False-positive results in cancer epidemiology: a plea for epistemological modesty

Abstract

False-positive results are inherent in the scientific process of testing hypotheses concerning the determinants of cancer and other human illnesses. Although much of what is known about the etiology of human cancers has arisen from well-conducted epidemiological studies, epidemiology has been increasingly criticized for producing findings that are often sensationalized in the media and fail to be upheld in subsequent studies. Herein we describe examples from cancer epidemiology of likely false-positive findings and discuss conditions under which such results may occur. We suggest general guidelines or principles, including the endorsement of editorial policies requiring the prominent listing of study caveats, which may help reduce the reporting of misleading results. Increased epistemological humility regarding findings in epidemiology would go a long way to diminishing the detrimental effects of false-positive results on the allocation of limited research resources, on the advancement of knowledge of the causes and prevention of cancer, and on the scientific reputation of epidemiology and would help to prevent oversimplified interpretations of results by the media and the public.

Figure 1

Cumulative meta-analysis of cohort studies of breast cancer and serum level of 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (highest vs lowest category in each study). Estimated relative risks (RRs) are shown with 95% confidence intervals (CIs) (error bars) by year of publication of subsequent reports. In parentheses are references of studies included in the cumulative meta-analyses (see Table 1 for details). Upper confidence limit for the initial RR was 13.5.

Figure 2

Cumulative meta-analysis of cohort studies of lung cancer and occupational exposure to acrylonitrile. Estimated relative risks (RRs) are shown with 95% confidence intervals (CIs) (error bars) by year of publication of subsequent reports. In parentheses are references of studies included in the cumulative meta-analyses (see Table 2 for details).

Figure 3

Funnel plot of results of studies on dioxin exposure and risk of non-Hodgkin lymphoma. Closed diamonds, cohort studies; empty diamonds, case–control studies. RR = relative risk. se = standard error. See (76) for detailed results.