Open AccessInverse association of vitamin D 3 levels with lung cancer mediated by genetic variation
Author(s) -
Haznadar Majda,
Krausz Kristopher W.,
Margono Ezra,
Diehl Christopher M.,
Bowman Elise D.,
Manna Soumen Kanti,
Robles Ana I.,
Ryan Bríd M.,
Gonzalez Frank J.,
Harris Curtis C.
Publication year - 2018
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.1444
Subject(s) - lung cancer , vitamin d and neurology , medicine , quartile , endocrinology , population , micronutrient , cohort , vitamin d deficiency , gastroenterology , confidence interval , pathology , environmental health
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 )D 2/3 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 D 2/3 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 )D 3 levels were inversely associated with lung cancer status across quartiles (Q2 vs. Q1: OR adjusted = 0.5, 95% CI = 0.3–0.8; Q3 vs. Q1: OR adjusted = 0.5, 95% CI = 0.3–0.8; Q4 vs. Q1: OR adjusted = 0.5, 95% CI = 0.2–0.9; P trend = 0.004). Levels of 1,25( OH ) 2 D 3 were also inversely associated with lung cancer status (Q2 vs. Q1: OR adjusted = 0.2, 95% CI = 0.03–0.7; Q3 vs. Q1: OR adjusted = 0.1, 95% CI = 0.01–0.4; Q4 vs. Q1: OR adjusted = 0.04, 95% CI = 0.01–0.3; P trend <0.0001). Although the observed trends were similar for the 25( OH )D 2 ( P trend = 0.08), no significant associations were seen between vitamin D 2 and lung cancer status. Additionally, genotyping of 296 SNP s in the same subjects resulted in findings that 27 SNP s, predominantly in CYP 24A1 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 D 3 in lung cancer, with similar trends but insignificant findings for D 2 . Vitamin D 3 levels appeared to be modulated by genetic variation in CYP 24A1 and VDR genes. Additional research to illuminate the mechanism(s) through which vitamin D exacerbates effects against lung carcinogenesis is warranted.