- Email: [email protected]
Diet and cancer: causal relation or just wishful thinking?
162
such medication may give some idea of prognosis while the treatment is continued and whether urgent referral for angiography is needed. When angiography indicates that medical treatment is as justifiable as revascularisation, the result of exercise testing with the patient on medication-a reasonable estimate of the drug’s "cardioprotectiveness" -may influence the choice of management. In the patient with confirmed coronary disease, what is to be made of test results that differ according to whether the patient is on or off treatment? It would be fallacious to label an abnormal test result with the patient off treatment as false positive and misleading to regard a normal result with medication as false negative. Since an exercise-induced drop in ejection fraction or ST-segment depression implies ischaemia, a negative test in a patient on medication indicates that ischaemia is not inducible. What if a test done with a patient on treatment is abnormal? No prospective study with exercise electrocardiography has been done to evaluate this issue. For post-infarction patients taking beta-blockers there is indirect evidence to suggest an adverse outlook if there is at least 2 mm ST depression during exercise electrocardiography. For patients with recent unstable angina (in whom medication withdrawal is unwise) prognosis is worse if the pre-discharge exercise test during drug therapy is positive rather than negative.6 Though the accuracy of the ST-segment/heart rate slope method seems unaffected by beta-blockersthis observation paradoxically limits its usefulness in addressing the effect of medication on the prognostic interpretation of exercise testing. Preliminary radionuclide ventriculographic data show that exercise testing without drug withdrawal may help in the assessment of prognosis in coronary disease.8 In survivors of infarction treated with thrombolysis-a group whose results are often abnormal when exercised without treatment-testing with medication may improve predictive accuracy for recurrent ischaemia.9 In symptom-free patients with residual silent ischaemia during exercise testing after drug withdrawal, suppression of ischaemia by medicaton at repeat testing was associated with improvement in shortterm outcomes These observations support what many clinicians intuitively believe: that an exercise test that is abnormal despite clinically adequate anti-ischaemic medication identifies high-risk patients in whom medical therapy will fail and who will therefore need early revascularisation to improve their prognosis. In retrospect, the prognostic information derived from exercise testing in the randomised studies of surgical versus medical treatment might have been more relevant had testing been done systematically with rather than without medical treatment, since the real issue on trial was early surgery versus continuing with medical treatment, not surgery versus no treatment at all. In conclusion, whether anti-anginal medication should or should not be withdrawn may be influenced by the purpose behind testing. When it is of prime importance to clarify a diagnosis of ischaemic heart disease, we recommend stopping all anti-ischaemic treatment for 3-4 days before testing. When the overriding concern in the patient with a typical history or proven coronary disease is to define the prognosis, we think that testing may give more useful results if done without stopping medication.
2. Gohlke H, Samek L, Betz P, Roskamm H. Exercise testing provides prognostic information in angiographically defined subgroups of patients with coronary artery disease. Circulation 1983; 68: 979-85. 3. Jones RH, McEwan P, Newman GE, et al. Accuracy and diagnosis of coronary artery disease by radionuclide measurement of left ventricular function during rest and exercise. Circulation 1981; 64: 586-601. 4. Ho SWC, McComish MJ, Taylor RR. Effect of beta-adrenergic blockade on the results of exercise testing related to the extent of coronary artery disease. Am J Cardiol 1985; 55: 258-62. 5. Krone RJ, Miller JP, Gillespie JA, Weld FM, and the Multicenter Post-infarction Research Group. Usefulness of low-level exercise testing after acute myocardial infarction in patients taking betablocking agents. Am J Cardiol 1987; 60: 23-27. 6. Wilcox I, Freedman SB, Allman KC, et al. Prognostic significance of a predischarge exercise test in risk stratification after unstable angina pectoris. J Am Coil Cardiol 1991; 18: 677-83. 7. Elamin MS, Boyle R, Kardash MM, et al. Accurate detection of coronary heart disease by new exercise test. Br Heart J 1982; 48: 311-20. 8. Lim R, Dyke L, Dymond DS. Prognostic importance of failure of medical therapy to normalise exercise ejection fraction response in coronary artery disease. J Am Coil Cardiol 1991; 17: 183A. 9. Lim R, Dyke L, Dymond DS. Early prognosis after thrombolysis: value of exercise radionuclide ventriculography performed on anti-ischemic medication. Int J Card Imaging 1991; 7: 125-31. 10. Lim R, Dyke L, Dymond DS. Effect on prognosis of abolition of exercise-induced painless myocardial ischemia by medical therapy. Am J Cardiol 1992; 69: 733-35.
