Population attributable risk of aflatoxin-related liver cancer: Systematic review and meta-analysis

Abstract

Background Over 4 billion people worldwide are exposed to dietary aflatoxins, which cause liver cancer (hepatocellular carcinoma, HCC) in humans. However, the population attributable risk (PAR) of aflatoxin-related HCC remains unclear. Methods In our systematic review and meta-analysis of epidemiological studies, summary odds ratios (ORs) of aflatoxin-related HCC with 95% confidence intervals were calculated in HBV+ and HBV− individuals, as well as the general population. We calculated the PAR of aflatoxin-related HCC for each study as well as the combined studies, accounting for HBV status. Results 17 studies with 1680 HCC cases and 3052 controls were identified from 479 articles. All eligible studies were conducted in China, Taiwan, or sub-Saharan Africa. The PAR of aflatoxin-related HCC was estimated at 17% (14–19%) overall, and higher in HBV+ (21%) than HBV− (8.8%) populations. If the one study that contributed most to heterogeneity in the analysis is excluded, the summarized OR of HCC with 95% CI is 73.0 (36.0–148.3) from the combined effects of aflatoxin and HBV, 11.3 (6.75–18.9) from HBV only, and 6.37 (3.74–10.86) from aflatoxin only. The PAR of aflatoxin-related HCC increases to 23% (21–24%). The PAR has decreased over time in certain Taiwanese and Chinese populations. Conclusions In high exposure areas, aflatoxin multiplicatively interacts with HBV to induce HCC; reducing aflatoxin exposure to non-detectable levels could reduce HCC cases in high-risk areas by about 23%. The decreasing PAR of aflatoxin-related HCC reflects the benefits of public health interventions to reduce aflatoxin and HBV.

Hepatocellular carcinoma and the risk of occupational exposure

“…Chronic exposure causes the development of liver cancer. This could be caused by the aflatoxin ability to determine the mutation of the p53 tumor suppressor gene, which in normal conditions induces the apoptosis processes [74][75][76][77] . The risk of HCC increases when the exposure occurs in the presence of HBV infection, as occurs in the Chinese population [78][79][80][81][82][83][84][85][86][87][88][89][90][91][92][93][94][95][96] .…”

Contributions of polymorphisms in miR146a, miR196a, and miR499 to the development of hepatocellular carcinoma

“…More than 80% of cases occur in developing countries, with half arising in China (International Agency for Research on Cancer, 2012). The etiology of the disease has been widely studied, and previous research has demonstrated that many environmental and lifestyle factors, such as hepatitis B/C virus infection, aflatoxins, long-term alcohol consumption and liver cirrhosis (Nguyen et al, 2009;Liu et al, 2012;Niu et al, 2016). Previous studies have demonstrated that many genetic variations contribute to the risk of developing hepatocellular carcinoma, including C-reactive protein, Holliday junction recognition protein (HJURP), epidermal growth factor 61A/G, and Ghrelin and FasL genes (Lao et al, 2015;Shen et al, 2015b;Zhang et al, 2015a;Huang et al, 2016;Khalifa et al, 2016).…”

Perspective: Time to face the fungal threat

“…People whose livers are already compromised by infection with hepatitis B virus (HBV) are particularly susceptible to aflatoxininduced liver cancer 3 . Studies by my team 1,2 suggest that up to 172,000 cases of HCC per year can be attributed to exposure to aflatoxin in the diet, and most of these individuals are infected with HBV. The majority of cases occur in sub-Saharan Africa, southeast Asia and the western Pacific region (including China), as well as in parts of Central America.…”