Early life sun exposure, vitamin D-related gene variants, and risk of non-Hodgkin lymphoma

Jennifer L. Kelly, Matthew T. Drake, Zachary S. Fredericksen, Yan W. Asmann, Mark Liebow, Tait D. Shanafelt, Andrew L. Feldman, Stephen M. Ansell, William R. Macon, Megan M. Herr, Alice H. Wang, Grzegorz S. Nowakowski, Timothy G. Call, Thomas M. Habermann, Susan L. Slager, Thomas E. Witzig, James R. Cerhan

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27 Scopus citations

Abstract

Purpose: It has been hypothesized that vitamin D mediates the inverse relationship between sun exposure and non-Hodgkin lymphoma (NHL) risk reported in several recent studies. We evaluated the association of self-reported sun exposure at ages <13, 13-21, 22-40, and 41+ years and 19 single nucleotide polymorphisms (SNPs) from 4 candidate genes relevant to vitamin D metabolism (RXR, VDR , CYP24A1, CYP27B1) with NHL risk. Methods: This analysis included 1,009 newly diagnosed NHL cases and 1,233 frequency-matched controls from an ongoing clinic-based study. Odds ratios (OR), 95 % confidence intervals (CI), and tests for trend were estimated using unconditional logistic regression. Results: There was a significant decrease in NHL risk with increased sun exposure at ages 13-21 years (OR ≥15 vs.≤3 h/week = 0.68; 95 % CI, 0.43-1.08; p trend = 0.0025), which attenuated for older ages at exposure. We observed significant main effect associations for 3 SNPs in VDR and 1 SNP in CYP24A1: rs886441 (OR per-allele = 0.82; 95 % CI, 0.70-0.96; p = 0.016), rs3819545 (OR per-allele = 1.24; 95 % CI, 1.10-1.40; p = 0.00043), and rs2239186 (OR per-allele = 1.22; 95 % CI, 1.05-1.41; p = 0.0095) for VDR and rs2762939 (OR per-allele = 0.85; 95 % CI, 0.75-0.98; p = 0.023) for CYP24A1. Moreover, the effect of sun exposure at age 13-21 years on overall NHL risk appears to be modified by germline variation in VDR (rs4516035; p interaction = 0.0066). Exploratory analysis indicated potential heterogeneity of these associations by NHL subtype. Conclusion: These results suggest that germline genetic variation in VDR, and therefore the vitamin D pathway, may mediate an association between early life sun exposure and NHL risk.

Original languageEnglish (US)
Pages (from-to)1017-1029
Number of pages13
JournalCancer Causes and Control
Volume23
Issue number7
DOIs
StatePublished - Jul 1 2012

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Keywords

  • Molecular epidemiology
  • Non-Hodgkin lymphoma
  • Ultraviolet radiation
  • VDR
  • Vitamin D

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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