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MEDICI ! . ; v' s ' *C>-JrVfX;"* . "j-'jj "'V'w;', ) A' 'fr'v#*v"'?^pAi L mericans used to think of can cer--when they permitted themselves to think of it at all-- Las one of those roll-of-the-dice diseases: mysterious, unpredictable and, if your number came up, unavoidably fatal. But recently, they have been learn ing something new and, in a sense, far more frightening about cancer. In the vast majority of cases, cancer may be a man-made disease. To judge from newspapers, magazines and television, even the simple acts of eating, drinking, breathing and touching may expose Americans1 to some possible cause of cancer. Women have been warned not to eat beef liver because it may produce cancer ofthe vagina. Sever al of the nation's major sources of water have been found to contain an industrial chemical that causes cancer in laboratory rats. Polyvinyl chloride (PVC), a plastic used in food wrapping, is also under suspicion. Some housewives began to shun bacon and ham after they were told these products contain dangerous "the introduction into the universe of potent chemical agents which are largely untested for adverse public-health ef fects." Epstein notes that cancer rates have nearly tripled since 1900 (partly because of increased life expectancy, partly because of better diagnostic tech niques), and that they have gone up 1 per cent a year since 1933--not to mention the mysterious but still tentativeJ3.8 per cent increase indicated for 1975. "There is no question," he says, "that cancer is a major epidemic." Though a number of Epstein's col leagues might choose to state the case less dramatically, few disagree that the environment and what man has done to it loam increasingly as the major sources of the second greatest killer (after heart attacks) in the nation. In coincidental support of this thesis. Academic Press this week will publish a massive, 544page report entitled "Persons at High Risk of Cancer." Based on a symposium sponsored by the National Cancer Insti tute and the American Cancer Society, ymfc. Figures indicatepercehtageahj estimated T976 'cancer deaths- chemicals. Perhaps most worrisome of all is the fact that the latest statistics show a cancer-death rise of 3.8 per cent for 1975--though this may be revised when all the figures are in. Small wonder, then, that many scien tific experts have begun to regard the environment--everything we come into contact with--as a far more significant source of cancer than aberrant cellular mutation. Even if the headlines tend sometimes to overstate the case, there seems little doubt that the newest fron tier in cancer research has now become the environment itself. Already the World Health Organization estimates that up to 85 per cent of all cancer cases are the direct result of exposure to envi ronmental factors of one kind or an other--in many instances almost fatalis tically self-inflicted by such habits as overeating, smoking, overdrinking and excessive exposure to sunlight and dan gerous chemicals in the factories- Some scientists, Tike Dr. Samuel S, Epstein, an environmental toxicologist at Case Western Reserve University Medical School, think that the past two or three decades have witnessed a phe nomenon unique in the history of man-- the report offers a sweeping and meticu lously documented appraisal ofthe most recent research on the epidemiology of cancer in man--with special emphasis on the possible roles of diet, drugs, radiation and the workplace. lready, the concern about the role of the environment in cancer seems to presage a major shift in the application of cancer research funds. Critics charge that the NCI has so far failed to devote an appropriate slice ofits $690 mil lion budget to research on cancer control and prevention and on the identi fication of carcinogens in the environ ment. They say that NCI researchers are spending an inordinate amount on basic research, including $90 million on a virus program that has yet to uncover a humancancer vims. The critics charge that even if such a virus is found, it would account for only a small number ofcancer cases. Of the remaining $600 million in die NCI budget, only $45 million will go this year into research on carcinogens. But even this sum represents a new empha sis on cancer prevention. Only $7 million 62 RSV0024787 1 Newsweek was devoted to such projects a few years ago. And eventually, NCI plans to spend an additional S50 million on a program to study the role of diet alone in cancer. Last summer, NCI published a "Cancer Atlas" based on a survey ofcancer deaths in the 3,056 counties ofthe contiguous 48 states. "It's generating a lot of ideas of where to look and what to do," says Marvin Schneiderman of NCI. Among the patterns emerging from the cancer map (page 67) were the high rates of bladder cancer in the industrialized Northeast as well as excessive lung and liver cancer rates in smelting-industry communities. In recent months, the search for can cer-causing substances in the environ ment has stirred a welter of controversy, involving environmentalists, industry and the scientists themselves. Even the experts disagree somewhat on what sub stances are hazardous and what ought to be done about them when they are found. Of more than 1,400 chemicals, drugs and pollutants now suspected of causing cancer--mostly on the basis of animal tests--only about 22 are now widely held to be carcinogenic to man. amounts in the last 30 years to make polyvinyl chloride, a plastic found in a vast array of items, including food con tainers and phonograph records. In 1973, Italian reseachers found that VC pro duced liver tumors in rats. The findings were largely ignored until it was learned that the same kind of tumor--exceeding ly rare under ordinary circumstances-- had taken the lives of three workers at the B.F. Goodrich plant in Louisville, Ky. Only then were revised standards on exposure put into effect. ^or the scientists, there are two major problems in uncovering cancercausing substances. The first is the long "latent" period--often twenty to 35 years--between the beginning of expo sure to a carcinogenic substance and the appearance of malignant disease. In ad dition, scientists find themselves in dis agreement on how big a dose of a substance is enough to trigger cancer. Some researchers point out that almost anything, including sugar and salt, will cause trouble if given in a large enough Responsibility for protecting the pub lic from carcinogens is shared by a bu reaucratic web of government agencies that includes the Environmental Protec tion Agency, the National Institute for Occupational Safety and Health, the Occupational Safety and Health Admin istration and the U.S. Food and Drug Administration. Not surprisingly, their responsibilities not only overlap but are often in direct conflict, with different agencies setting different standards for regulating suspect chemicals. Most experts agree on the need for a law that would mandate testing of all new chemicals and drugs for toxicity-- including the tendency to cause can cer--before, not after, they enter the environment. "If you wait till people are hit by the epidemic," says the NCI's Dr. Umberto Saffiotti, "it's too late." Such a bill has lain before Congress for five years, and pianyeritics charge it has been blockedby Industry pressure. 'The consumensts point to the recent vinyl-chloride episode as a stark exam ple of the failure of the present system to catch a dangerous chemical before it causes trouble. Vinyl chloride is a gas that has been used in ever-increasing dose. Most regulations are based on the idea that there is a "threshold" of expo sure, below which there is no risk. But many experts insist there is no such thing as a safe level. "Lower concentrations simply mean lower incidence," says Ep stein. "There is no threshold." The second and equally controversial question is whether testing in animals is a reliable indicator of what a substance will do to man. The amount of a sub stance required to cause cancer in an an imal may not realistically reflect the amount that humans can safely be ex posed to. But toxicologist Epstein insists thatanimal results are applicable to man. "Information in tests from well-designed and valid animal systems," he says, "con stitutes very strong evidence for a cancer hazard in humans." Some manufacturers have been sus pected of hiding or falsifying test results indicating a cancer hazard.. Last week, Newsweek learned,' thA EPAiand the Department of Health;rEdueah'on and Welfare were thinking of taking criminal action against several corporations and commercial testing labs for just such fraud. The agencies are also planning to look into conflict-of-interest charges in- January 26, 1976 Photos by iTftnivs Mei-nughlm-Gifi RSV0024788 scientists who act as paid advis ers to regulatory agencies while getting consultant fees from private companies. Workers who have been exposed to carcinogens in theirjobs are often amaz ingly philosophical about the lifethreatening risk they are taking. Charles Russell of New York has