FYI Interesting article from Today's NY Times 12/13/2005 Long, but worth it in terms of role of advocacy groups & how scientists stumble across things & finally see a connection they didn't expect. Preventing Cancer Environment and Cancer: The Links Are Elusive By GINA KOLATA When Mike Gallo learned he had cancer, a B cell lymphoma, two years ago, his friends and relatives told him that they knew how he got it. His cancer, Dr. Gallo's friends said, was obviously caused by the dioxin that he had worked with for three decades in his laboratory. After all, the Environmental Protection Agency classifies dioxin as a probable human carcinogen. And among the cancers that it may increase the risk for, in high doses, is lymphoma. Dr. Michael A. Gallo, director of the National Institute for Environmental Health Sciences Center of Excellence at the Robert Wood Johnson Medical School in New Brunswick, N.J., tells his well-meaning advisers that he does not think so. "I say, 'No, I know my blood levels of dioxin,' " Dr. Gallo said, explaining that he measured them when he worked with the chemical. His levels, he said, are low. And there is no way to make a leap from such low levels of dioxin to his cancer. Yet many of his friends and relatives remain convinced. "That's the way people think," Dr. Gallo said. "If you get cancer, there has to be a reason." And there may be a reason, he and other scientists say. But pinning cancer on trace levels of poisons in the environment or even in the workplace is turning out to be a vexing task. There has been recent progress in addressing the issue, but the answers that many people believe must be out there remain elusive. "It's an area where there's certainly been a lot of heat and not a lot of light for some time," said Robert Hoover, director of the epidemiology and biostatistics program at the National Cancer Institute. For the most part, Dr. Hoover said, "we are down to speculations based on some data but without having the information we need." Members of advocacy groups agree that there is much to learn, but they say the questions are too important to brush off by saying the research is difficult or the questions complex. "Science is very specific," said Linda Gillick, a founder of Ocean of Love, a support group for children with cancer in Ocean County, N.J. "Sometimes you have to think outside the box." Barbara Brenner, executive director of the Breast Cancer Action Coalition, an advocacy group in San Francisco, said that at the very least people should look for the least toxic alternative to chemicals in common use that may cause cancer. Having had breast cancer twice, Ms. Brenner is impassioned by the cause. "I have a firsthand experience, and I would do anything - anything - to keep someone else from having that experience," she said. Researchers, for their part, say they have not given up the quest. In their search for answers, they are trying a variety of methods. They are looking for reliable ways to detect environmental exposures and determine whether they are linked to cancer risk. They are studying the bewildering array of factors that can determine a chemical's effects on individual people. And they are looking at cancer statistics and asking whether there are blips in cancer rates that may point to an environmental cause. The effort is important, Dr. Hoover said. While most scientists think that only a tiny fraction of cancers might be caused by low levels of environmental poisons, these are cancers that could, in theory, be avoided. "All it takes is the political will to ban them or impose regulations to minimize exposure, and the cancers are gone," Dr. Hoover said. The problem is to decide which chemicals might be causing cancer, and in whom. Some scientists, like Aaron Blair, an epidemiologist at the National Cancer Institute, see hints that environmental pollutants like pesticides, diesel exhaust in cities and workplaces and small particles in the air may instigate cancer. But, Dr. Blair says, there is a huge problem in following up on these hints because scientists need to figure out who was exposed to what and when the exposure occurred. Asking people is not much help. Most people do not know what they were exposed to, and even if they think they know, they often are wrong, he said. So Dr. Blair and his colleagues decided to try for the greatest possible rigor by focusing on one group, farmers, that is not only routinely exposed to pesticides that may increase cancer risk, but also keeps excellent records of exposure. The effort, a collaboration involving the cancer institute, the National Institute of Environmental Health Sciences and the Environmental Protection Agency, began in 1993 and includes nearly every farmer and farmer's spouse in Iowa and North Carolina - 55,000 farmers and 35,000 spouses. Investigators have been asking the farmers what pesticides and herbicides they used, when they used them and how much they used, and have been obtaining information on other risk factors like smoking. Then they use the medical records from tumor registries to determine who developed cancer and what type was developed. "We're now just in the period of time where we can look at outcomes," Dr. Blair said. So far, the researchers have found a few associations, but nothing that is definitive. "I would call it, at this stage, interesting leads," Dr. Blair said. "None are large enough for any regulatory agency to take action or to say they are a human carcinogen. They are leads." They include, for example, a slightly higher rate of lung cancer and leukemia in farmers who used the insecticide diazinon and a possible increase in prostate cancer among farmers who used methylbromide to fumigate the soil. The investigators looked for an association between pesticides and herbicides and breast cancer, but they did not find one, Dr. Blair said, adding that one pesticide, atrazine, was under particular suspicion because it causes breast cancer in rats and has estrogenlike properties. Even if the study finds that some chemicals have increased farmers' cancer rates, it remains unclear what that means for the general population, where exposures are usually much lower. Also unclear is whether those chemicals should be banned. Dr. Blair noted that such decisions were difficult because they were, in part, political, balancing the costs of getting rid of the chemical against the benefits. But, he said, regulatory decisions require reliable scientific data. "You can only make a decision if you know something," he said. So the studies continue. "We want to know what to worry about, so at least we can make rational decisions," Dr. Blair said. Gerald N. Wogan, a chemist at the Massachusetts Institute of Technology, takes a different approach. He, like most other scientists, worries that the public is overly concerned about cancer risks from the chemicals they are exposed to. But, he says, the question of how environmentally induced cancers arise is a puzzle that he would like to