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Risk Assessment: Science has a hard time gauging the danger posed by carcinogens 

"Genetics loads the gun, environment pulls the trigger"

click to enlarge Testing for toxins in the air and water isn't as thorough as it should be. - PHOTO BY HEATHER MULL

In 1979, after undergoing surgery for bladder cancer, Sandra Steingraber began researching the disease. Steingraber, a college junior majoring in biology, learned that bladder cancer is "a quintessential environmental cancer," strongly linked to exposure to toxic chemicals.

But Steingraber, then 20, hadn't worked in high-risk occupations like textile-dyeing. Nor did she smoke, another risk factor.

Doctors asked about her family history, which was indeed rife with cancer, including the same rare form of bladder cancer she had. But Steingraber is adopted.

Only rarely did anyone suggest potential environmental factors. But eventually her own research revealed, among other things, the presence of bladder carcinogens like the pesticide DDT in the aquifer of her rural Illinois hometown -- and in the sediment of the river nearby. 

Steingraber tells her story in the 1997 book Living Downstream: An Ecologist's Personal Investigation of Cancer and the Environment. Now an activist and scholar-in-residence at Ithaca College, Steingraber acknowledges that some people don't think there's enough evidence to act on environmental toxins. But with some 84,000 synthetic chemicals in circulation, and cancer incidence higher than it was when America's "war on cancer" began 40 years ago, a paucity of evidence is itself a potentially lethal problem. Her book's 2009 edition contends:

 

Our environmental regulatory system requires no rigorous toxicological testing of chemicals [before] marketing them. It promulgates legal limits on [individual] chemical releases, largely overlooking that we are all exposed to trace amounts of many contaminants, and not just one at a time. It is still no one's job to make sure that the total burden of toxic exposures is not too much for any one of us.

 

Unlike Steingraber, many medical professionals shy from discussing potential chemical causes. For instance, in his best-selling 2010 "biography of cancer," the 570-page The Emperor of All Maladies, cancer researcher Siddhartha Mukherhjee devotes just one paragraph to the idea that things like pesticides might help explain the rising incidence of some cancers.

 

Blue Genes

About two in five Americans will get cancer. But for most individual cases, pinpointing a specific cause is impossible. So scientists focus on risks: exposures, behaviors and conditions that increase your odds of getting cancer.

Doctors typically emphasize age -- half the people diagnosed with cancer are 66 or older -- along with genetic susceptibility and personal behavior: smoking, diet, exercise. The risks of obvious occupational exposures (say, among people who've worked with asbestos) are also understood.  

But a growing body of evidence suggests there's more to all this than smoking, genes and where you work.

If cancer were largely genetic, for instance, you'd expect identical twins to develop it at similar rates. But a 2000 study of some 45,000 pairs of Scandinavian twins published in the New England Journal of Medicine concluded that "genetic factors make a minor contribution to susceptibility. … This finding indicates that the environment has the principal role in causing sporadic cancer."

Studies of adoptees like Steingraber, meanwhile, find that incidence of premature cancer death corresponds closely to that of adoptive parents, not birth parents.

"If you look at the chromosomes of identical twins, at age 3, they look pretty much identical," says Devra Davis, the formerly Pittsburgh-based epidemiologist who authored The Secret History of the War on Cancer. But by age 50, "They don't even look like they're related."

Nonetheless, many doctors and scientists still hew to a 1980 study by Richard Doll and Richard Peto. The epidemiologists concluded that no more than 6 percent of cancers came from environmental or occupational exposures, and that "lifestyle" factors like smoking and diet determine most of the rest. 

Doll later upped the environmental-and-occupational figure to as much as 16 percent. Today the National Cancer Institute, citing Doll, says 30 percent of cancers come from smoking, and up to 30 percent from diet, physical inactivity and being overweight or obese.

But some dispute this conventional wisdom. In its surprising 2010 report, for instance, the traditionally conservative President's Cancer Panel asserted: "[T]he true burden of environmentally induced cancer has been grossly underestimated."

 

Playing the Odds

Meanwhile, a newer line of thinking suggests that assigning percentages to causation is itself misleading. Because many influences can damage genes, says Boston University-based public-health expert Richard Clapp, cancer likely results from a web of factors,.

Some are inborn: The body is constantly making cancer cells, scientists have learned, but it usually kills them off. Other factors are environmental, with chemicals accumulating in your tissues. But except in certain (rare) forms of inherited cancer, Clapp and others say, cancer results not from genetics or environment, but in the way they interact. 

"Genetics loads the gun, environment pulls the trigger," Clapp says in a phone interview.

And there's no shortage of potential triggers: In cities like Pittsburgh, the air is full of soot and other cancer-causing chemicals, and all of us harbor traces of pesticides, heavy metals and other toxins. Nearly 300 such synthetics -- more than half known to cause cancer in humans or animals -- can be found even in umbilical-cord blood, according to a 2005 study by the nonprofit Environmental Working Group.

In a 2008 paper, Clapp and his co-authors argue that, in addition to weighing diet and other lifestyle factors, we should "limit exposures to avoidable environmental and occupational carcinogens."

Known carcinogens like arsenic, cadmium and soot are regulated, though we're still exposed to them. That exposure, ideally, is at levels regulators have deemed safe. But excess exposures happen -- as neighbors of U.S. Steel's Clairton Coke Works can attest. 

What's more, there are carcinogens for which there is no known safe level of exposure -- like benzene, which wafts through the air in auto emissions -- and substances whose toxicity remains untold. 

Take the class of chemicals known as hormone mimics, or "endocrine disruptors." Our cells mistake these substances for hormones -- the naturally occurring chemicals that help regulate growth, metabolism and reproduction. Many pesticides and herbicides are endocrine disruptors; other hormone mimics occur in plastics, personal-care products and prescription drugs. One endocrine disruptor, Bisphenol-A -- better known as BPA -- is found in the urine of 90 percent of Americans. 

Endocrine disruptors have been implicated in the discovery of wild animals with abnormal sexual characteristics (like "intersex" fish with eggs in their testes). And tests on lab animals suggest possible links between in-vitro exposure to endocrine disruptors and disorders including testicular cancer.

Manufacturers contend endocrine disruptors like BPA are safe. But alarms are sounding: The President's Cancer Panel report warned of "toxic and hormone-disrupting substances … in maternal blood, placental tissue, and breast milk. … Some chemicals indirectly increase cancer risk by contributing to immune and endocrine dysfunction that can influence the effect of carcinogens."

However, such conclusions are mostly based on animal tests. Under federal law, a chemical must be proved harmful to humans before it can be regulated. And demonstrating danger to humans is surpassingly difficult. Epidemiologists say it's like doing animal studies with the animals let out of their cages: Over their lifespans, your subjects are exposed to countless substances, not just the one you're studying. How do all those chemicals interact? Little is known. There aren't even any control groups -- unexposed populations -- because we're all tainted.

Ultimately, though, Sandra Steingraber has little doubt about where the science points.  In Living Downstream, she imagines a day when we'll view "the deliberate and routine release of chemical carcinogens into the environment as unthinkable as the practice of slavery."

 

Next week: Tackling Toxic Risks

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