Hunter of the Harvard School of Public Health, to identify genetic alterations that make people susceptible to breast and prostate cancers. Here, too, nested case-control studies will be based on large, ongoing population cohort studies.

You can find more information about how the National Cancer Act has advanced cancer research at http://www.cancer.gov/ aboutnci/nca.

Since one of the limitations of genetic epidemiology in the past was testing for a specific, suspected risk factor, CGEMS represents an evolving model that will transform the approach and power of epidemiology. "Now we can look at nearly all regions of the genome for common genetic variants," said Dr. Chanock. "We're sure to uncover associations with cancer that will surprise us, and unraveling the science behind them is likely to have clinical payoffs because epidemiology is based on actual disease patterns in human populations."