Vitamin D and Nonmelanoma Skin Cancer in a Health Maintenance Organization Cohort

Objective: To examine the association of serum 25-hydroxyvitamin D (25-OHD) with the risk of nonmelanoma skin cancer (NMSC), defined as squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). Design: Cohort study. Setting: Health maintenance organization. Patients: The study included 3223 white health maintenance organization patients who sought osteoporosisor low-bone-density-related advice from 1997 to 2001. Interventions: Vitamin D levels were ascertained at the time of the initial appointment, and a sufficient vitamin D level was defined as a baseline serum 25-OHD level greater than or equal to 30 ng/mL (to convert to nanomoles per liter, multiply by 2.496) and as a deficient vitamin D level less than 15 ng/mL. Main Outcome Measures: The NMSC cases diagnosed between 1997 and 2009 were ascertained using claims data, considering first occurrence of specified disease outcome and complete person-years of follow-up since baseline. Charts were abstracted for histologic subtype and anatomical location. Results: More patients were vitamin D insufficient (n = 2257) than sufficient (n = 966). There were 240 pa-with NMSC: 49 had an SCC, 163 had a BCC, and 28 had both. Vitamin D levels greater than 15 ng/mL ( not deficient level) were positively associated with NMSC (unadjusted odds ratio [OR], 1.7; 95% confidence interval [CI], 1.04-2.7), and this association was sustained after additional risk factors were adjusted for (adjusted OR, 1.8; 95% CI, 1.1-2.9). The 25-OHD levels were similarly positively associated, though statistically insignificant, with NMSC occurring on less UV-exposed anatomical locations (adjusted OR, 2.2; 95% CI, 0.7-7.0), whether for SCC (adjusted OR, 3.2; 95% CI, 0.4-24.0) or for BCC, although the risk estimate for BCC was lower (adjusted OR, 1.7; 95% CI, 0.5-5.8). Conclusions: An increased baseline serum 25-OHD level was significantly associated with an increased NMSC risk. This association was positive, though nonsignificant on less UV-exposed body sites, and UV exposure remains a likely confounder. The complex and confounded relationship of vitamin D, UV, and NMSC makes classic epidemiological investigation difficult in the absence of carefully measured history of cumulative UV exposure.