Diet and
causal relation wishful thinking?
cancer:
just
or
The beneficial effects of a prudent diet have been claimed far back as Biblical times (Daniel I, 8-16), but the definition of a healthy diet has varied over generations. In medieval times a lavish intake was favoured, since plump individuals were thought to live longest. At the turn of this century, Rolo Russell began to assert that cancer mortality is highest "in countries that eat more flesh". There was much laboratory activity in the 1940s and 1950sobut in the past three decades the relation between diet and cancer has come under special scrutiny. Existing evidence is based on three sorts of data-indirect relations between the consumption of selected food constituents with cancer incidence and mortality3-’ or time trends in various population groups;8 case control studies;’H1 and laboratory experimentation." The reported correlations are undermined by the fact that human diet does not consist of isolated food components. Furthermore, dietary patterns strongly correlate with social, economic, and political characteristics, all of which could affect cancer risk independently. Therefore, any attempt to isolate one single factor in carcinogenesis may be futile. Long-term prospective studies are not the perfect solution because we cannot determine the time at which
as
carcinogenesis begins. Laboratory experimentations seem much more controllable and more definite, but extrapolation to man is questionable in terms of time, dose, and life patterns. We must also take into consideration
publication bias, whereby "positive" findings are more likely to be printed than "negative". This bias seriously confounds the scientific literature, and cannot be countered by the magic trick of the 1990s-"adjusted for". For example, suppose we interview
REFERENCES 1. Stone
DL, Dymond DS, Elliott AT, Britton KE, Banim SO, Spurrell RAJ. Exercise first pass radionuclide ventriculography in detection of patients with coronary artery disease. Br Heart J 1980; 44: 208-14.
ADDRESS Department of Clinical Epidemiology, Chaim Sheba Medical Center, Tel Hashomer, Israel (Prof B Modan, MD).
163
? women with cervical cancer and 100 controls, and find that the relative risk for once-a-day consumption of strawberry yogurt is 0.25. If no methodological flaws are discovered, the results will be published in a first-league journal, and the yogurt industry will have a ball. Then, let us suppose that 19 other centres have simultaneously conducted studies of the same sort, and all of them find that cervical cancer risk in strawberry yogurt consumers is about the same as in the general population. The authors may have great difficulties in getting the results published: "We do not expect yogurt to protect against cervical cancer, at least not in a sample of one hundred women", they will be told. In other words, good epidemiological data are scarce and mconsistent. There may be one exception-the protection given by high intake of fibre and/or fruits and vegetables against colon cancer.9,13,14 It may operate through modification of carcinogenic metabolites, the composition of intestinal flora, the concentration of biliary end products,15 or transit time (shortening the period of contact between carcinogen and intestinal mucosa).16 Breast cancer may also qualify,11.17 though to a much lower extent: colon and breast cancer are strongly correlated, while cholesterol and bileproducts form building blocks for oestrogen, a known risk factor for breast cancer. Most of these theories are still in the twilight zone, yet
dietary prevention has become a multimillion-dollar industry, with low-fat/low-cholesterol labels on a multitude of commercial products including club soda. Why this exploitation? First, diet seems to be one risk factor amenable to treatment without stopping the wheels of industry. Second, diet is commonly regarded as controllable by almost anybody. Third, most countries do not regulate claims about food, particularly regarding its health effects, with the rigour that they apply to claims about drugs. Finally, food is a universally consumed item that promises a very high
-
