Abstract 4320: Circulating vitamin D2 and D3 levels and single nucleotide polymorphism associations with lung cancer status: A case-control study
Authors: Majda Haznadar, Kristopher W. Krausz, Ezra Margono, Elise D. Bowman, Brid M. Ryan, Frank J. Gonzalez, Curtis C. Harris
Journal: Cancer Research (2016)

Abstract Vitamin D is an essential micronutrient, required for normal physiological function and classically recognized for its role regulating calcium metabolism. Recent work is beginning to demonstrate a role of vitamin D in chronic illnesses, such as cancer, but questions addressing how depletion of this nutrient affects cancer risk remain largely unanswered. In 2011, the Institute of Medicine report highlighted the need for more research to explore the role of vitamin D in non-skeletal health outcomes. Previously, vitamin D has largely been measured using radio- and chemiluminescence immunoassays, unable to distinguish between D2 (from plant dietary sources and supplements) and D3 forms. We measured circulating serum levels of both, inactive (25(OH)D), and active (1,25(OH)2D) forms of D2 and D3 using sensitive liquid chromatography coupled to mass spectrometry in 406 lung cancer cases and 437 controls. We observed that levels of inactive D3 are associated with decreased lung cancer risk across quartiles, after adjustment for age, gender, race, smoking status, pack years, interview year and blood collection month (ORadjusted = 0.5 (95% CI = 0.2, 0.9), P &amp;lt; 0.02; Ptrend &amp;lt;0.0001), compared with the lowest quartile. The observed associations remained significant upon stratifications on race, with ORadjusted ranging from 0.4 to 0.3 (95% CI = 0.1, 0.9), P &amp;lt; 0.04 in 2nd and 3rd quartiles, respectively, in African Americans, and ORadjusted = 0.5, P = 0.04 in 4th quartile in European Americans. Increasing levels of active D3 were associated with decreased lung cancer risk (ORadjusted ranging from 0.2 to 0.04 (95% CI = 0.01, 0.7), P &amp;lt; 0.01; Ptrend &amp;lt; 0.0001). High levels of inactive D2 were associated with decreased lung cancer risk only in the highest when compared to the lowest quartile (ORadjusted = 0.5 (95% CI = 0.2, 0.9), P = 0.05); no significant observations were seen for the active D2. Additionally, we conducted comprehensive genotyping of single nucleotide polymorphisms (SNPs) in the genes from the vitamin D metabolism pathway (CYP2R1, CYP27A1, CYP27B1, CYP24A1, and VDR), with a minor allele frequency of ≥5%, using a Fluidigm platform. Of 261 SNPs, 21 were associated with lung cancer risk. Four SNPs in VDR were found to modulate vitamin D3 levels in the controls: alleles associated with increased risk were associated with decreased vitamin D levels and vice versa, suggesting their functional significance in the context of lung cancer. We are the first group to investigate physiological levels of both, inactive and active forms of D2 and D3 in cancer patients. Our findings suggest a protective role of vitamin D in lung cancer, with stronger associations observed for D3, and reinforce the importance of maintaining optimal levels of this crucial vitamin for human health. Additional research to illuminate the mechanism through which vitamin D contributes to lung cancer carcinogenesis is warranted. Citation Format: Majda Haznadar, Kristopher W. Krausz, Ezra Margono, Elise D. Bowman, Brid M. Ryan, Frank J. Gonzalez, Curtis C. Harris. Circulating vitamin D2 and D3 levels and single nucleotide polymorphism associations with lung cancer status: A case-control study. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4320.