In this issue of Blood, based on a large, prospective cohort study of 121 216 California women, Chang et al report on an inverse association between ultraviolet radiation exposure and a 40% to 50% reduced risk of developing non-Hodgkin lymphoma (NHL)—particularly diffuse large B-cell lymphoma (DLBCL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)—and multiple myeloma.1 

Using the large, prospective California Teachers Study cohort, the authors identified 629 and 119 women who developed NHL (including CLL/SLL) and multiple myeloma after joining the cohort.1  The authors examined the association of prospectively ascertained residential ambient ultraviolet radiation exposure among these patients (cases) in relation to the entire cohort (controls). In their statistical models, they evaluated the observed 40% to 50% reduced risk of developing NHL and multiple myeloma in relation to skin sensitivity to sunlight, race/ethnicity, body mass index, and socioeconomic status. None of these factors modified the observed association between ultraviolet radiation exposure and a decreased risk for lymphoid malignancies.

Interestingly, in their analyses, Chang et al did not find dietary vitamin D to be associated with the risk of developing lymphoma or multiple myeloma. Thus, the results from this large prospective study suggest that regular routine residential ultraviolet exposure may have a protective effect against lymphoma and multiple myeloma; and this may be because of mechanisms that are independent of vitamin D.

As pointed out by Chang et al, a protective effect of exposure to ultraviolet radiation on the risk of NHL has been reported for more than a decade.2-7  Because most prior studies have been retrospective in nature,2-7  one may raise concerns about potential types of bias (eg, recall, selection, and survival bias). However, the current prospective study shows results that are similar to these prior investigations.1 

The new observation in the present study is the lack of an association between vitamin D from diet and the risk of lymphoid malignancies. Chang et al had access to dietary intake data from a food questionnaire, including information total (from food and multivitamins) and dietary (from food only) vitamin D, as well as total and dietary calcium and dietary retinol (because the latter 2 micronutrients are negative regulators of biologically available vitamin D). Total and dietary intake of vitamin D, retinol, and calcium were not associated with risk of NHL or multiple myeloma; the same was true when the analysis was restricted to participants who did not use multivitamins, vitamin A supplements, calcium supplements, dietary vitamin D, retinol, or calcium. In their report, Chang et al discuss strengths and limitations of their study.

Given the observed lack of a role for vitamin D, the association between ultraviolet radiation exposure and a 40% to 50% reduced risk of developing NHL and multiple myeloma remains a mystery. Future molecular studies are needed to clarify the underpinnings of these findings. For example, as mentioned in the article, it is possible that ultraviolet radiation–mediated induction of regulatory T cells may play a role.8 

Conflict-of-interest disclosure: The author declares no competing financial interests. ■

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