investment return. The currently recommended. high-fibre/low-fat/fishbut-no-meat diet may help to prevent various diseases besides cancer. So, one might suppose, no risks are taken. This is not necessarily so. The fish dishes that have been in vogue over the two past decades can be heavily contaminated with residues of common pesticides.18 A survey by the US Consumer Union indicated that 53% of salmon tested, 50% of white fish, and 25% of swordfish contained polychlorinated biphenyls, more popularly known as PCBs. Even though the Environmental Protection Agency banned these potentially carcinogenic pesticides in the 1970s, the residues became widely dispersed because of their slow decomposition. Also, 90% of swordfish and tuna fish were loaded with mercury-another substance that is not supposed to be beneficial to our health. The fate of our vegetables may not be much better .19 We often hear that the best protection against cancer is in our hichen, but can we be sure that these products are uncontaminated by carcinogenic chemicals or by fallout particles. Further, the much-vaunted green leafy vegetables are high in cadmium, an element that strongly competes ’Aith zinc and may constitute a prominent risk factor for prostate cancero (a site that threatens to become the number one in US males). Snll, more studies show a protective effect of fruits and ’;vegetables than not. Is it possible that the detrimental effect ef pesticides and contaminated soil has been completely neutralised by the beneficial effects? Alternatively, the - atency period from exposure to cancer development may be much longer than we have supposed. It seems plausible that,
at least in certain
instances, fruits and vegetables might serve "surrogates" for an unidentified protective factor. To preach an increase in intake of these foods is not necessarily wrong. John Snow21 related the nineteenth century London cholera epidemic to the water supply as
system years before Vibrio cholerae was discovered. Changing the water supply stopped the epidemic. Nevertheless, an exclusive concentration on dietary factors may carry its own risks. The danger is that attention is diverted from issues that are more difficult to handle. Certain risk factors for cancer development are more powerful and more strongly substantiated than dietsmoking, asbestos, radiation, chemical pollutants, to name just a few. Combating these carcinogenic substances is far less simple than advocating change of diet. It would mean either compromising the luxuries of the 21 st century or an uphill battle against industry. In our capitalistic society, the industrial moguls, wrestling for power and money, will join forces with organised labour, fighting for jobs in a worldwide shaky economy. In contrast, adoption of certain dietary measures presents little burden. The data may be marginal but the economic harvest is wild. New products can be developed, such as no-meat hamburgers, sugarless sweeteners, salt-free pretzels and, just around the corner, non-fatty fat that looks like fat, tastes like fat, and will doubtless cost much more than fat. The promotion of these new products not only diverts our attention from certain real causes of cancer, but also stimulates the economy and gives the public a false sense of security. To limit environmental danger, health policy measures should combine the promotion of behavioural changes with enforcement of anti-pollution legislation. Agricultural products must always be protected against biological scavengers, but we shall have to use safer insecticides even if this means lower profits and higher costs; we must draw up a list of preventive priorities in order of importance rather than ease of attainment. Finally, we must not abandon efforts to follow up promising leads concerning diet and cancer by undertaking intervention studies. Such investigations present vast difficulties-since human nature and human appetite are hard to control. Few will deny that there is some connection between diet and cancer, but a sound preventive policy depends on an understanding of the true nature of this relationship. REFERENCES 1. Russell R. Notes on the causation of cancer. London: Longmans, Green, 1916. 2. Tannenbaum A, Silverstone H. Nutrition in relation to cancer. Adv Cancer Res 1953; 1: 451-501. 3. Wynder EL, Fujita Y, Harris RE, Hirayama T, Hiyama T. Comparative epidemiology of cancer between the United States and Japan. A second look. Cancer 1991; 67: 746-63. 4. Philips RL. Role of life-style and dietary habits in risk of cancer among Seventh Day Adventists. Cancer Res 1975; 35: 3513-22. 5. Howell MA. Factor analysis of international cancer mortality data and per capita food consumption. Br J Cancer 1974; 29: 328-36. 6. Kmet J, Mahboubi E. Esophageal cancer in the Caspian Littoral of Iran: initial studies. Science 1972; 175: 846-53. 7. Carrol KK, Gammal EB, Plunkett ER. Dietary fat and mammary cancer. Can Med Assoc J 1968; 98: 590-93. 8. Howson CP, Hiyama T, Wynder EL. The decline in gastric cancer: epidemiology of an unplanned triumph. Epidemiol Rev 1986; 8: 1-27. 9. Modan B, Barell V, Lubin F, Modan M, Greenberg RA, Graham S. Low fiber intake as an etiological factor in cancer of the colon. J Natl Cancer Inst 1975; 55: 15-18. 10. Graham S, Marshall J, Haughey B, et al. Dietary epidemiology of cancer of the colon in Western New York. Am J Epidemiol 1988; 128: 490-503.
