Gene variations related to the hepatocellular carcinoma: Results from a field synopsis and Bayesian revaluation.

Hepatocellular carcinoma (HCC) is considered as the second cause of cancer-related deaths worldwide. Genetic variations are associated with HCC risk, an issue that has been the subject of several meta-analyses. However, meta-analyses have an important limitation on the likelihood of false positive data. Henceforth, this study aimed to assess the level of noteworthiness in the meta-analyses by means of a Bayesian approach. A systematic search was performed for meta-analyses with associations between gene polymorphisms and HCC. The calculations for the False-Positive Rate Probability (FPRP) and the Bayesian False Discovery Probability (BFDP) were performed to assess the noteworthiness with a statistical power of 1.2 and 1.5 of Odds Ratio at a prior probability of 10-3 and 10-5. The quality of studies was evaluated by the Venice criteria. As additional analyses, the gene-gene and protein-protein networks were designed for these genes and products. As results, we found 33 meta-analytic studies on 45 polymorphisms occurring in 35 genes. A total of 1,280 values for FPRP and BFDP were obtained. Seventy-five for FPRP (5.86%) and 95 for BFDP (14.79%) were noteworthy. In conclusion, the polymorphisms in CCND1, CTLA4, EGF, IL6, IL12A, KIF1B, MDM2, MICA, miR-499, MTHFR, PNPLA3, STAT4, TM6SF2, and XPD genes were considered as noteworthy biomarkers for HCC risk.

Assessing mercury intoxication in isolated/remote populations: Increased S100B mRNA in blood in exposed riverine inhabitants of the Amazon.

Mercury is a heavy metal responsible for human intoxication worldwide and especially in the Amazon, where both natural and anthropogenic sources are responsible for exposure in riverine populations. Methylmercury is the most toxic specie of mercury with recognized neurotoxicity due to its affinity for the central nervous system. S100B protein is a well-established biomarker of brain damage and it was recently associated with mercury-related neurotoxicity. Accurate measurement is especially challenging in isolated/remote populations due to the difficulty of adequate sample conservation, therefore here we use S100B mRNA levels in blood as a way to assay mercury neurotoxicity. We hypothesized that individuals from chronically exposed populations showing mercury levels above the limit of 10 µg/g in hair would present increased levels of S100B mRNA, likely due to early brain damage. A total of 224 riverine individuals were evaluated for anthropometric data (age, body mass index), self-reported symptoms of mercury intoxication, c-reactive protein in blood, and mercury speciation in hair. Approximately 20% of participants showed mercury levels above the limit, and prevalence for most symptoms was not different between individuals exposed to high or low mercury levels. Rigorous exclusion criteria were applied to avoid confounding factors and S100B mRNA in blood was tested by RT-qPCR. Participants with ≥10 µg/g of mercury had S100B mRNA levels over two times higher than that of individuals with lower exposure. A significant correlation was also detected between mercury content in hair and S100B mRNA levels in blood, supporting the use of the latter as a possible candidate to predict mercury-induced neurotoxicity. This is the first report of an association between S100B mRNA and mercury exposure in humans. The combination of both exposure and intoxication biomarkers could provide additional support for the screening and early identification of high-risk individuals in isolated populations and subsequent referral to specialized centers.