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

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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 (ORper-allele = 0.82; 95 % CI, 0.70–0.96; p = 0.016), rs3819545 (ORper-allele = 1.24; 95 % CI, 1.10–1.40; p = 0.00043), and rs2239186 (ORper-allele = 1.22; 95 % CI, 1.05–1.41; p = 0.0095) for VDR and rs2762939 (ORper-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.

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Acknowledgments

We thank Sondra Buehler for her editorial assistance. This work was supported by awards from the National Institutes of Health, National Cancer Institute [R01 CA92153; P50 CA97274]. Dr. Kelly was supported by the National Institutes of Health, National Heart, Lung, and Blood Institute [HL007152], National Cancer Institute [P50 CA130805] and is a Lymphoma Research Foundation Fellow.

Conflicts of interest

No potential conflicts of interest were disclosed.

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Authors and Affiliations

  1. School of Medicine and Dentistry, University of Rochester, 601 Elmwood Avenue, Box 704, Rochester, NY, USA

    Jennifer L. Kelly & Megan M. Herr

  2. Department of Health Sciences Research, College of Medicine, Mayo Clinic, 200 First St SW, Rochester, MN, 55905, USA

    Matthew T. Drake, Zachary S. Fredericksen, Yan W. Asmann, Mark Liebow, Tait D. Shanafelt, Andrew L. Feldman, Stephen M. Ansell, William R. Macon, 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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  1. Jennifer L. Kelly
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Correspondence to James R. Cerhan.

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Kelly, J.L., Drake, M.T., Fredericksen, Z.S. et al. Early life sun exposure, vitamin D-related gene variants, and risk of non-Hodgkin lymphoma. Cancer Causes Control 23, 1017–1029 (2012). https://doi.org/10.1007/s10552-012-9967-0

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  • DOI: https://doi.org/10.1007/s10552-012-9967-0

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