Increased Ultraviolet Radiation Exposure May Protect Against HL, Particularly in Those With EBV-Positive Disease

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Increased exposure to ultraviolet radiation may offer protection against Hodgkin lymphoma (HL), particularly against Epstein-Barr virus (EBV)-positive HL, according to a pooled analysis of studies involving 1,320 HL patients and 6.381 controls. 

“Our pooled analysis of 7,701 participants from 4 independent case control studies of HL found more than a 20% to 30% reduction of risk of HL associated with several measures of [ultraviolet radiation] exposure over the lifespan (ie, inverse associations of childhood and adulthood [ultraviolet radiation] exposure, use of sunlamps, and history of sunburns with HL risk),” investigators from Europe and the United States reported in Blood. “In addition, this analysis provided evidence for a significant inverse exposure-response trend in the association between [ultraviolet radiation] exposure and EBV-positive HL risk in particular.”

Study Background

Ultraviolet radiation exposure “has been associated with HL risk, albeit inconsistently and based on only a few studies,” the authors noted, and these studies did not address the role of ultraviolet radiation in relation to HL heterogeneity. “To address this question, we took advantage of an international collaboration under the auspices of the International Lymphoma Epidemiology Consortium (InterLymph) to achieve sufficient numbers of study subjects for meaningful subgroup analyses. We conducted a collaborative pooled analysis of the role of [ultraviolet radiation] exposure in HL risk focusing on timing and type of exposure and considering epidemiologically distinct disease subtypes defined by age group, histologic subtype, and EBV status of the tumor,” the authors explained. 

The four studies in the pooled analysis “were conducted during the early 2000s in Europe and included HL patients age 16 to 80 years at diagnosis, with no history of hematologic or other neoplasms, immunosuppression for organ transplantation, or HIV infection,” the investigators noted. Almost all patients (99.7%) self-reported their race as white. “In all, 208 tumors (28%) were classified as EBV-positive and 526 tumors as EBV-negative,” the researchers reported.

Investigators estimated lifetime, adulthood, and childhood ultraviolet radiation exposure and history of sunburn and sunlamp use. “We observed statistically significant inverse associations with HL risk for ultraviolet radiation exposures during childhood and adulthood, sunburn history, and sunlamp use, but we found no significant dose-response relationships,” they stated. “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 [ultraviolet radiation] exposure category), with a significant linear trend for overall exposure (P = .03).”

Implications of the Findings

The stronger association between ultraviolet radiation exposure and EBV-positive HL “further support etiologic heterogeneity in HL,” the authors concluded. “Plausible mechanisms involving [ultraviolet radiation] induction of regulatory T cells or the cellular DNA damage response suggest opportunities for new prevention targets.” 

The investigators “leveraged the strengths of a pooled analysis to provide the first investigation of personal history of [ultraviolet radiation] exposure and HL according to disease subtype, taking into account HL histology as well as tumor EBV status,” noted an accompanying editorial by Lindsay M. Morton, PhD, and D. Michal Freedman, JD, MPH, PhD, of the National Cancer Institute, Division of Cancer Epidemiology and Genetics. “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 and should be a priority for future investigation.” 

The editorial also noted that measuring ultraviolet radiation exposure is very complex, and the pooled analysis did not take into account ambient ultraviolet radiation, which can vary substantially by location and modify the impact of personal behaviors. ■

Monnereau A, et al: Blood 122:3492-3499, 2013.
Morton LM, Friedman DM: Blood 122:3395-3397, 2013.