A Call For More Research On Cancer's Environmental Triggers

Jul 12, 2019

We already know how to stop many cancers before they start, scientists say. But there's a lot more work to be done.

"Around half of cancers could be prevented," said Christopher Wild in the opening session of an international scientific meeting on cancer's environmental causes held in June. Wild is the former director of the World Health Organization's International Agency for Research on Cancer.

"Cancer biology and treatment is where most of the money goes," he said, but prevention warrants greater attention. "I'm not saying that we shouldn't work to improve treatment, but we haven't balanced it properly."

Perhaps no question about cancer is more contentious than its causes. People wonder, and scientists debate, if most malignancies stem from random DNA mutations and other chance events or from exposure to carcinogens, or from behaviors that might be avoided.

At the conference in Charlotte, N.C., scientists pressed for a reassessment of the role of environmental exposures by applying modern molecular techniques to toxicology. They called for more aggressive collection of examples of human pathology and environmental samples, including water and air, so that cellular responses to chemicals can be elucidated.

The hope is that by identifying specific traces of exposures in human cancer specimens, scientists can identify environmental causes of disease that might be prevented.

"Over 80,000 chemicals are used in the United States, but only a few have been tested for carcinogenic activity," said Margaret Kripke, an immunologist and professor emeritus at MD Anderson Cancer Center, in an interview at the meeting.

"This has been a very neglected area of cancer research for the last several decades," said Kripke, the driving force behind the conference, which was put on by the American Association for Cancer Research. "Environmental toxicology was very popular in the 1950s and 1960s," she said, but genetics then began to overshadow studies of cancer's environmental causes. "Toxicology fell by the wayside."

While the incidence of tobacco-linked cancers has been falling, malignancies not associated with smoking are rising, Kripke said. Recent evidence suggests an escalating rate of lung cancer in nonsmokers. That trend implicates other environmental factors.

Around the globe, cancer's overall incidence is climbing. This year, 18 million people will be diagnosed with some form of cancer and over 9 million will die from it.

Infections — many preventable, such as by human papillomavirus —account for 15% of new cases.

Another rising cause is obesity, along with urbanization. People generally get less physical activity and eat differently in cities, and pollution is heavier there, too. "As people move into cities, that will drive up cancer rates," Wild said.

One of the biggest obstacles to preventing cancer is that many people just don't think it's feasible. Progress "requires long-term vision and commitment," Wild said. "Funding is limited, and there's little private sector investment."

A change in the way benefits of cancer prevention are framed could help. "When I was at the IARC, one thing that struck me was the power of economic arguments over health arguments for preventing cancer," Wild said.

Cancer treatment costs can be prohibitive. But productivity lost from premature deaths in Brazil, Russia, India, China and South Africa alone runs $46.3 Abillion annually, he said. "Developing countries are not prepared to deal with the rising cancer burden."

The precise proportion of cancers arising from environmental and occupational exposure to carcinogens is uncertain. In 2009, a report by the President's Cancer Panel called prior approximations of around 6% "woefully out of date" and low. A 2015 paper by over a hundred concerned scientists cited "credible" estimates of 7% to 19%.

Scientist at the Charlotte meeting emphasized the complexity of cancer's causes and the need for toxicologists to update methods to reflect that complexity, such as by studying interactions of environmental and genetic risks, and by examining cells after a mix of exposures. "Most toxic exposures do not occur singly," said Rick Woychik, deputy director of the National Institute of Environmental Health Sciences.

Until recently, many toxicology tests were performed in rodents, because it would be unethical to deliberately evaluate possible carcinogens in people. But these animal experiments are labor-intensive and slow, he said.

New alternatives are now being tried. "We learned from pharma that with robotics and high-throughput technology you can interrogate a lot of biology quickly and at lower costs," he said.

Epidemiological research of human exposures has been stymied by the difficulty of proving cause-and-effect — that a particular substance actually causes cancer — and by shortcomings of survey data from questionnaires.

At the conference, scientists offered glimpses of new technology that is helping fill informational gaps.

Bogdan Fedeles of MIT explained how DNA serves as a lifelong "recording device." He and others use duplex sequencing to examine human samples for genetic "fingerprints of exposure."

Allan Balmain, a geneticist at University of California, San Francisco, spoke about mutational signatures in malignancies. In liver cancer, for instance, these signatures can offer causal clues—such as smoking, alcohol or aflatoxin, a product of mold that grows on some foods.

Many chemicals that cause or stimulate cancer growth are produced inside our bodies. "It's not all about the environment," Balmain said.

Others highlighted a conceptual shift in how scientists define carcinogens. Key characteristics may include a substance's capacity to stimulate growth of malignant cells, or to induce inflammation—without necessarily causing DNA damage, long seen as the necessary .

"The answer to 'What is a carcinogen?' is changing" said Ruthann Rudel, a toxicologist at the Silent Spring Institute who has published extensively on breast carcinogens. She detailed new techniques to screen breast cancer cells for changes in response to specific chemical exposures.

The public health stakes for the field are high.

Professor Polly Hoppin, of the University of Massachusetts, Lowell, discussed cancer-causing industrial contamination of drinking water at Camp Lejune, N.C., air pollution in St. John the Baptist Parish, La., and potential exposures to carcinogens from fracking and planned plastics production in Pennsylvania.

Hoppin reflected on the U.S. experience with tobacco cessation. Scientists knew that smoking causes cancer by the 1950s, she said. Implementing that knowledge required policy and incentives — like high cigarette taxes and public smoking bans — and took decades.

"The science wasn't enough," Hoppin said. "How many lives could have been saved if we'd acted sooner?"

Elaine Schattner is a physician in New York writing a book on cancer attitudes that will be published by Columbia University Press.

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