Toenail selenium, genetic variation in selenoenzymes and risk and outcome in glioma.

BACKGROUND: Selenium is an essential trace element obtained through diet that plays a critical role in DNA synthesis and protection from oxidative damage. Selenium intake and polymorphisms in selenoproteins have been linked to the risk of certain cancers though data for glioma are sparse. METHODS: In a case-control study of glioma, we examined the associations of selenium in toenails and genetic variants in the selenoenzyme pathway with the risk of glioma and patient survival. A total of 423 genetic variants in 29 candidate genes in the selenoenzyme pathway were studied in 1547 glioma cases and 1014 healthy controls. Genetic associations were also examined in the UK Biobank cohort comprised of 313,868 persons with 322 incident glioma cases. Toenail selenium was measured in a subcohort of 300 glioma cases and 300 age-matched controls from the case-control study. RESULTS: None of the 423 variants studied were consistently associated with glioma risk in the case-control and cohort studies. Moreover, toenail selenium in the case-control study had no significant association with glioma risk (p trend = 0.70) or patient survival among 254 patients with high grade tumors (p trend = 0.70). CONCLUSION: The present study offers no support for the hypothesis that selenium plays a role in the onset of glioma or patient outcome.

Metabolomic Profiling of Serum Retinol in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study.

The role of retinol in the prevention of multifactorial chronic diseases remains uncertain, and there is sparse evidence regarding biological actions and pathways implicated in its effects on various outcomes. The aim is to investigate whether serum retinol in an un-supplemented state is associated with low molecular weight circulating metabolites. We performed a metabolomic analysis of 1,282 male smoker participants based on pre-supplementation fasting serum in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. We examined the association between 947 metabolites measured by ultra-high performance LC-MS/GC-MS and retinol concentration (from HPLC) using linear regression that estimated the difference in metabolite concentrations per unit difference in retinol concentration as standardized ß-coefficients and standard errors (SE). We identified 63 metabolites associated with serum retinol below the Bonferroni-corrected P-value (p < 5.3 × 10-5). The strongest signals were for N-acetyltryptophan (ß = 0.27; SE = 0.032; p = 9.8 × 10-17), myo-inositol (ß = 0.23; SE = 0.032; p = 9.8 × 10-13), and 1-palmitoylglycerophosphoethanolamine (ß = 0.22; SE = 0.032; p = 3.2 × 10-12). Several chemical class pathways were strongly associated with retinol, including amino acids (p = 1.6 × 10-10), lipids (p = 3.3 × 10-7), and cofactor/vitamin metabolites (3.3 × 10-7). The strongest sub-pathway association was for inositol metabolism (p = 2.0 × 10-14). Serum retinol concentration is associated with circulating metabolites in various metabolic pathways, particularly lipids, amino acids, and cofactors/vitamins. These interrelationships may have relevance to the biological actions of retinol, including its role in carcinogenesis.

Metabolomics analysis of serum 25-hydroxy-vitamin D in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study.

BACKGROUND: Vitamin D has been discussed in the context of cardiovascular disease, cancer, bone health and other outcomes. Epidemiological studies have reported on the importance of vitamin D in cancer prevention and treatment. The discovery of vitamin D-associated metabolites through agnostic metabolomics analyses offers a new approach for elucidating disease aetiology and health-related pathway identification. METHODS: Baseline serum 25-hydroxy-vitamin D [25(OH)D] and 940 serum metabolites were measured in 392 men from eight nested cancer case-control studies in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of Finnish male smokers (aged 50-69 years). The metabolomic profiling was conducted using mass spectrometry. We used linear regression to estimate the standardized beta-coefficient as the effect metric for the associations between metabolites and 25(OH)D levels. RESULTS: A majority of the metabolites associated with 25(OH)D were of lipid origin, including 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) [beta-estimate 0.38 per 1 standard deviation (SD) increment], stearoyl-arachidonoyl-glycerophosphoethanolamine (GPPE) (-0.38 per SD) and two essential fatty acids: eicosapentaenoate (EPA; 0.17 per SD) and docosahexaenoate (DHA; 0.13 per SD). Each of these lipid metabolites was associated with 25(OH)D at the principal components corrected P-value of 3.09 × 10-4 CONCLUSIONS: The large number of metabolites, particularly lipid compounds, found to be associated with serum 25(OH)D provide new biological clues relevant to the role of vitamin D status and human health outcomes. The present findings should be re-examined in other metabolomics studies of diverse populations.