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 osteoporosis- or 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 patients 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.