164
11. Howe GR, Hirohata T, Hislop TG, et al. Dietary factors and risk of breast cancer: Combined analysis of 12 case-control studies. J Natl Cancer Inst 1990; 82: 561-9. 12. Kritchevsky D. Fat calories and fiber. Prog Clin Biol Res 1986; 222: 495-515. 13. Slattery ML, Sorenson AW, Mahoney AW, French TK, Kritchevsky D, Street JC. Diet and colon cancer: Association of risk by fiber type and food source. J Natl Cancer Inst 1988; 80: 1474-80. 14. Graham S, Mettlin C. Diet and colon cancer. Am J Epidemiol 1979; 109: 1-20. 15. Hill MJ. Bacterias and the etiology of colonic cancer. Cancer 1974; 34: 815-18. 16. Burkitt DP, Walker ARP, Painter NS. Effect of dietary fibre on stools and
Atheroma to Heart Failure: Disease
B OOK S HELF
Z. S. Pawlowski, G. A. Schad, and G. J. Stott. Geneva: World Health Organisation. 1991. Pp 96. Sw Fr 19. ISBN 9241544155.
The two species of hookworm that parasitise man, Ancylostoma duodenale and Necator americanus, are the of
the
soil-transmitted
nematodes
(geohelminths). About one quarter of the world’s population is thought to be infected with hookworms; adult forms live in the upper intestinal tract, attached to the mucosa from which they suck blood. This chronic blood loss makes hookworm infection a disease of substantial public health importance in many areas of the developing world. Hookworm infection only becomes hookworm disease in a fraction of infected individuals and the factors responsible for this switch include worm load, species, and pre-existing iron balance. It is not surprising that it is the women and children of the poorer, rural communities in the tropics who bear the brunt of the disease worldwide. While large-scale attempts to control hookworm infection have generally been unsuccessful, reduction of severe hookworm anaemia can be achieved through well-managed intervention programmes that focus on improved sanitation, mass chemotherapy with anthelmintics and iron, and health education among the community. Broad-spectrum anthelmintics, such as albendazole and mebendazole, can be given as a single-dose once or twice a year, in mass chemotherapy campaigns aimed at whole populations. This strategy was recommended at a recent conference on the health of school-age children held in Bellagio (Lancet 1991; 338: 686-87). Hookworm Infection and Anaemia is intended as a practical management guide, and is aimed mainly at community health workers. It is a high-quality work, remarkably well produced and edited, and has no important factual errors. It is perhaps characteristic of the World Health Organisation (WHO) to publish a book that exclusively concentrates on a single disease intervention, when the accepted wisdom in the field, and WHO’s own stated policy, is that only an integrated approach to the simultaneous control of all major geohelminths (including
hookworm, ascaris, strongyloides, and trichuris) is likely to prove practicable. Despite this caveat, I am sure that health professionals world wide will find this booklet both appealing and helpful. Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK
a
Continuum of
Edited by R. H. Anderson, P. A. Poole-Wilson, and M. H. Yacoub. Oxford: Butterworth Heinemann. 1991. Pp 193. /;45. ISBN 0-750613351.
Hookworm Infection and Anaemia
commonest
role in the causation of disease. Lancet 1972; ii 1408-11. 17. Lubin F, Wax Y, Modan B. Role of fat, animal protein and dietary fiber in breast cancer etiology. A case control study. J Natl Cancer Inst 1986; 77: 605-12. 18. Regulating pesticides in food. The Delaney paradox. Washington, DC National Academic Press, 1987. 19. Baker SB, Wilkinson CF, eds. The effects of pesticides on human health. Adv Modern Envir Toxicol 1990; 18: 1-438. 20. Eighany NA, Schumacher MC, Slattery ML, West DW, Lee JS. Occupation, cadmium exposure, and prostate cancer. Epidemology 1990; 1: 107-15. 21. Snow J. Snow on cholera. New York: Hafner, 1945.
