Introduction: Seasonal variations in incidence and mortality after a Hodgkin lymphoma (HL) diagnosis have been previously described with partly conflicting results. The goal of this study is to comprehensively analyze seasonal variation in incidence and mortality risk of HL with a focus on geographic differences. Methods: HL cases diagnosed between 1973 and 2012 in the 18 Surveillance, Epidemiology, and End Results (SEER) registries were eligible (n=50,179). Cases with missing data for at least one of the analyzed variables (n=8,700) and from the two SEER registries “Alaska natives” (n=17) and “Rural Georgia” (n=57) were excluded, leaving 41,405 cases for the study. Seasonality of incidence was analyzed using cosinor analysis. The risk of overall mortality within 3 years following a HL diagnosis in winter (Sep.-Feb.) vs. summer (Mar.-Aug.) was analyzed by employing a Cox proportional-hazards model with correction for known risk factors. Results: HL shows a seasonal incidence pattern with a peak in March and a trough in September (p<0.001). In predefined subgroup analyses, cases of the mixed cellularity (p<0.001), nodular sclerosis (p<0.001) and lymphocyte depleted subtype (p=0.002) showed a seasonal incidence pattern. Seasonality was particularly pronounced in the age groups 20-29, 30-39 and 60-69, coinciding with age groups of increased HL incidence. Cases from lower (<38.05°N) latitudes showed a decreased seasonality of incidence (amplitude=0.055) compared to cases from higher (≥38.05°N) latitudes (amplitude=0.102) (p(diff.)=0.023). The risk of dying in winter vs. summer is increased at higher latitudes (HR: 1.082[1.009;1.161], p=0.027), whereas no seasonal difference in mortality was observed for cases from lower latitudes (HR: 0.990[0.926;1.059], p=0.772). A multiplicative interaction term showed interaction between the latitude and a diagnosis in winter on mortality risk (HR(interaction): 1.119[1.009;1.241], p=0.033). Conclusions: HL exhibits a seasonal incidence and mortality pattern in this most comprehensive analysis performed to date. The seasonal effect on incidence is exacerbated at and the effect on mortality restricted to higher latitudes. As latitude is closely linked to seasonal variations in Vitamin D serum levels, a protective effect of Vitamin D in HL is a possible explanation. Evidence on the direct association between Vitamin D levels and the clinical course of HL should be collected to improve the understanding of Vitamin D in HL.
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