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.
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.
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; ptrend = 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; pinteraction = 0.0066). Exploratory analysis indicated potential heterogeneity of these associations by NHL subtype.
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.