transit-times, and its
MARCEL HOMMEL
During the past decade, the Brompton and National Hospitals have metamorphosed into the Royal Brompton & National Heart and Lung Hospital and the National Heart & Lung Institute. Major US institutes are known for their regular publications that act not only as educational material but also as a shop window for their many and varied talents. This volume is a production along similar lines and represents the first of a series of "Royal Brompton reviews" that are planned to encompass several cardiac and pulmonary topics. Its success is assured by generous support from the pharmaceutical industry who have so far provided me with two unsolicited copies to add to Heart
the review copy. This first volume covers various aspects of ischaemic heart disease, which are presented as a continuum-
predisposing factors, imaging, pathophysiology, ischaemia, infarction and its
acute
management, risk stratification
postinfarction, hypertrophy, failure, transplantation, and sudden death. The book has its roots in a symposium, but the editors have worked hard to iron out differences in style. Twelve of the twenty-four authors are connected with the National Heart & Lung Institute. Contributions have been scrutinised by a distinguished international editorial board to counter any criticism that this might be a rather cosy production. Most chapters take the form of review articles, the highlight being a splendid and prophetic account of the relevance of magnetic resonance to the management and early diagnosis of coronary vascular disease. All authors do themselves justice but I would pick out the chapters on stratification of risk after myocardial infarction and the management of the cardiac transplant patient as being especially helpful and interesting. Few original data are presented, with the chapter on molecular and cellular changes in ventricular hypertrophy and failure being an exception. All the chapters are well referenced. This book has limitations inherent in its design and background, yet a glance at the contents page reveals most of the buzz words in contemporary cardiology. It gives ani intriguing picture of current thought in ischaemic heart disease and looks to future developments, so leaving the reader well informed on many issues. The doctor fortunate enough to receive a free copy from his local pharmaceutical I i representative would be strongly advised to read it. Department of Cardiology, Northern General Hospital, Sheffield S5 7AU, UK
G. D. G. OAKLEY
such medication may give some idea of prognosis while the treatment is continued and whether urgent referral for angiography is needed. When angiography indicates that medical treatment is as justifiable as revascularisation, the result of exercise testing with the patient on medication-a reasonable estimate of the drug’s "cardioprotectiveness" -may influence the choice of management. In the patient with confirmed coronary disease, what is to be made of test results that differ according to whether the patient is on or off treatment? It would be fallacious to label an abnormal test result with the patient off treatment as false positive and misleading to regard a normal result with medication as false negative. Since an exercise-induced drop in ejection fraction or ST-segment depression implies ischaemia, a negative test in a patient on medication indicates that ischaemia is not inducible. What if a test done with a patient on treatment is abnormal? No prospective study with exercise electrocardiography has been done to evaluate this issue. For post-infarction patients taking beta-blockers there is indirect evidence to suggest an adverse outlook if there is at least 2 mm ST depression during exercise electrocardiography. For patients with recent unstable angina (in whom medication withdrawal is unwise) prognosis is worse if the pre-discharge exercise test during drug therapy is positive rather than negative.6 Though the accuracy of the ST-segment/heart rate slope method seems unaffected by beta-blockersthis observation paradoxically limits its usefulness in addressing the effect of medication on the prognostic interpretation of exercise testing. Preliminary radionuclide ventriculographic data show that exercise testing without drug withdrawal may help in the assessment of prognosis in coronary disease.8 In survivors of infarction treated with thrombolysis-a group whose results are often abnormal when exercised without treatment-testing with medication may improve predictive accuracy for recurrent ischaemia.9 In symptom-free patients with residual silent ischaemia during exercise testing after drug withdrawal, suppression of ischaemia by medicaton at repeat testing was associated with improvement in shortterm outcomes These observations support what many clinicians intuitively believe: that an exercise test that is abnormal despite clinically adequate anti-ischaemic medication identifies high-risk patients in whom medical therapy will fail and who will therefore need early revascularisation to improve their prognosis. In retrospect, the prognostic information derived from exercise testing in the randomised studies of surgical versus medical treatment might have been more relevant had testing been done systematically with rather than without medical treatment, since the real issue on trial was early surgery versus continuing with medical treatment, not surgery versus no treatment at all. In conclusion, whether anti-anginal medication should or should not be withdrawn may be influenced by the purpose behind testing. When it is of prime importance to clarify a diagnosis of ischaemic heart disease, we recommend stopping all anti-ischaemic treatment for 3-4 days before testing. When the overriding concern in the patient with a typical history or proven coronary disease is to define the prognosis, we think that testing may give more useful results if done without stopping medication.
