Aflatoxins are produced by the fungi Aspergillus flavus and Aspergillus parasiticus and are common food contaminants in tropical developing countries. Extensive aflatoxin consumption has been shown to be highly associated with liver disease. A case-control study was conducted to determine the association between aflatoxin and liver disease in Kumasi, Ghana. A questionnaire was administered to examine socio-demographic characteristics and food storage and consumption practices, and urine samples were collected to measure levels of the aflatoxin metabolite (AFM1). Two hundred and seventy-six people participated in the study; 38 had liver disease (cases), 136 had neither hepatitis B/C nor liver disease (negative controls), and 102 were hepatitis B/C positive without liver cancer (positive controls). A much higher percent of participants in each group was male (76% of cases, 88% of negative controls and 65% of positive controls). Multivariate analysis showed that age was a significant predictor for being a case when cases were compared to negative controls. The odds of being a case was 70% less for participants aged 25–34 years (odds ratios (OR) 0.30; 95% confidence interval (CI) 0.10–0.88) compared to those ≥45 years. For cases; Akans were seven times more likely to have AFM1 levels below the median when compared to other ethnic groups (OR 7; CI 1.41–34.68). When cases were compared to positive controls, they were 2.29 times more likely to report awareness of aflatoxin contamination of groundnuts (95% CI 1.06–4.91). Cases were also two times more likely to report awareness of aflatoxin contamination of maize than all controls combined (95% CI 1.02–4.11). However, most cases reported that aflatoxin contamination does not cause sickness in humans. This shows that there is awareness of aflatoxin contamination without proper understanding of the serious potential adverse health impacts among these study participants. These findings indicate that educational interventions that stress the harmful health effects of aflatoxin in food, with an emphasis on the higher risk for males, are urgently needed. The reasons for lower aflatoxin levels among Akans need to be determined, and the findings used to design interventions that benefit other ethnic groups in the society.
Nuclear receptor subfamily 4 group A member 2 (NR4A2) is an orphan nuclear receptor that is over-expressed in cancer and promotes cell proliferation, migration, transformation and chemoresistance. Increased expression and function of NR4A2 have been attributed to various signaling pathways, but little is known about microRNA (miRNA) regulation of NR4A2 in cancer. To investigate the posttranscriptional regulation of NR4A2, we used a 3′ untranslated region (UTR) reporter screen and identified miR-34 as a putative regulator of NR4A2. By using computer predictions, we identified and confirmed an miRNA recognition element in the 3′ UTR of NR4A2 that was responsible for miR-34–mediated suppression. We next demonstrated that overexpression of exogenous miR-34 or activation of the p53 pathway, which regulates endogenous miR-34 expression, decreased NR4A2 expression. Consistent with previous reports, overexpression of NR4A2 blocked the induction of p53 target genes, including mir-34a. This was a phenotypic effect, as NR4A2 overexpression could rescue cells from p53-induced inhibition of proliferation. In summary, our results are the first characterization of a cancer-related miRNA capable of regulating NR4A2 and suggest a network and possible feedback mechanism involving p53, miR-34 and NR4A2.