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. Cancer Epidemiol Biomarkers Prev;

Context: Based on empirical evidence, the hypothesis has been set forth that a personal history of non-melanoma skin cancer (NMSC) may be a marker of a high cancer-risk phenotype. Others hypothesize that NMSC may be a marker of high vitamin D synthesis and therefore inversely associated with risk of other malignancies. Objective: To reconcile these divergent views, we carried out a systematic review to determine the overall association between nonmelanoma skin cancer and subsequent risk of other cancers. Data Sources: PubMed and Ovid/MEDLINE databases were searched through March 2009. The formal search was supplemented by hand searches. Study selection: Articles were included if sufficient information was presented to estimate the risk of developing other cancers following NMSC. Data extraction: Articles were reviewed and data abstracted independently in duplicate with disagreements decided by consensus. Results: Of the 21 included articles, 15 presented on NMSC in relation to risk of all other cancers combined. NMSC was associated with a 17% increased future risk of another malignancy (summary random-effects RR (SRR) 1.17, 95% confidence interval (CI) 1.11–1.22). This association held true for both squamous cell carcinoma (SRR 1.21, 95% CI 1.14–1.28) and basal cell carcinoma (SRR 1.15, 95% CI 1.07–1.24), and both men (SRR 1.15, 95% CI 1.09–1.20) and women (SRR 1.10, 95% CI 1.04–1.15). Conclusions: Strong, consistent evidence indicates that a personal history of NMSC is associated with an increased risk of developing other malignancies. For reasons that are presently unknown, nonmelanoma skin cancer may be a marker of a high cancer-risk phenotype. Citation Information: Cancer Prev Res 2010;3(1 Suppl):A34.

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