2. Gohlke H, Samek L, Betz P, Roskamm H. Exercise testing provides prognostic information in angiographically defined subgroups of patients with coronary artery disease. Circulation 1983; 68: 979-85. 3. Jones RH, McEwan P, Newman GE, et al. Accuracy and diagnosis of coronary artery disease by radionuclide measurement of left ventricular function during rest and exercise. Circulation 1981; 64: 586-601. 4. Ho SWC, McComish MJ, Taylor RR. Effect of beta-adrenergic blockade on the results of exercise testing related to the extent of coronary artery disease. Am J Cardiol 1985; 55: 258-62. 5. Krone RJ, Miller JP, Gillespie JA, Weld FM, and the Multicenter Post-infarction Research Group. Usefulness of low-level exercise testing after acute myocardial infarction in patients taking betablocking agents. Am J Cardiol 1987; 60: 23-27. 6. Wilcox I, Freedman SB, Allman KC, et al. Prognostic significance of a predischarge exercise test in risk stratification after unstable angina pectoris. J Am Coil Cardiol 1991; 18: 677-83. 7. Elamin MS, Boyle R, Kardash MM, et al. Accurate detection of coronary heart disease by new exercise test. Br Heart J 1982; 48: 311-20. 8. Lim R, Dyke L, Dymond DS. Prognostic importance of failure of medical therapy to normalise exercise ejection fraction response in coronary artery disease. J Am Coil Cardiol 1991; 17: 183A. 9. Lim R, Dyke L, Dymond DS. Early prognosis after thrombolysis: value of exercise radionuclide ventriculography performed on anti-ischemic medication. Int J Card Imaging 1991; 7: 125-31. 10. Lim R, Dyke L, Dymond DS. Effect on prognosis of abolition of exercise-induced painless myocardial ischemia by medical therapy. Am J Cardiol 1992; 69: 733-35.
Diet and
causal relation wishful thinking?
cancer:
just
or
The beneficial effects of a prudent diet have been claimed far back as Biblical times (Daniel I, 8-16), but the definition of a healthy diet has varied over generations. In medieval times a lavish intake was favoured, since plump individuals were thought to live longest. At the turn of this century, Rolo Russell began to assert that cancer mortality is highest "in countries that eat more flesh". There was much laboratory activity in the 1940s and 1950sobut in the past three decades the relation between diet and cancer has come under special scrutiny. Existing evidence is based on three sorts of data-indirect relations between the consumption of selected food constituents with cancer incidence and mortality3-’ or time trends in various population groups;8 case control studies;’H1 and laboratory experimentation." The reported correlations are undermined by the fact that human diet does not consist of isolated food components. Furthermore, dietary patterns strongly correlate with social, economic, and political characteristics, all of which could affect cancer risk independently. Therefore, any attempt to isolate one single factor in carcinogenesis may be futile. Long-term prospective studies are not the perfect solution because we cannot determine the time at which
as
carcinogenesis begins. Laboratory experimentations seem much more controllable and more definite, but extrapolation to man is questionable in terms of time, dose, and life patterns. We must also take into consideration
publication bias, whereby "positive" findings are more likely to be printed than "negative". This bias seriously confounds the scientific literature, and cannot be countered by the magic trick of the 1990s-"adjusted for". For example, suppose we interview
REFERENCES 1. Stone
DL, Dymond DS, Elliott AT, Britton KE, Banim SO, Spurrell RAJ. Exercise first pass radionuclide ventriculography in detection of patients with coronary artery disease. Br Heart J 1980; 44: 208-14.
ADDRESS Department of Clinical Epidemiology, Chaim Sheba Medical Center, Tel Hashomer, Israel (Prof B Modan, MD).
