Vitamin D is an essential
micronutrient required for normal physiological function and recognized for its role regulating
calcium metabolism. Recent work is beginning to emerge demonstrating a role for
vitamin D in
chronic illnesses, such as
cancer. Circulating serum levels of 25(
OH)D2/3 were quantitatively measured using sensitive ultraperformance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) in 406
lung cancer cases and 437 population controls, while 1,25(
OH)2 D2/3 levels were measured in a subset of 90 cases and 104 controls using the same method, from the NCI-MD case-control cohort. 25(
OH)D3 levels were inversely associated with
lung cancer status across quartiles (Q2 vs. Q1: ORadjusted = 0.5, 95% CI = 0.3-0.8; Q3 vs. Q1: ORadjusted = 0.5, 95% CI = 0.3-0.8; Q4 vs. Q1: ORadjusted = 0.5, 95% CI = 0.2-0.9; Ptrend = 0.004). Levels of 1,25(
OH)2 D3 were also inversely associated with
lung cancer status (Q2 vs. Q1: ORadjusted = 0.2, 95% CI = 0.03-0.7; Q3 vs. Q1: ORadjusted = 0.1, 95% CI = 0.01-0.4; Q4 vs. Q1: ORadjusted = 0.04, 95% CI = 0.01-0.3; Ptrend <0.0001). Although the observed trends were similar for the 25(
OH)D2 (Ptrend = 0.08), no significant associations were seen between
vitamin D2 and
lung cancer status. Additionally, genotyping of 296 SNPs in the same subjects resulted in findings that 27 SNPs, predominantly in
CYP24A1 and VDR genes, were significantly associated with
lung cancer status, affected
mRNA expression, and modulated
vitamin D levels. These findings suggest a protective role for
vitamin D3 in
lung cancer, with similar trends but insignificant findings for D2 .
Vitamin D3 levels appeared to be modulated by genetic variation in
CYP24A1 and VDR genes. Additional research to illuminate the mechanism(s) through which
vitamin D exacerbates effects against lung
carcinogenesis is warranted.