The serum microRNAs have been reported as potential biomarkers for hepatocellular carcinoma (HCC); however, their role in genic toxicity related to aflatoxin B1 (AFB1), such as TP53 mutation and DNA damage, has not yet been evaluated. Here, we conducted a hospital-based case-control study, including 558 patients with pathologically diagnosed HCC and positive AFB1 and healthy controls (n = 630) without any evidence of liver diseases. Genic toxicity related to AFB1 was evaluated using the hot-spot mutation at the codon 269 of TP53 gene (TP53M) and AFB1-DNA adducts. Through serum microRNA PCR microarray screening analysis, we observed 10 differentially expressed microRNAs (including miR-7-2-3p, miR-4651, miR-127-3p, miR-192-5p, miR-382-5p, miR-10b-5p, miR-532-3p, miR-16-5p, miR-106b-5p, and miR-4688) among HCC cases with positive AFB1 and controls with positive AFB1. The miR-4651 and miR-382-5p were further identified to be significantly higher in AFB1-positive HCC cases compared to controls. This kind of increasing serum levels was significantly and positively associated with frequency of TP53M and the levels of AFB1-DNA adduct. Furthermore, these microRNAs also modified the prognosis of HCC related to AFB1. These results suggest that the serum levels of microRNAs might be able to modify AFB1-induced genic toxicity, and microRNA-4651 and miR-382-5p, are such potential candidates.
Part of the book: Aflatoxin
Aflatoxin B1 (AFB1) is an important environmental carcinogen for the development of hepatocellular carcinoma (HCC). HCC is a complex disease likely resulting from genetic single nucleotide polymorphisms (GSNPs) of multiple interacting genes and gene-environment interactions. Recent efforts have been made to analyze the associations between risk of this malignancy and GSNPs in genes involved in the repair of DNA damage induced by AFB1. Here, we reviewed the results of published case-control studies that have examined the effects of common alleles of all susceptible DNA repair genes, including XRCC1, XRCC3, XRCC4, XRCC7, XPC, and XPD, on risk of AFB1-related HCC among Guangxi population. Statistically significant differences in genotype frequencies found in case-control comparisons were rs25487, rs80309960, rs861539, rs7003908, rs28383151, rs3734091, rs13181, and rs2228001 polymorphism. The overall effects of these GNSPs were moderate in terms of relative risk, with ORs ranging from 2 to 10. Furthermore, some evidence of the interaction of GSNPs in DNA repair genes and AFB1 exposure modulate risk of this cancer was also found, although the results require confirmation with larger sample size studies.
Part of the book: Genetic Polymorphisms
Hepatocellular carcinoma (also termed hepatocarcinoma) is the third cancer-related cause of death worldwide. To our knowledge, markers such as α-fetoprotein display poor performance in the early diagnosis and prognosis prediction of hepatocarcinoma. MicroRNAs are an evolutionarily conserved class of small noncoding single-stranded RNA typically consisting of 18–24 nucleotides. They have been reported to act as tumor suppressors or oncogenes via reversely regulating gene expression. Recent evidence has revealed that microRNAs, especially in body fluids such as the blood and urine, display important diagnostic and prognostic potential for hepatocarcinoma. Here, we reviewed currently available data on microRNAs and hepatocarcinoma, with emphasis on the biogenesis and function of microRNAs and their potential diagnostic and prognostic value for hepatocarcinoma. We also discussed the clinical utility perspectives of microRNAs in hepatocarcinoma and possible challenges.
Part of the book: Hepatocellular Carcinoma
Hepatocellular carcinoma (hepatocarcinoma) is a major type of primary liver cancer and one of the most frequent human malignant neoplasms. Aflatoxins are I-type chemical carcinogen for hepatocarcinoma. Increasing evidence has shown that hepatocarcinoma induced by aflatoxins is the result of interaction between aflatoxins and hereditary factor. Aflatoxins can induce DNA damage including DNA strand break, adducts formation, oxidative DNA damage, and gene mutation and determine which susceptible individuals feature cancer. Inheritance such as alterations may result in the activation of proto-oncogenes and the inactivation of tumor suppressor genes and determine individual susceptibility to cancer. Interaction between aflatoxins and genetic susceptible factors commonly involve in almost all pathologic sequence of hepatocarcinoma: chronic liver injury, cirrhosis, atypical hyperplastic nodules, and hepatocarcinoma of early stages. In this review, we discuss the biogenesis, toxification, and epidemiology of aflatoxins and signal pathways of aflatoxin-induced hepatocarcinoma. We also discuss the roles of some important genes related to cell apoptosis, DNA repair, drug metabolism, and tumor metastasis in hepatocarcinogenesis related to aflatoxins.
Part of the book: Liver Research and Clinical Management
Aflatoxin B1 (AFB1) is an important carcinogen for primary hepatocellular carcinoma (PHCC). However, the values of blood AFB1-DNA adducts predicting HCC risk and prognosis have not still been clear. We conducted a hospital-based case-control study, consisting of 380 patients with pathologically diagnosed PHCC and 588 controls without any evidence of liver diseases, to elucidate the associations between the amount of AFB1-DNA adducts in the peripheral blood and the risk and outcome of HCC. All subjects had not the history of hepatitis B and C virus infection. AFB1-DNA adducts were tested using enzyme-linked immunosorbent assay. Cases with PHCC featured an increasing blood amount of AFB1-DNA adducts compared with controls (2.01 ± 0.71 vs. 0.98 ± 0.63 μmol/DNA). Increasing adduct amount significantly grew the risk of PHCC [risk values, 1.82 (1.34–2.48) and 3.82 (2.71–5.40) for medium and high adduct level, respectively]. Furthermore, compared with patients with low adduct level, these with medium or high adduct level faced a higher death and tumor-recurrence risk. These results suggest that the blood AFB1-DNA adducts may act as a potential biomarker for predicting the risk and prognosis of PHCC.
Part of the book: Aflatoxin B1 Occurrence, Detection and Toxicological Effects