title: Early life sun exposure, vitamin D-related gene variants, and risk of non-Hodgkin lymphoma.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: School of Medicine and Dentistry, University of Rochester, NY, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Kelly
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Drake
authors.forename: Zachary S
authors.initials: ZS
authors.lastname: Fredericksen
authors.forename: Yan W
authors.initials: YW
authors.lastname: Asmann
authors.forename: Mark
authors.initials: M
authors.lastname: Liebow
authors.forename: Tait D
authors.initials: TD
authors.lastname: Shanafelt
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Feldman
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Ansell
authors.forename: William R
authors.initials: WR
authors.lastname: Macon
authors.forename: Megan M
authors.initials: MM
authors.lastname: Herr
authors.forename: Alice H
authors.initials: AH
authors.lastname: Wang
authors.forename: Grzegorz S
authors.initials: GS
authors.lastname: Nowakowski
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Call
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Habermann
authors.forename: Susan L
authors.initials: SL
authors.lastname: Slager
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Witzig
authors.forename: James R
authors.initials: JR
authors.lastname: Cerhan
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism; D047488:Retinoid X Receptors / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors; D013250:Steroid Hydroxylases / Q000235:genetics / Q000378:metabolism; D013472:Sunlight; D011795:Surveys and Questionnaires; D013997:Time Factors; D014807:Vitamin D / Q000378:metabolism*; D065668:Vitamin D3 24-Hydroxylase; D055815:Young Adult
chemical_list: D018167:Receptors, Calcitriol; D047488:Retinoid X Receptors; D014807:Vitamin D; D013250:Steroid Hydroxylases; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase