Exposure to UV radiation and risk of Hodgkin lymphoma: a pooled analysis

Abstract

• Our pooled analysis found an inverse association between several measures of UVR exposure and Hodgkin lymphoma. • Significant UVR-related inverse associations of EBV-positive HL with a doseresponse relationship support etiologic heterogeneity in HL.Ultraviolet radiation (UVR) exposure has been inversely associated with Hodgkin lymphoma (HL) risk, but only inconsistently, only in a few studies, and without attention to HL heterogeneity. We conducted a pooled analysis of HL risk focusing on type and timing of UVR exposure and on disease subtypes by age, histology, and tumor-cell Epstein-Barr virus (EBV) status. Four case-control studies contributed 1320 HL cases and 6381 controls. We estimated lifetime, adulthood, and childhood UVR exposure and history of sunburn and sunlamp use. We used 2-stage estimation with mixed-effects models and weighted pooled effect estimates by inverse marginal variances. We observed statistically significant inverse associations with HL risk for UVR exposures during childhood and adulthood, sunburn history, and sunlamp use, but we found no significant doseresponse relationships. Risks were significant only for EBV-positive HL (pooled odds ratio, 0.56; 95% confidence interval, 0.35 to 0.91 for the highest overall UVR exposure category), with a significant linear trend for overall exposure (P 5 .03). Pooled relative risk estimates were not heterogeneous across studies. Increased UVR exposure may protect against HL, particularly EBV-positive HL. Plausible mechanisms involving UVR induction of regulatory T cells or the cellular DNA damage response suggest opportunities for new prevention targets. (Blood. 2013;122(20):3492-3499)

Subsequent malignancies among long‐term survivors of Hodgkin lymphoma and non‐Hodgkin lymphoma: a pooled analysis of German cancer registry data (1990–2012)

“…Exposure to ultraviolet radiation (UVR), a known risk factor for melanoma, has also been described as a potential common risk factor for NHL and melanoma (Adami et al , ; Hu et al , ). However, there is no conclusive evidence for an association between UVR exposure and the risk of developing NHL/HL, given that results from several recent studies support a protective effect of UVR exposure on NHL (Armstrong & Kricker, ) and HL risks (Monnereau et al , ). Tobacco smoking could be a potential shared risk factor between HL, NHL and lung cancer, particularly as there is evidence linking cigarette smoking to HL and NHL risks (Morton et al , ; Sergentanis et al , ).…”

A critical review of the epidemiology of Agent Orange or 2,3,7,8-tetrachlorodibenzo-p-dioxin and lymphoid malignancies

“…Cigarette smoking is positively associated with risk of EBV-positive and mixed-cellularity HL [81], and obesity appears to increase HL risk [50], whereas alcohol consumption may be inversely associated [82] and sun exposure may decrease EBV-positive HL risk [83]. Otherwise, few HL risk factors have been confirmed across multiple studies [67e71].…”

Shedding light on UVR and Hodgkin lymphoma

“…Monnereau et al leveraged the strengths of a pooled analysis to provide the first investigation of personal history of UVR exposure and HL according to disease subtype, taking into account HL histology as well as tumor EBV status. 1 Interestingly, the data suggest that the inverse association may be stronger for EBV-positive than EBV-negative tumors. Although the finding requires confirmation, evidence for etiologic heterogeneity within HL has accumulated since the idea was first proposed nearly half a century ago 2 and should be a priority for future investigation.…”

“…Additionally, pooled studies use individual-level data, which, unlike meta-analyses, allow exposure variables in each study to be redefined to a common scale. On the other hand, as Monnereau et al acknowledge, 1 these harmonized variables may in fact obscure variability in exposure definitions arising from differences in the wording and structure of study questionnaires. More importantly, the detailed exposure characterization that may make an individual study so valuable is unlikely to be similar across studies, so the range of exposure variables that can be considered in a pooled analysis is often limited.…”