been inhaling asbestos fibers for 28 years as an insula tion worker. Now, he turns up regularly at his union headquarters for lung-cancer checkups conducted by Dr. Irving SelikoffofNew York's Mount Sinai Hospital, who was among the first to show that asbestos workers exhibit a high propen sity for the disease. "It's a bad risk," says Russell, who is healthy so far, "but where are you going to find work? I'm taking home $230 a week, so what can you do?" Clearly, the environment is never go ing to be entirely free ofcarcinogens, and the government, researchers and con sumers have to make practical choices about the risks they are willing to take. "Before eliminating pesticides like DDT," says E. Cuyler Hammond, chief of epidemiology for the American Can cer Society, "you must carefully consider what it might mean for the health and nutrition ofmuch ofthe world." The outcry that follows each succesBve new disclosure ofa possible carcino- on the dinner table or in the work shop tends to obscure the fact that 60 million Americans continue to expose themselves to tobacco--the least disput ed carcinogen of all. Moreover, many experts believe the problem has been exploited to an unconscionable degree by some overzealous consumers, organic-food promoters and the news media. "American cancerophobia," noted a recent editorial in the prestigious New England Journal of Medicine, "is a disease as serious to society as cancer is to the individual." The truth is that cancer is not one disease, but at least 100 separate dis eases involving a derangement in the fife of the body's cells. Only by studying the epidemiology of cancer in humans on a vast scale can the effect of life-style on the disease be determined. Following are some of the most important and promising clues on the questions of environment and cancer, taken from the just-published "Persons at High Risk of Cancer" and interviews by Newsweek reporters: 1. FOOD AND DRINK Tony Hutto--Neuwrtek Food: In an affluent society, the better fed may be worse off themselves, they combine with amines (chemical com pounds derived from ammo nia) found in the body to form nitrosamines. And nitrosamines are highly potent car cinogens in animals. Several epidemiologists have tied nitrates in smoked fish to the high incidence of stomach cancer among the Japanese. Yet there is no evi dence that nitrosamines from nitrates and nitrites in the American diet are a threat. For one thing, these sub stances volatilize during cooking, notes Dr. Philippe Shubik, director of the Eppley Institute for Research in Cancer at the University of Nebraska, so exposure to nitrosamine after eating cured meat would be low. More over, nitrites are abundant in saliva. "Every day," notes Dr. Thomas Jukes of the University of California, "we swallow as much nitrite as found in a pound of bacon." Interestingly, vita min C can block formation of nitrosa mines--at least in the test tube. "The same individuals who put themselves at risk by eating bacon every morning," writes Dr. John W. Berg ofthe University of Iowa, "may be protected by preceding the bacon with orange juice." The case against artificial sweeteners is also weak. Some studies made after cyclamates were removed from the mar ket have failed to confirm that cycla mates cause bladder cancer in animals, and the FDA is seriously considering lifting its ban. Although saccharin has been found to cause cancer when im planted directly into the bladder, it is far from clear that it is hazardous if con sumed in the diet. Significantly, diabet ics have been consuming saccharin for years, yet there is no sign that they have a higher than normal cancer risk. Of greater concern is the link between the fatty diet ofaffluent countries and the risk of two of the most prevalent malig nant diseases--cancer of the bowel and breast. Bowel cancer is common in the U.S., butuncommon in Japan, where fish is a staple. However, among Japanese migrating to the U.S. and their children, tlie colon-cancer risk approaches the U.S. level, presumably because of a change in dietary habits. Beef is a likely suspect. The Scots, who consume 20 per cent more beef than their English neigh bors, have one of the world's highest bowel-cancer rates. ^Ilancer of the breast, as well as the prostate, ovary and uterus, is prevalent in most Western countries and may also be related to heavy fat intake. Breast cancer has been finked to overnutrition in women, and fats have been found to promote breast cancer in mice. RSV0024789 Newsweek Drugs: Dangers sometimes outweigh gains MEDICINE