Abstract Background: Results from several recent case-control studies suggest that increased sun exposure may reduce risk of non-Hodgkin lymphoma (NHL). Vitamin D synthesis is hypothesized as one possible mechanism, since solar ultraviolet-B (UV-B) radiation exposure triggers endogenous vitamin D production in the skin. To date, no prospective studies of UV and NHL have been conducted. Methods: We identified 1057 incident cases of NHL through 2006 in the Nurses’ Health Study (NHS), a cohort study of approximately 121,700 women who have been followed since 1976. Ambient UV radiation exposure, as measured by average annual UV-B flux (in R-B counts x 10-4), was estimated for all participants based on residence at various times during life and categorized as 113. Vitamin D intake from food and supplements was calculated based on responses to food frequency questionnaires with follow-up beginning in 1980. Using plasma 25-hydroxyvitamin D (25(OH)D) measurements available for a subset of the NHS population, we developed a linear regression model to predict plasma 25(OH)D levels for the entire cohort based on multiple determinants of vitamin D status, including dietary intake and UV-B flux. Cox proportional hazards models were used to estimate incidence rate ratios (RRs) and 95% confidence intervals (CIs). The main analyses included all cases of NHL; we also performed separate analyses for the most common NHL subtypes [i.e., chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B-cell lymphoma (DLBCL), and follicular lymphoma (FL)]. Results: For most measures of ambient UV-B flux, the risk of NHL was increased for women in the highest category of exposure (i.e., > 113) compared to the lowest (i.e., 113 ranged from 1.10 (95% CI: 0.94, 1.29) for UV-B flux based on residence in 1976 to 1.21 (95% CI: 1.00, 1.47) for UV-B flux at age 15. Positive linear trends were observed for all measures. We observed stronger associations for CLL/SLL than for FL and no association for DLBCL with most measures of UV-B flux. The RR for the highest quintile of total vitamin D intake versus the lowest, after adjusting for age, body mass index, smoking, height, multivitamin use, and intake of retinol, calcium, and total calories, was 1.02 (95% CI: 0.71, 1.46). There was no association between predicted 25(OH)D score and risk of NHL. There did not appear to be differences in effect estimates for vitamin D intake by NHL subtype. Conclusions: Our findings of weak but statistically significant positive associations between UV-B flux assessed at various time points and risk of NHL in this prospective cohort study do not support the hypothesis of a protective effect of sunlight exposure. We found no association between vitamin D intake and risk of NHL, suggesting that if UV exposure is ultimately found to reduce the risk of this cancer, the effect may not act through vitamin D. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2820.
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