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This study highlights a novel role for HAMP downregulation through DNA promoter hypermethylation and emphasises the significance of epigenetics in the regulation of iron metabolism in HCC.

Colon cancer is one of the most frequent solid tumor and simultaneous diagnosis of primary colon cancer and liver metastases occurs in about one fourth of cases. The current knowledge on epigenetic signatures, especially those related to hydroxymethylation in primary cancer tissue, synchronous metastasis, and blood circulating cells is lacking. This study aimed to investigate both methylcytosine (mCyt) and hydroxymethylcytosine (hmCyt) status in the DNA of individual patients from colon cancer tissue, synchronous liver metastases, and in cancer-free colon and liver tissues and leukocytes. Patients undergoing curative surgery (n = 16) were enrolled and their laboratory and clinical history data collected. The contents of mCyt and hmCyt were determined by a liquid chromatography/mass spectrometry (LC/MS/MS) method in DNA extracted from primary colon cancer, synchronous hepatic metastatic tissues and homologous cancer-free tissues, i.e., colon and liver tissues as well as leukocytes. The mCyt and hmCyt levels were compared between cancerous and cancer-free tissues, and correlations between leukocytes and colon/liver tissues for both the mCyt and hmCyt levels were evaluated. The mCyt levels were similar in primary colon cancer and liver metastasis tissues (4.69 ± 0.37% vs. 4.77 ± 0.38%, respectively, p = 0.535), and both primary and metastatic tissues were hypomethylated compared to cancer-free colon (4.98 ± 0.26%). The difference in the mCyt content between cancerous and cancer-free colon tissues was significantly lower in primary colon cancer (p = 0.004), but not in liver metastasis (p = 0.148). The hmCyt content was similar in primary colon cancer compared to liver metastasis (0.035%, C.I. 0.024–0.052% versus 0.035%, C.I. 0.021–0.058%, respectively, p = 0.905) and markedly depleted compared to the cancer-free colon (0.081%, C.I. 0.055–0.119%) with a statistically significant difference (p < 0.05) for both comparisons. The mCyt levels showed a borderline correlation between leukocytes and colon cancer tissue (Pearson’s correlation coefficient = 0.51, p = 0.052) while no correlations were detected for the hmCyt levels. In conclusion, primary colon cancer and synchronous liver metastasis tissues showed a similar epigenetic status but were significantly hypomethylated and hypohydroxymethylated as compared to homologous cancer-free colon tissues.

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Objective: The aim of this study was to investigate whether 4 functional single nucleotide polymorphisms (SNPs) in glutathione peroxidases (GPX1 and GPX4) and selenoprotein P (SEPP) modify the effect of intervention with selenium-rich foods on concentrations of blood selenium and selenoprotein expression (erythrocyte GPX activity and plasma SEPP concentration).Methods: In a parallel dietary intervention study 83 healthy men and women aged 50-74 y were randomly assigned to either a control or an intervention group. Participants in the intervention group were provided with 5 portions of 200 g raw fish and shellfish once a week for 26 wk, corresponding to ∼50.3 μg Se/d. The participants in the control group received no intervention and were advised to maintain their habitual diets. Selected functional polymorphisms were GPX1/rs1050450, GPX4/rs713041, SEPP1/rs3877899, and SEPP1/rs7579. Genotypes were determined through the use of reverse transcriptase-polymerase chain reaction and allelic discrimination on ABI 7900HT instruments. Samples were run in duplicates with known positive controls and 3 negative controls. Duplicates yielded 100% identical genotypes. Whole-blood selenium analyses were conducted by inductively coupled plasma mass spectrometry with an ELAN 6100 DRC, and plasma SEPP concentration was determined from its selective retention by heparin-affinity HPLC and online detection by inductively coupled plasma dynamic reaction cell mass spectrometry of selenium. GPX activity was spectrophotometrically assayed in erythrocyte lysates on a Pentra 400 with t-butylhydroperoxide as substrate and related to the amount of hemoglobin in the lysates.Results: The intervention diet resulted in higher concentrations of both SEPP (P = 0.018) and blood selenium (P = 0.088) in wild-type allele carriers of the SEPP1/rs3877899 polymorphism compared with variant allele carriers. None of the other polymorphisms modified the biomarker responses following the intervention. Carriers of the variant GPX1 allele had significantly lower erythrocyte GPX enzyme activity compared with wild-type carriers independent of intervention.Conclusions: Our study shows that variation in the SEPP1 gene modifies biomarkers of selenium status after intake of selenium-rich foods. This opens the way for a more personalized approach to micronutrient requirements. Funding SourcesNone. Interactions between Diets High in Cholesterol and Dioxin-Like Pollutants Increase Inflammation, Disrupt Gut Microbiota, and Modulate Host Metabolism (E14-02)Jessie Hoffman, Michael Petriello, Olga Vsevolozhskaya, Richard Charnigo, Pan Deng, Andrew Morris, and Bernhard Hennig University of KentuckyObjective: The gut microbiome is sensitive to diet and environmental exposures and is involved in the regulation of many host metabolic responses. Exposures to dioxin-like pollutants occur primarily via ingestion of contaminated foods and are linked to increased risk of developing metabolic diseases. Our objective was to elucidate the effects of the dioxin-like 1 Downloaded from h...