Abstract 3682: Response of biomarkers of inflammation (IL-8,TNF-α, sTNFRI & II) to cruciferous vegetable feeding in a controlled diet study in humans: Effects of GSTM1 and GSTT1 genotypes

Abstract

Abstract Isothiocyanates (ITC) in cruciferous vegetables modulate several signaling pathways involved in carcinogenesis, including nuclear factor kappa-B (NF-κB), a transcription factor and central mediator in the generation of inflammation. Glutathione S-transferase (GST)M1 & GSTT1 metabolize ITC; genotypic differences in biologic response to cruciferous vegetable intake, and variation in ITC pharmacokinetics have been reported. Previously, we found reduced serum IL-6 and CRP concentrations in response to cruciferous (broccoli family) and apiaceous (carrot family) vegetable feeding compared to a basal diet in a randomized, crossover trial. Reductions were most marked among individuals with a GSTM1-null genotype. Here, we extend our panel of biomarkers in this intervention to include serum interleukin (IL)-8, tumor necrosis factor-alpha (TNF-α), and soluble TNF receptors I & II (sTNFRI & II). We tested whether supplementation of cruciferous or apiaceous vegetables alters serum concentrations of these markers, and whether this response is GSTM1/GSTT1 genotype-dependent. Men (n=26) and women (n=30), 20-40 y, ate four 14-day controlled diets – basal (fruit &vegetable-free), basal + two doses of crucifers (single & double “dose”), and single-dose cruciferous + apiaceous vegetables – fed per kg body weight. Fasting bloods from days 0 & 14 of each period were analyzed for serum inflammatory markers (IL-8 & TNF-a using the High Sensitivity Human Cytokine Panel, sTNFRs using the Human Soluble Cytokine Receptor Panel, Millipore). In this healthy population, we observed no overall reduction in any of the current biomarkers in response to vegetable supplementation. However, similarly to what we observed with IL-6 and CRP, both sTNFRI & II were lower at day 14 on the double-dose cruciferous vegetable diet among GSTM1-null individuals (P=0.006 & 0.007, respectively). NF-kB is one regulator of these inflammatory markers; but overlap with other pro-inflammatory pathways that may be differently regulated by diet, e.g., STAT3, may preclude observation of an effect. Such diet interventions may be more effective in populations with higher circulating inflammation biomarkers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3682. doi:10.1158/1538-7445.AM2011-3682