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

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

Research output: Contribution to journalArticle

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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 (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 2012

Fingerprint

Solar System
Vitamin D
Non-Hodgkin's Lymphoma
Odds Ratio
Confidence Intervals
Genes
Alleles
Single Nucleotide Polymorphism
25-Hydroxyvitamin D3 1-alpha-Hydroxylase
Logistic Models
Vitamin D3 24-Hydroxylase

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Early life sun exposure, vitamin D-related gene variants, and risk of non-Hodgkin lymphoma. / Kelly, Jennifer L.; Drake, Matthew M; Fredericksen, Zachary S.; Asmann, Yan; Liebow, Mark; Shanafelt, Tait D.; Feldman, Andrew L; Ansell, Stephen Maxted; Macon, William R.; Herr, Megan M.; Wang, Alice H.; Nowakowski, Grzegorz S; Call, Timothy G.; Habermann, Thomas Matthew; Slager, Susan L; Witzig, Thomas Elmer; Cerhan, James R.

In: Cancer Causes and Control, Vol. 23, No. 7, 07.2012, p. 1017-1029.

Research output: Contribution to journalArticle

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keywords = "Molecular epidemiology, Non-Hodgkin lymphoma, Ultraviolet radiation, VDR, Vitamin D",
author = "Kelly, {Jennifer L.} and Drake, {Matthew M} and Fredericksen, {Zachary S.} and Yan Asmann and Mark Liebow and Shanafelt, {Tait D.} and Feldman, {Andrew L} and Ansell, {Stephen Maxted} and Macon, {William R.} and Herr, {Megan M.} and Wang, {Alice H.} and Nowakowski, {Grzegorz S} and Call, {Timothy G.} and Habermann, {Thomas Matthew} and Slager, {Susan L} and Witzig, {Thomas Elmer} and Cerhan, {James R}",
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AU - Drake, Matthew M

AU - Fredericksen, Zachary S.

AU - Asmann, Yan

AU - Liebow, Mark

AU - Shanafelt, Tait D.

AU - Feldman, Andrew L

AU - Ansell, Stephen Maxted

AU - Macon, William R.

AU - Herr, Megan M.

AU - Wang, Alice H.

AU - Nowakowski, Grzegorz S

AU - Call, Timothy G.

AU - Habermann, Thomas Matthew

AU - Slager, Susan L

AU - Witzig, Thomas Elmer

AU - Cerhan, James R

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N2 - 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.

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