Nonmelanoma skin cancer and the risk of second primary cancers: a systematic review.

BACKGROUND Based on empirical evidence, a personal history of nonmelanoma skin cancer (NMSC) has been hypothesized to be a risk factor for other cancers. Others hypothesize that NMSC may be a marker of high cutaneous vitamin D synthesis and therefore inversely associated with risk of other malignancies. To reconcile these divergent views, we carried out a systematic review to determine the association between NMSC and subsequent risk of other cancers. METHODS Bibliographic databases were searched through March 2009. Studies were included if sufficient information was presented to estimate the risk of developing other cancers following NMSC. Studies were reviewed and data were abstracted independently in duplicate with disagreements resolved by consensus. RESULTS Of the 21 included studies, 15 reported the association between NMSC and risk of all other cancers combined. NMSC was significantly associated with increased risk of another malignancy among cohort studies based on cancer registries summary random-effects relative risk (SRR), 1.12; 95% confidence interval (CI), 1.07-1.17; n = 12 studies) and those with individual-level data (SRR, 1.49; 95% CI, 1.12-1.98; n = 3). In stratified analyses of registry studies, this association held true for both squamous (SRR, 1.17; 95% CI, 1.12-1.23; n = 7) and basal cell carcinoma (SRR, 1.09; 95% CI, 1.01-1.17; n = 7), and both men (SRR, 1.14; 95% CI, 1.09-1.20; n = 12) and women (SRR, 1.10; 95% CI, 1.04-1.15; n = 12). CONCLUSIONS Strong, consistent evidence indicates that a personal history of NMSC is associated with increased risk of developing other malignancies. IMPACT For unknown reasons, NMSC may be a risk factor for other cancers.