Vitamin D, Sun Exposure, and Lymphoma Risk.
Authors: Kelly Jennifer L. , Friedberg Jonathan W. , Calvi Laura M. , van Wijngaarden Edwin , Fisher Susan G. 
Published: April 2020

Abstract
While a large number of exogenous and endogenous factors have been examined, the etiology of most lymphoma subtypes remains largely unknown. However, recent research suggests that sunlight exposure is associated with reduced lymphoma risk. As sunlight is our major source of vitamin D, it has been suggested that increases in serum vitamin D are responsible for this association. Extra-renal activation of vitamin D results in autocrine and paracrine effects including: maintaining regulation of cell cycle proliferation, apoptosis induction, and increased cell differentiation signaling. Animal and human studies investigating the association between vitamin D and other cancers have provided support for a protective effect of vitamin D related to malignancy. We conducted a case-control study in western New York State to test the hypothesis that a history of vitamin D insufficiency increases the risk of lymphoma. Between October 2005 and September 2007, we recruited 140 newly diagnosed and previously untreated lymphoma cases and 139 clinic-based controls. Cases and controls were recruited concurrently to account for seasonal variation in vitamin D, and a serum sample and self-administered survey were collected from each subject. Current serum 25(OH)D levels were measured by radioimmunoassay (Heartland Assays Inc., Ames, IA). We used multiple linear regression to obtain quantitative estimates of past (5–10 years ago) serum vitamin D concentrations based on survey data and measured current vitamin D levels. Subsequently, we evaluated the association between estimated past vitamin D insufficiency (25(OH)D &lt; 30 ng/mL) and lymphoma risk with multiple logistic regression, controlling for the effects of age, gender, race, prior skin cancer diagnosis, known family history of lymphoma or other cancer, alcohol use, and BMI. Additionally, we examined the association between self-reported past sun exposure and lymphoma risk. The case population included 89 males (64%), 124 whites (89%), and median age was 60; the control population included 61 males (44%), 123 whites (88%), and median age was 52. Median time between case diagnosis and study participation was 21 days (5 month maximum). Cases presented predominantly with advanced stage (64% Stage III/IV) diffuse large B cell lymphoma (23%) and follicular lymphoma (32%) subtypes, and 30 (21%) cases had documented B symptoms. While serum vitamin D values ranged from 2.5 to 45.6 ng/mL, we were surprised to find that the majority of the study population (74%) was vitamin D insufficient. Those with past vitamin D insufficiency were found to have a slightly lower lymphoma risk (multivariate adjusted odds ratio (OR) = 0.68; 95% confidence interval (CI) = 0.38 – 1.23), but this result was not statistically significant. Self-reported past sunbathing (OR=0.30, 95% CI: 0.11–0.85) and past outdoor occupation (OR=0.49, 95% CI: 0.25–0.96) were statistically significantly associated with reduced lymphoma risk. This study fails to provide evidence to support an important role of vitamin D insufficiency in lymphoma etiology. However, we confirmed the previously reported decrease in lymphoma risk associated with measures of increased sun exposure, thereby supporting the validity of our study data. Moreover, our findings suggest that vitamin D insufficiency may not explain the observed association between sun and lymphoma. In light of both the high prevalence of vitamin D insufficiency and the known risk of excessive chronic sun exposure, further investigation of the risks of vitamin D insufficiency, as well as alternative pathways for the demonstrated inverse associations between sun exposure and lymphoma risk, is warranted.