Genetic Variation and Cancer: Improving the Environment for Publication of Association Studies

The completion of a working draft of the human genome and the rapidly expanding knowledge base that has accompanied it are having a major impact on our understanding of the role of genes in human cancer. A large number of studies have appeared in the literature that report associations of low penetrance genetic variants with disease or disease-related phenotypes. It is likely that the majority of these variants act in concert with specific environmental exposures, which are often ignored, poorly measured, or not considered at all in genetic association studies. Similarly, it is likely that these genes do not act alone but interact with other genes or biomarkers in identifiable pathways. Therefore, genetic association studies may not result in clear inferences about the causative role of these genes with disease end points and are not always replicated in subsequent studies. Accordingly, a major need in molecular epidemiology is to promote research that identifies biologically plausible, replicable genotype-disease associations.As a forum in which many molecular epidemiologic association studies are reported, Cancer Epidemiology, Biomarkers & Prevention will increasingly prioritize the publication of reports that are more likely to represent disease-causing events. To help in this process, editors and reviewers for Cancer Epidemiology, Biomarkers & Prevention are now being asked to evaluate genetic association papers using stringent criteria. These criteria include the following:The criteria outlined here may be used to prioritize papers for publication, but these criteria specifically do not refer to strength of association. These criteria may apply whether the report is positive or null (see also specific instructions for the Null Reports in Brief section of this journal). Although it is not necessary to incorporate all of the above criteria in every paper reporting genetic associations, close consideration of these criteria by authors, reviewers, and editors should limit the publication of false-positive and false-negative reports. These criteria will be the guide for determining publication priorities in Cancer Epidemiology, Biomarkers & Prevention. The ability to implement these and other measures will allow genetic association studies to provide more meaningful information about disease etiology or outcome and thus allow this information to be further translated into cancer prevention, public health recommendations, clinical practice, or basic science studies that elucidate disease mechanisms. We look forward to responses from readers and reviewers on these guidelines and always welcome other suggestions regarding the quality of the journal.