Is a personal history of nonmelanoma skin cancer associated with increased or decreased risk of other cancers?

Two conflicting hypotheses have been tested concerning the association between a personal history of nonmelanoma skin cancer (NMSC) and risk of other malignancies. One hypothesis is that as a marker of extensive sunlight exposure and hence vitamin D status, NMSC should be inversely associated with risk of other cancers. Alternatively, under the multiple primary cancer model, NMSC is postulated to be an informative first cancer to study as a marker of increased risk of subsequent primary cancer diagnoses. In this journal issue, Ong and colleagues report the results of a large-scale study in the United Kingdom with findings that NMSC was significantly associated with increased risk of a broad spectrum of other malignancies, with the associations stronger the younger the age of onset of NMSC. These results are consistent with the larger body of evidence on this topic, which is highly asymmetrical in favor of the multiple primary cancer hypothesis. Two divergent hypotheses have been tested, with the empirical evidence unequivocally indicating that NMSC is a marker of a high cancer risk phenotype. Future research is warranted to better characterize this association, to understand why NMSC is a marker of excess risk of other cancers, and to determine whether this association is clinically relevant.