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Inverse association of vitamin D3 levels with lung cancer mediated by genetic variation.
Cancer Med. 2018 Jun; 7(6):2764-2775.CM

Abstract

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.

Links

Authors+Show Affiliations

Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, 20892.

Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, 20892.

Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, 20892.

Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, 20892.

Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, 20892.

Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics (HBNI), Kolkata, 700064, India.

Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, 20892.

Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, 20892.

Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, 20892.

Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, 20892.

MeSH

AgedCase-Control StudiesCholecalciferolChromatography, LiquidFemaleGenetic VariationGenotypeHumansLung NeoplasmsMaleMetabolomicsMiddle AgedOdds RatioPolymorphism, Single NucleotideTandem Mass SpectrometryVitamin D3 24-Hydroxylase

Pub Type(s)

Journal Article

Research Support, N.I.H., Extramural

Language

eng

PubMed ID

29726119

Citation

Haznadar, Majda, et al. "Inverse Association of Vitamin D3 Levels With Lung Cancer Mediated By Genetic Variation." Cancer Medicine, vol. 7, no. 6, 2018, pp. 2764-2775.

Haznadar M, Krausz KW, Margono E, et al. Inverse association of vitamin D3 levels with lung cancer mediated by genetic variation. Cancer Med. 2018;7(6):2764-2775.

Haznadar, M., Krausz, K. W., Margono, E., Diehl, C. M., Bowman, E. D., Manna, S. K., Robles, A. I., Ryan, B. M., Gonzalez, F. J., & Harris, C. C. (2018). Inverse association of vitamin D3 levels with lung cancer mediated by genetic variation. Cancer Medicine, 7(6), 2764-2775. https://doi.org/10.1002/cam4.1444

Haznadar M, et al. Inverse Association of Vitamin D3 Levels With Lung Cancer Mediated By Genetic Variation. Cancer Med. 2018;7(6):2764-2775. PubMed PMID: 29726119.

* Article titles in AMA citation format should be in sentence-case

TY - JOUR T1 - Inverse association of vitamin D3 levels with lung cancer mediated by genetic variation. AU - Haznadar,Majda, AU - Krausz,Kristopher W, AU - Margono,Ezra, AU - Diehl,Christopher M, AU - Bowman,Elise D, AU - Manna,Soumen Kanti, AU - Robles,Ana I, AU - Ryan,Bríd M, AU - Gonzalez,Frank J, AU - Harris,Curtis C, Y1 - 2018/05/03/ PY - 2017/10/24/received PY - 2018/02/11/revised PY - 2018/02/19/accepted PY - 2018/5/5/pubmed PY - 2019/10/30/medline PY - 2018/5/5/entrez KW - SNP KW - 1,25(OH)D KW - 25(OH)2D KW - CYP24A1 KW - lung cancer status KW - serum KW - vitamin D SP - 2764 EP - 2775 JF - Cancer medicine JO - Cancer Med VL - 7 IS - 6 N2 - 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. SN - 2045-7634 UR - https://www.unboundmedicine.com/medline/citation/29726119/full_citation DB - PRIME DP - Unbound Medicine ER -