Preventing Liver Cancer in Qidong, China: Science Meets Serendipity

Issue 21, Summer/Fall 2013

SOMEONE SHOULD STAND UP AND TAKE A BOW. BUT WHO?

Success in primary cancer prevention requires the sustained efforts of many individuals over long periods of time, and is the result of intersecting strategies of science, public policy and, sometimes, serendipity.

Here in the United States, we are 50 years on from the landmark Surgeon General's report, and decades further still from key studies that first linked the post-WWII increase in lung cancer to widespread addiction to cigarettes. And now? Lung cancer mortality is dropping in the U.S., and overall smoking rates in the U.S. are at about 19 percent, down from 42 percent in the mid-1960s.

In another success story, stomach cancer mortality has dropped from being the number one cancer killer of Americans in 1900 to dropping off of the top 10 list today. Here we don't know why. Perhaps changes in our diet, how our foods are processed, or the increased use of antibiotics and consequent diminution of infections with Helicobacter pylori all play roles. Huge changes, but nobody takes a bow.

Now, another killer cancer is on the wane in eastern China. In the region of Qidong, a peninsula formed from deposits by the Yangtse River that juts into the East China Sea north of Shanghai, liver cancer has been the number one cancer killer for the past 50 years. In some of the rural farm villages of Qidong, upwards of one in ten adults die of liver cancer, and more Qidongese died of liver cancer last year than in any previous year, in part because the population is getting older.

And yet there has been a spectacular and increasing drop in liver cancer mortality amongst younger Qidongese who were born in the 1970s and later. In fact, the age-standardized rate has dropped by nearly 50 percent. What has changed?

A Virus and a Staple Food

We know the key risk factors for liver cancer in this region: infection with hepatitis B virus (HBV) and exposure to liver carcinogens in the diet, in particular, fungal-borne carcinogens called aflatoxins. Experts know that a key tenet of public health is primary prevention -- elimination or reduction of the risk factors. So, what has been done to bring about the decline in liver cancer deaths?

Farm in Qidong

Vaccination against hepatitis B virus has been near universal in the United States since the mid-1980s, but free and universal vaccination of newborns only became mandated in China in 2004.

Access to the vaccine, especially in the rural areas, was quite limited prior to the past decade. Now, newborns are targeted for vaccination because transmission of the virus often occurs from mother to child during the perinatal period. Once a person is infected, the vaccine has little effect.

However, since so little time has passed since the initiation of vaccination and because very few of those Qidongese who are currently dying from liver cancer were ever vaccinated (their median age is late 40s to early 50s), the introduction of the HBV vaccine cannot be the answer. Not yet anyway. For certain, global vaccination against HBV will have a huge impact in a generation or so, but we'll have to delay that bow for now.

So, what about aflatoxins? Humans are exposed to aflatoxins by consumption of commodities such as corn, peanuts and sorghum that are contaminated by fungi during growth, harvest or storage. The new land forming Qidong has never been suitable for growing rice, the dietary staple of much of China.

Instead, most Qidongese grew and ate corn (maize) during the 1960s to mid- 1980s. In the commune system of China at that time, "grow local, eat local" had a different meaning than it does today. Farming units had to meet production quotas, and there was zero incentive for food quality. That meant that the maize in Qidong was often contaminated with aflatoxins.

Reports from the 1970s indicate that between 25 and 99 percent of the maize from annual surveys had levels that would exceed the limits imposed by the US Food and Drug Administration for aflatoxin contamination of corn produced in the U.S. Rice was grown south of the Yangtze River but could not be imported into Qidong.

But then something changed. In the mid-1980s came the reforms of Deng Xiaoping and the development of a limited market economy, coupled with the dissolution of communes. Chinese agriculture morphed quickly from a command and control system to a largely free-market sector.

Corn in Qidong

From Corn to Rice

Today, corn continues to grow in Qidong, but is used as animal feed, and the Chinese staple rice is imported from neighboring areas for human consumption. So by 1985, rice had become the dominant foodstuff in Qidong.

This change in food had an enormous effect on liver cancer, because while maize is consistently contaminated with aflatoxin -- especially in hot, humid environs such as Qidong -- such is rarely the case for rice.

In order to reconstruct exposures, we have recently completed a retrospective analysis of aflatoxin "biomarkers" (aflatoxin bound to the blood protein albumin) in archived blood samples from our studies in Qidong over the past three decades. We have observed a greater than 40-fold drop in biomarker levels from the samples of the 1980s to the present. Indeed, in samples collected this past fall, nearly all had undetectable levels.

So, it appears that the dramatic, draconian change in economic/agricultural policy has led to a serendipitous elimination of a key risk factor for liver cancer in this region. This is yet another proof-of-principle example that eliminating exposure to a human carcinogen makes a big difference in cancer rates. And now that HBV vaccination has gained a foothold, it can be hoped that by the mid-century liver cancer will be just a footnote to the health of Qidongese.

Still, it's important to remember that liver cancer remains the third leading cancer killer worldwide. HBV and aflatoxin may not always be to blame, but they certainly exert their nefarious effects.

So, take a bow Qidong -- on behalf of serendipity, you've shown what can be done. But stuff out those cigarettes, because lung cancer is the new number one cancer in your region, and we already know what works on that score.

Thomas Kensler, PhD

Thomas Kensler, PhD
For the Qidong Liver Cancer Study Team

Professor
Environmental Health Services
Johns Hopkins Bloomberg School of Public Health
Baltimore, MD