Profound primary prevention of liver cancer following a natural experiment in China: A 50‐year perspective and public health implications

Liver cancer causes upwards of 1 million cancer deaths annually and is projected to rise by at least 55% over the next 15 years. Two of the major risk factors contributing to liver cancer have been well documented by multiple epidemiologic studies and the hepatitis B virus (HBV) and aflatoxin show a synergy that increases by more than 8‐fold the risk of liver cancer relative to HBV alone. Using the population‐based cancer registry established by the Qidong Liver Cancer Institute in 1972 and aflatoxin‐specific biomarkers, we document that reduction of aflatoxin exposure has likely contributed to a nearly 70% decline in age‐standardized liver cancer incidence over the past 30 years despite an unchanging prevalence of HBV infection in cases. A natural experiment of economic reform in the 1980s drove a rapid switch from consumption of heavily contaminated corn to minimally, if any, contaminated rice and subsequent dietary diversity. Aflatoxin consumption appears to accelerate the time to liver cancer diagnosis; lowering exposure to this carcinogen adds years of life before a cancer diagnosis. Thus, in 1990 the median age of diagnosis was 48 years, while increasing to 67 years by 2021. These findings have important translational public health implications since up to 5 billion people worldwide might be routinely exposed to dietary aflatoxin, especially in societies using corn as the staple food. Interventions against aflatoxin are an achievable outcome leading to a reduction in liver cancer incidence and years of delay of its nearly always fatal diagnosis. What's new? Relative to hepatitis B virus (HBV) alone, combined infection with HBV and aflatoxin B1 is associated with an 8‐fold increase in liver cancer risk. Here, these two factors were assessed for temporal impacts on liver cancer incidence in Qidong, China, where exposure rates to aflatoxin and HBV have shifted significantly. Analyses suggest that the transition from corn to rice consumption in Qidong, driven by economic reform in the 1980s, contributed to a 250‐fold reduction in serum aflatoxin biomarkers. This reduction was linked to a marked decline in liver cancer incidence and an increase in median age at diagnosis since 1990.