Various forms of
immunotherapy utilizing bacille Calmette-Guérin
vaccine or
vaccinia vaccine have been evaluated in clinical trials on
melanoma patients. The effect of the "natural" application of these vaccinations, administered to provide protection against
tuberculosis and
smallpox, has, however, never been studied in epidemiologic investigations on risk factors for
melanoma. In a case-control study comprising 11 institutions in seven countries we recruited 603 incident
melanoma cases and 627 population controls frequency matched to the cases with respect to sex, age, and ethnic origin within each center to assess this relationship to obtain insights into the prevention of
melanoma. Exposure information, incorporating also detailed ascertainment of potential confounding variables, was obtained in standardized personal interviews at the study subject's home. We found an inverse association between
melanoma risk and previous bacille Calmette-Guérin
vaccine/vaccinia vaccination depicted by an adjusted odds ratio of 0.44 (95% confidence interval: 0.26-0.72) for those vaccinated against
tuberculosis and
smallpox compared with subjects without a positive history of either vaccination. A variety of subgroup analyses showing a consistent pattern of results make it unlikely that the observed inverse association is a spurious finding. We conclude that bacille Calmette-Guérin vaccination and
vaccinia vaccination may lower
melanoma risk. Current immunologic theory of
melanoma development provides a sound basis for understanding the
biologic plausibility of the findings that have to be confirmed in future studies.