Hormones are known to play a part in breast cancer and the current suspicion 2. DRUGS is that fats may overstimulate hormone any epidemiologists are more production or disrupt normal hormone balance. Too much liquor is related to the Mconcerned about the cancer po tential posed by drugs tiian they are about food additives, because drugs development of cancers of the mouth, are taken in relatively large doses. A throat, esophagus, larynx and liver. But certain cancer risk, in some cases, may be the risk is greatest among heavy drinkers outweighed by the seriousness of the who also smoke, giving rise to the belief disorder the drug is designed to beat, so that alcohol is a co-carcinogen, acting in physicians must balance the benefit conjunction with tobacco carcinogens. against the risk. One of the most disturb Among men who drink more than an ing links between a drug and cancer was ounce and a half of liquor a day, the the discovery in 1971 that the daughters mortality from oral cancer is two to six of women who took the synthetic estro times greater than it is for teetotalers, gen diethylstilhestrol (DES) in early depending, in direct proportion, on die pregnancy were susceptible to an often amount they smoke. For heavy drinkers fatal vaginal cancer (box, page 66). and smokers, die risk is up to fifteen DES was given to thousands ofwomen times higher than for those who neither after World War II on die theory that it drink nor smoke. would prevent miscarriage. Much later, Dr. Arthur L. Herbst and his colleagues at Massachusetts General Hospital en countered seven young women with a vaginal adenocarcinoma, a disease that is not only rare, buthad almost neverbefore been found in a woman under the age of 50. Checking the medical histories, the doctors found that all theirpatients'moth ers had used DES in pregnancy. Since that initial report, more than 250 similar cases have been documented. More recently, several studies have suggested that the use of estrogens by middle-aged women to alleviate symp toms of the menopause increases dieir risk of uterine cancer. Researchers at die University of Washington reported tiiat the risk of cancer was nearly five times higher among women who took the hormones than among those who didn't. A major unresolved question is wheth er die birth-control pill--taken by 10 million U.S. women--also poses a cancer risk. In experimental animals, estrogens, which are a constibient of the pills, have r ' CANCER AND THE ENVIRONMENT: TEN TOP SUSPECTS SUBSTANCES ARSENIC ASBESTOS BENZENE BENZIDINE COAL-COMBUSTION PRODUCTS NICKEL COMPOUNDS RADIATION SYNTHETIC ESTROGENS TOBACCO SMOKE | VINYL CHLORIDE WHERE FOUND Mining and smelting industries Brake linings, construction sites, insulations, powerhouses Solvents, oil refineries, insecticides Rubber making, dyestuffs Steel mills, petrochemical industry, asphalt, coal tar Metal industry, alloys Ultraviolet rays from the sun, medical therapy Drugs Cigarettes, pipes, cigars Plastics industry CANCERS THEY MAY CAUSE Skin, lung, liver Lung, pleura, peritoneum Bone marrow Bladder Lung, bladder, scrotum Lung, nasal sinuses Bone marrow, skin, thyroid Vagina, cervix, uterus Lung, bladder, mouth, esophagus, pharynx, larynx Liver, brain y t'pntUi ii t rej et Watch list: In a world full of possible carcinogens, some substances have been identified as particularly dangerous January 26, 1976 RSV0024790 65 rig ^B'Kyv; .* Iv^lJ ' ' W0&', w&&; ?:'ri0>'A m km-- PtHHo* by `left LftU Mrs. Malloy and Marilyn: A drug with a deadly delayed reaction DAUGHTERS OF DES For Grace Malloy, childbearing did had reached her pituitary gland, and not come easily. Although her first Marilyn underwent a grueling six- daughter was bom in 1946 withoutweek regimen of "whole head" radia complications, a subsequent pregnan tion. When all her hair fell out as a re cy ended in miscarriage. When during sult, she still refused to give in to self- r tier next pregnancy she also showed pity and kept up an active social life, signs of miscarrying, her doctor pre wearing a bright scarf over her head. scribed diethylstilbestrol (DES), a ButatnightMrs. Malloy could hearher synthetic estrogen widely used in daughter moaning in pain with the such cases at the time. A second daugh cancer that was continuing its lethal ter, Patti, was delivered in 1951. After spread through her amis, legs, spine yetfanother miscarriage, Mrs. Malloy and brain. Soon she was blind and con became pregnant a fifth time and was fined to a wheelchair. Marilyn died on again given DES. Another daughter, May 