solve. Dr. Wogan became interested in pollutants and cancer when he began studying the effects of aflatoxin, produced by mold on peanuts. The toxin caused liver cancer in rats and, Dr. Wogan and others showed, it also causes liver cancer in people. But exposure to aflatoxin was just part of the risk. Dr. Wogan studied men in Shanghai who were eating foods with high doses of the toxic chemical. They ended up with four times the risk of liver cancer. Another cause of liver cancer, hepatitis B infections of the liver, increases the risk by a factor of seven. Then Dr. Wogan noticed something that astonished him. The risk of liver cancer was increased 70 times in people who met both criteria; they ate contaminated foods and they were infected with hepatitis B. "It was like a model system for the environmental causes of cancer," Dr. Wogan said. The two cancer-causing agents were amplifying each other's effects. He went on to study the mechanisms of cancer causation and discovered that the more he looked at environmental pollutants the more complex and individualistic the biochemical pathways leading to cancer turned out to be. "People differ very greatly in their response to chemical carcinogens," Dr. Wogan said. "Almost all chemicals, with relatively few exceptions, have to be converted from what they are into something more chemically active to be carcinogenic. "If you encounter one of these compounds, most of it is converted to less toxic material that is excreted," he continued. "Only a tiny amount is converted to a form that could cause cancer. A small fraction of 1 percent gets converted. And people can differ enormously in their genetic ability to do these metabolic conversions." Further complicating the issue is that a person's diet, or components of the diet, can increase the activity of enzymes that convert chemicals into carcinogens. And other dietary components can inactivate enzymes that detoxify chemicals. The calculus grows so complex that it can be virtually impossible to predict what will happen in an individual person exposed to low levels of a possibly toxic chemical. For example, Dr. Wogan said, "The same food, broccoli, can affect both types of enzymes." Added to this are the effects of chronic infections, like hepatitis B, in which the immune system releases chemicals that can magnify the effects of carcinogens. In theory, Dr. Wogan said, there is hope for untangling the mess. "If we knew how to identify exactly which factors or agents or dietary factors were responsible and if we were able to identify their effects in people, then, in principle, cancer is preventable," he said. But, he added: "It's so tough. It's so very tough to do." In the meantime, he and others say they take comfort in cancer statistics that do not indicate a cancer epidemic. Rates of cancer have been steadily dropping for 50 years, if tobacco-related cancers are taken out of the equation, said Prof. Richard Peto, an epidemiologist and a biostatistician at Oxford University. What appear as increases in cancers of the breast and prostate, Dr. Peto added, are in fact artifacts of increased screening. When healthy people are screened, the tests find not only cancers that would be deadly if untreated, but also a certain percentage of tumors that would never cause problems if let alone. His analysis of cancer statistics leads Dr. Peto to this firm conclusion: "Pollution is not a major determinant of U.S. cancer rates." Advocates for cancer patients, like Ms. Gillick, of Toms River, N.J., do not agree. They say they have heard it all - scientists' insistence that the risk of cancer from environmental chemicals is very low, that it is almost impossible to ascribe cancer in any individual to an environmental exposure, that most cancers are just a result of unlikely genetic draw or spurious mutation. But Ms. Gillick and other advocates are not convinced. Her son Michael, 26, was given a diagnosis of neuroblastoma when he was 3 months old. Ms. Gillick had never heard of that cancer, a pediatric cancer of the sympathetic nervous system. But she soon learned how devastating it could be. Over the years, as Michael spent time in hospitals in New York and Philadelphia, she noticed something striking. Child after child in those cancer wards came from her town and surrounding Ocean County. "You start talking to the other parents," Ms. Gillick said. " 'Why? How could that have happened?' " She found what she thought was the answer: trace levels of industrial chemicals in the drinking water. But the cancer institute and the E.P.A. investigated and said that they saw no particular danger in the water and that what looked like an increase in childhood cancer was just a statistical fluke. Dr. Gallo was sent to talk to Toms River residents. Although Ms. Gillick said that she respected him and his views and that she found him likable, she did not like his message. "Scientists," Ms. Gillick said. "They think it was random bad luck or whatever. "We can't sit back and say, 'O.K., it happened.' If we could find the cause of a lot of these cancers, we wouldn't have to worry about the cure." That is also the message of the Breast Cancer Action Coalition. "We think there is something going on, and we'd like to find out what it is," said Ms. Brenner, the executive director. "The scientists who say these kinds of environmental exposure are the smallest contributors, I'd like to know how they know that. If we haven't done the research, how can they say with assurance what is the contributor to anything?" And, she adds, there are now so many chemicals in the environment that the task of figuring out what effects they might have is dizzying. "Nobody can keep up," Ms. Brenner said. "And we don't know the health effects. I think it is not an irrational response to say our environment is making us sick." That is not Dr. Gallo's view. Even though he had cancer, he is not blaming environmental exposures. "If I were to take that tumor that came out of me and grind it up and run it through a mass spectrometer, I could find every persistent organic chemical I've ever been exposed to," he said. "Is that cause and effect? No, it's an association." Still, he understands the concerns. "We, the scientific community, should take the blame for this," Dr. Gallo said. "Toxicologists, and I'm one of them, have perpetuated the idea that if 100 molecules are going to kill you, then one molecule is going to kill 1 percent of somebody. And that's the problem. We have a tremendous ability to analyze anything and everything, and the scientific community has said: 'Oh, by the way, we ran this chemical in rodents and found cancer. And therefore ... .' " Dr. Gallo added that cancer was a complex disease. "There is a gene and environment interaction, and the environment is much broader than just chemicals," he said. "The challenge is to figure out what is the role of the gene and how does the lifestyle and environment overlay that gene." And science, he said, is just not there yet.