Abstract 670: Cigarette smoking, race, and genetic ancestry in association with plasma vitamin D-binding protein (VDBP) in healthy African Americans (AA) and Caucasian Americans (CA)

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Vitamin D and VDBP affect several pathways involved in inflammation, tumor growth, and immune surveillance relevant to carcinogenesis. In a previous pilot study (Bortner et al., 2010), using a proteomics approach, VDBP was down-regulated in the plasma of chronic cigarette smokers by as much as 3-fold. Therefore, using an existing study of healthy AA and CA participants, we conducted an investigation of the differences in VDBP between 39 current smokers and 82 never smokers, frequency matched on age, sex and race/ethnicity. VDBP plasma concentrations were determined in duplicate using the Quantikine® Human VDBP ELISA (CV%, 5.6%). Genotyping was conducted for a set of 112 previously validated Ancestry Informative Markers for the percent West African and European genetic ancestry, and VDBP coding region changes via rs7041 (Asp416Glu, T/G) and rs4588 (Thr420Lys, C/A). Vitamin D metabolites (25OHD3 and 24,25(OH)2D3) were determined using LC-MS/MS (CV% 2.7 and 6.3, respectively). T-test, Chi-Square, Fisher's Exact, and Spearman's correlation coefficients were used to determine statistically significant bivariate differences. Multiple logistic regression was used to adjust for multiple factors using the log-normal transformation of VDBP concentration with the Cochran-Armitage test for trend for VDBP genotype. Multiplicative interaction terms were tested along with their main-effects, adjusted for co-variates. There were no significant differences between current smokers and never smokers by age, VDBP genotype, body mass index, vitamin D metabolites, or genetic ancestry. VDBP concentrations were significantly negatively correlated with body mass index (BMI, r=−0.19, p=0.033), West African ancestry (r=−0.66, p<0.001), vitamin D metabolites (p-values<0.001), VDBP rs4588-A and rs7041-T alleles (VDBP genotypes were 100% correlated). VDBP genotypes coding Asp416Asp and Lys420Lys were at least 3.3-fold lower, compared with Glu416Glu and Thr420Thr, respectively, and this was regardless of smoking status (p-trend<0.001). There was no association between VDBP concentration and age or smoking status. In multiple regression models, serum vitamin D metabolites, self-reported race/ethnicity, West African ancestry and GC genotypes remained significantly associated with VDBP concentration. The magnitude of difference in these variables was similar among current and never smokers, although BMI remained significantly negatively associated with VDBP concentrations among never smokers (p-interaction =0.028). Smoking status was not highly correlated with VDBP plasma concentration, although may have some interactive effect with BMI. Future studies will need to account for the strong correlations with VDBP genotype and genetic ancestry. Support: 1K22CA120092-01A2 and 3K22CA120092-02S1. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 670. doi:1538-7445.AM2012-670