26, 1974, two weeks before her Marilyn, was bom in 1956. high-school class's graduation. It was not until Patti and Marilyn Guilt; Today, sitting in her elegant, were 19 and 14 that Grace Malloy read sun-filled La Jolla, Calif., living room, a newspaper report linking DES to a Grace Malloy tells Marilyn's story rare but deadly form ofvaginal cancer with self-control. She does not savor in young women whose mothers had pathos. Nor does she feel any personal taken the hormone during pregnancy. guilt over her daughter's tragic death. Alarmed, Mrs. Malloy asked her doc "I had no way of knowing what those tor if there was anything to this pills would do," she says. "Thousands "scare." "You bet your life there is," of women took them, but we all did it he replied. "You'd better get those in the best of faith, because our doc girls in for an examination right tors prescribed them." away." The result was bad news: Nonetheless, Grace Malloy is not Marilyn had vaginal cancer. without bitterness about what hap Malignancy: In an operation lasting pened to her family--and what still more than twelve hours, Marilyn's may lie ahead. Her older daughter, vagina and nearby lymph glands were Patti, now 25, has been diagnosed as removed; an artificial vagina was con having vaginal adenosis, a lesion that structed using skin grafts from her appears benign but could be the pre legs. The doctors were hopeful that cursor of cancer. In spite of long they had excised the entire malignan standing reservations, Patti recently cy, but a year later they discovered decided to get married, and her doc that the cancer had spread to one lung, tors claim her prospects for a healthy the esophagus and the lining of the future are good. But there is no guar heart. Following another operation, antee; for the time being, Patti can Marilyn recovered sufficiently to re only wait--like thousands of other sume her passion--horseback riding. young women with the same histo A short time later Marilyn's condi ry--and pray that the killer that tion worsened. She lost her appetite, claimed her sister may pass her by. suffered from nausea and severe head --JEAN SELIGMANN with LAWRENCE SHOOK aches. Tests revealed that the cancer n Ua Jolla, Calif. 66 been shown to cause breast cancer. One recent study suggested that the risk of breast cancer was increased for women who took the Pill before having their first child and for those with a history' of benign breast tumors. But at least three other surveys failed to show a connection between oral contraceptives and breast cancer. Drugs used to prevent rejection of organ transplants by suppressing the immune response have also been found to cause cancer. Among more than 6,000 kidney-transplant recipients, the risk of lymphatic cancer was found to be 35 times greater than normal. Of concern to some experts is the fact that one such drug, methotrexate, is being prescribed for the treatment ofsevere psoriasis. 3. RADIATION here is no question that X-rays and Tsimilar forms of radiation can cause leukemia and other forms of cancer ifreceived in high doses. Survivors ofthe Hiroshima and Nagasaki atomic blasts have shown a significantly higher than average incidence ofleukemia, as well as ofcancers ofthe breast, bowel and brain. Recently, it has been found that those treated with radiation in childhood for tonsilitis, enlarged thymus glands and other conditions during the 1940s and 1950s have an increased risk of thyroid cancers. What is not clear, is how much risk there may be from exposure to conventional diagnostic X-rays. According to Lome Houten ofRoswell Park Memorial Institute, Buffalo, N.Y., the amount of radiation from a single abdominal X-ray increases the risk of leukemia. One rad (the standard unit of dosage) of radiation, says Houten, ages the cells it strikes by one year. Thus, a 50year-old man who has received 10 rads has the susceptibility of nonlyniphatic leukemia--a form of the disease that strikes adults---of a 60-year-old. In addi tion, irradiation of men and women dur ing their reproductive years increases the likelihood that their offspring will devel op leukemia. On the basis ofthese obser vations, Houten thinks that no one should undergo routine screening X-rays--in cluding mammography to detect breast cancer--below the age of 50. An excep tion, in his view, would be a woman with a family history ofbreast cancer. But other cancer experts disagree. Dr. Luther Brady of Hahnemann Medical College, for one, disputes Houten's cor relation between diagnostic X-rays and leukemia. "I don't