ABSTRACT
Abstract: Objective: To determine the exposure to aflatoxin B1 (AFB1) in southern Mexico and the presence of the aflatoxin signature mutation in hepatocellular carcinoma (HCC) tissue from patients from a cancer referral center. Materials and methods: We estimated the prevalence and distribution of AFB1 in a representative sample of 100 women and men from Chiapas using the National Health and Nutrition Survey 2018-19. We also examined the presence of the aflatoxin signature mutation in codon 249 (R249S), and other relevant mutations of the TP53 gene in HCC tissue blocks from 24 women and 26 men treated in a national cancer referral center. Results: The prevalence of AFB1 in serum samples was 85.5% (95%CI 72.1-93.1) and the median AFB1 was 0.117 pg/µL (IQR, 0.050-0.350). We detected TP53 R249S in three of the 50 HCCs (6.0%) and observed four other G>T transversions potentially induced by AFB1. Conclusion: Our analysis provides evidence that AFB1 may have a relevant role on HCC etiology in Mexico.
Resumen: Objetivo: Determinar la exposición a aflatoxina_B1 (AFB1) en el sur de México y la presencia de la mutación característica de AFB1 en tejido de carcinoma hepatocelular (CHC) de pacientes de un centro oncológico. Material y métodos: Se estimó la prevalencia y distribución de AFB1 en una muestra representativa de 100 mujeres y hombres de Chiapas a partir de la Encuesta Nacional de Salud y Nutrición 2018-19. También se observó la presencia de la mutación característica de AFB1 en el codón 249 (R249S), y otras mutaciones relevantes del gen TP53 en bloques de tejido de CHC de 24 mujeres y 26 hombres estudiados en un centro de referencia nacional de oncología. Resultados: La prevalencia de AFB1 en las muestras de suero fue de 85.5% (IC95% 72.1-93.1) y la mediana de la concentración 0.117 pg/µL (IQR, 0.050-0.350). Se detectó TP53 R249S en tres de 50 casos de CHC (6.0%) y se observaron cuatro transversiones G>T potencialmente inducidas por AFB1. Conclusión: El presente análisis proporciona evidencia de que la AFB1 puede tener un papel relevante en la etiología del CHC en México.
ABSTRACT
Objectives: Micronutrient deficiencies are common but remain ‘hidden' due to difficulty of assessment. We explored the plasma proteome to identify nutrient-correlated biomarkers that may predict multiple micronutrient status and deficiencies, possibly on a single platform in the future. Methods: We measured, in 500 6-8 year old Nepalese children, plasma concentrations of >20 vitamin/mineral indicators and acute phase proteins (APP) by conventional assays, and relative abundance of proteins by quantitative mass spectrometry, bioinformatics and linear mixed effects models (Herbrich S et al, 2012; Cole R et al, 2013). We identified ~980 proteins in >10% of subjects, and evaluated their strength of correlation with micronutrient and APP distributions. Comparisons were corrected for multiple comparisons, with a 10% threshold for false discoveries. Results: 142 proteins were correlated with plasma retinol, 6 with 25(OH) vitamin D, 119 with α- tocopherol, 12 with γ-tocopherol, 6 with PIVKA-II (reflecting vitamin K status), 89 for vitamin B6, 35 for ferritin and 7 for transferrin receptor (reflecting iron status), 232 for copper, 3 for selenium and none for folate, thyroglobulin (reflecting iodine status) or vitamin B12 (q>0.1 for all comparisons). Initial models with up to 6 covariates suggest an ability to explain 60-80% of the variation (R2) in retinol, α-tocopherol, vitamin B6 and copper, ~50% of the variation in ferritin and, the carotenoid, β-cryptoxanthin and 80-85% of variation in CRP and AGP. Other nutrient-protein models will be presented. Conclusions: Plasma nutrient-correlated proteomes exist that, with absolute quantification of candidate proteins, could provide a basis for multiple micronutrient status assessment of populations in the future.
ABSTRACT
Objectives: Antenatal micronutrient interventions may influence maternal and offspring health in chronically undernourished settings; however, molecular mechanisms remain largely unexplored. We examined effects of multiple combinations of antenatal micronutrients as supplements on the plasma proteome of offspring at 6-8 years of age. Methods: We applied quantitative mass spectrometry to measure plasma protein abundance in 500 children whose mothers had been randomized to receive daily supplements of folic acid (FA), iron-folic acid (IFA), iron-folic acid-zinc (IFAZn), multiple micronutrient (MM), or placebo (control) from 1st trimester to 3 months postpartum (all tablets contained vitamin A). We identified differentially abundant proteins and sets of proteins sharing a common biological function by enrichment analysis using the Gene Ontology (GO) database. Results: With a relaxed discovery threshold (false discovery rate <0.25), maternal FA supplementation increased the abundance of insulin-like growth factor-1 (IGF1) by 33.7 (95% CI: 14.7-55.8)%; maternal IFA supplementation increased tissue inhibitor of metalloproteinase 1 by 12.5 (5.9-19.6)%. All supplements containing iron-folic acid increased IGF1, IGF2, and IGFbinding protein 5 by 23.9 (9.1-40.7)%, 28.6 (10.7-49.4)%, and 23.7 (10.5-38.5)%, respectively, and decreased stromal interaction molecule 1 by 63.3 (36.7-78.8)%. With a discovery threshold of 0.05, maternal IFA supplementation negatively enriched proteins localized in microtubules (GO:5874) with an enrichment score (ES) of -0.62 and maternal IFA and MM supplementation positively enriched proteins with growth factor activity (GO:8083) with ES of 0.70 and 0.75, respectively (all p-values <0.0001). Conclusions: Antenatal micronutrient supplementation exerts subtle metabolic effects on proteins involved in regulating growth/development and intracellular structure in school-aged children.