Case-control design as investigative approach to assessing cancer etiology: development and future perspectives

The case-control method evolved out of analyses of series of cases. The analytic form of the case-control study can be found in the 19th century medical literature, but did not appear to be viewed as a special or distinct methodology. The first modern case-control study was the Janet Lane-Claypon's study of breast cancer in 1926, but the design was used only sporadically in medicine until 1950, when 4 published casecontrol studies linked smoking and lung cancer. These 1950s studies synthesized the essential elements of the case-control comparison, produced a conceptual shift within epidemiology, and laid the foundation for the rapid development of the case-control design in the subsequent half century. The powerful consistency of these case-control studies, and the replication of their findings in later prospective studies, promoted the general acceptance of the case-control study as a scientific tool in clinical research. Newer case-control studies have benefited from the advances in design, execution and analysis since 1950s. These advances include more rigorous selection and matching of case and control population, improved interviewing techniques, location of the design within a general framework of epidemiologic strategies for relating exposure to disease, understanding of the measures of effect, and application of increasingly sophisticated statistical procedures to findings. This review traces the development and future perspectives of the case-control design to assessing cancer etiology. With illustrations drawn primarily from the literature on its use and the value of its results to unravelling the etiology of malignant diseases, we tried to explore if the case-control approach firmly ensconced in epidemiology as investigational tool and rivals in importance the more straightforward cohort approach.