think anybody has confirmed that 1 rad increases the risk of leukemia," he says. E. Cuyler Hammond also disagrees with Houten's feeling about mammography. "The benefit ex ceeds the risk," says Hammond, "if it is a risk at all." Ultraviolet radiation from the sun in creases the risk ofskin cancer. A commit tee of the National Academy of Sciences recently estimated that among white persons living along the 40tli parallel RSV0024791 Newsweek (Philadelphia, for example), 40 per cent cheir work in combination with other of melanomas and 80 per cent of other noxious agents. Mount Sinai Hospital's types of skin cancer could be attributed Irving Selikoff and the ACS's Hammond to ultraviolet rays. Fortunately, most skin found that asbestos workers develop a cancer is slow-growing and has a low higher than normal rate of lung cancer mortality. Melanoma, however, is one of only if they also smoke (although non- the deadliest cancers. Indicative of the smokers among them have high risk of role of sunlight in this tjroe of cancer is colon cancer and an abdominal and chest the fact that the mortality from melanoma tumor called mesothelioma). The inci is 75 per cent higher in the band of states dence of lung cancer among asbestos running from Louisiana to South Caroli workers, in fact, was eight times what it na than in the northern latitudes from was for smokers in other industries and a Washington to Minnesota. startling 92 times the incidence found in nonsmokers. 4. THE WORKPLACE Of considerable concern among the experts is the risk that hazardous sub he list of substances' that threaten stances pose for persons living hear TAmericans in the workplace is long plants or for the families of workers. and growing longer. Chromates, Epidemiologists in South Africa and which are used in paints, pose a hazardEonf gland have found mesothelioma in a lung cancer. Rubber workers have annumber of men and women who had increased risk ofleukemia from exposure never been inside an asbestos plant, to benzene. Lung cancer and lymphoma including a few who had simply lived in have been found to occur at a high rate the households of asbestos workers. In among workers exposed to inorganic the U.S., people living in communities arsenic, which is a basic material in more where there are copper-smelting facili than 40 jobs from tinting windshields to ties have a higher than expected average spraying roses. Like vinyl chloride, arse of lung cancer. Some experts are begin nic has also been linked to liver cancer. ning to uncoverwhat seem to be commu For 80 years, benzidine [used in dye nity-wide effects from vinyl chloride. In making] has been known to cause blad three Ohio towns where vinyl chloride der cancer. It has been withdrawn in was used in industry, researchers have Great Britain, the Soviet Union and found a mysterious number of deaths several other countries, but is still wide from cancers of the central nervous sys ly used in the U.S. tem in the adult population--as well as Many of the occupational carcinogens neural malformations in children. medicine MBWEk ast experts admit that the task of detecting and ultimately controlling all the potential cancercausing threats in the environment is, practically speaking, impossible. But they do insist that if there were legal regulations to screen dangerous chemi cals before they reached the work place--or the home--the risks could be greatly reduced. "Dangerous chemi cals," says Warren Muir of the White House Council on Environmental Qual ity, "can be controlled." . Beyond such enforcement measures, the real task oflowering the incidence of cancers induced by the American life style is essentially up to ordiriaiy citi zens--and here the outlook for construc tive action does not seem so bright. For despite .all the warnings, the majority of Americans continue to indulge them selves in the potentially harmful pleas ures that their opulent society provides, and so far they are apparently content to take the perils along with the pleasures. "Right now we've decided that this is the way we want to live and die," says Dr. David Baltimore, who won a 1975 Nobel Prize for basic cancer research. "And that's the real challenge in American health today." --MATT CLARK with MARIANA GOSNELL and DAN SHAPIRO In NewYork. JAMES BISHOP JR. and EVERT CLARK in Washington and bureau reports WHERE CANCER HITS HARDEST MASS- MORTALITY RATES HIGHER THAN U.S. AVERAGE U.S. AVERAGE LOWER THAN U.S. AVERAGE January 26, 1976 Source; U.S. Department of Health. Education and Welfare Few* *, Frw' 67 RSV0024792