163
? women with cervical cancer and 100 controls, and find that the relative risk for once-a-day consumption of strawberry yogurt is 0.25. If no methodological flaws are discovered, the results will be published in a first-league journal, and the yogurt industry will have a ball. Then, let us suppose that 19 other centres have simultaneously conducted studies of the same sort, and all of them find that cervical cancer risk in strawberry yogurt consumers is about the same as in the general population. The authors may have great difficulties in getting the results published: "We do not expect yogurt to protect against cervical cancer, at least not in a sample of one hundred women", they will be told. In other words, good epidemiological data are scarce and mconsistent. There may be one exception-the protection given by high intake of fibre and/or fruits and vegetables against colon cancer.9,13,14 It may operate through modification of carcinogenic metabolites, the composition of intestinal flora, the concentration of biliary end products,15 or transit time (shortening the period of contact between carcinogen and intestinal mucosa).16 Breast cancer may also qualify,11.17 though to a much lower extent: colon and breast cancer are strongly correlated, while cholesterol and bileproducts form building blocks for oestrogen, a known risk factor for breast cancer. Most of these theories are still in the twilight zone, yet
dietary prevention has become a multimillion-dollar industry, with low-fat/low-cholesterol labels on a multitude of commercial products including club soda. Why this exploitation? First, diet seems to be one risk factor amenable to treatment without stopping the wheels of industry. Second, diet is commonly regarded as controllable by almost anybody. Third, most countries do not regulate claims about food, particularly regarding its health effects, with the rigour that they apply to claims about drugs. Finally, food is a universally consumed item that promises a very high
-
investment return. The currently recommended. high-fibre/low-fat/fishbut-no-meat diet may help to prevent various diseases besides cancer. So, one might suppose, no risks are taken. This is not necessarily so. The fish dishes that have been in vogue over the two past decades can be heavily contaminated with residues of common pesticides.18 A survey by the US Consumer Union indicated that 53% of salmon tested, 50% of white fish, and 25% of swordfish contained polychlorinated biphenyls, more popularly known as PCBs. Even though the Environmental Protection Agency banned these potentially carcinogenic pesticides in the 1970s, the residues became widely dispersed because of their slow decomposition. Also, 90% of swordfish and tuna fish were loaded with mercury-another substance that is not supposed to be beneficial to our health. The fate of our vegetables may not be much better .19 We often hear that the best protection against cancer is in our hichen, but can we be sure that these products are uncontaminated by carcinogenic chemicals or by fallout particles. Further, the much-vaunted green leafy vegetables are high in cadmium, an element that strongly competes ’Aith zinc and may constitute a prominent risk factor for prostate cancero (a site that threatens to become the number one in US males). Snll, more studies show a protective effect of fruits and ’;vegetables than not. Is it possible that the detrimental effect ef pesticides and contaminated soil has been completely neutralised by the beneficial effects? Alternatively, the - atency period from exposure to cancer development may be much longer than we have supposed. It seems plausible that,
at least in certain
instances, fruits and vegetables might serve "surrogates" for an unidentified protective factor. To preach an increase in intake of these foods is not necessarily wrong. John Snow21 related the nineteenth century London cholera epidemic to the water supply as
system years before Vibrio cholerae was discovered. Changing the water supply stopped the epidemic. Nevertheless, an exclusive concentration on dietary factors may carry its own risks. The danger is that attention is diverted from issues that are more difficult to handle. Certain risk factors for cancer development are more powerful and more strongly substantiated than dietsmoking, asbestos, radiation, chemical pollutants, to name just a few. Combating these carcinogenic substances is far less simple than advocating change of diet. It would mean either compromising the luxuries of the 21 st century or an uphill battle against industry. In our capitalistic society, the industrial moguls, wrestling for power and money, will join forces with organised labour, fighting for jobs in a worldwide shaky economy. In contrast, adoption of certain dietary measures presents little burden. The data may be marginal but the economic harvest is wild. New products can be developed, such as no-meat hamburgers, sugarless sweeteners, salt-free pretzels and, just around the corner, non-fatty fat that looks like fat, tastes like fat, and will doubtless cost much more than fat. The promotion of these new products not only diverts our attention from certain real causes of cancer, but also stimulates the economy and gives the public a false sense of security. To limit environmental danger, health policy measures should combine the promotion of behavioural changes with enforcement of anti-pollution legislation. Agricultural products must always be protected against biological scavengers, but we shall have to use safer insecticides even if this means lower profits and higher costs; we must draw up a list of preventive priorities in order of importance rather than ease of attainment. Finally, we must not abandon efforts to follow up promising leads concerning diet and cancer by undertaking intervention studies. Such investigations present vast difficulties-since human nature and human appetite are hard to control. Few will deny that there is some connection between diet and cancer, but a sound preventive policy depends on an understanding of the true nature of this relationship. REFERENCES 1. Russell R. Notes on the causation of cancer. London: Longmans, Green, 1916. 2. Tannenbaum A, Silverstone H. Nutrition in relation to cancer. Adv Cancer Res 1953; 1: 451-501. 3. Wynder EL, Fujita Y, Harris RE, Hirayama T, Hiyama T. Comparative epidemiology of cancer between the United States and Japan. A second look. Cancer 1991; 67: 746-63. 4. Philips RL. Role of life-style and dietary habits in risk of cancer among Seventh Day Adventists. Cancer Res 1975; 35: 3513-22. 5. Howell MA. Factor analysis of international cancer mortality data and per capita food consumption. Br J Cancer 1974; 29: 328-36. 6. Kmet J, Mahboubi E. Esophageal cancer in the Caspian Littoral of Iran: initial studies. Science 1972; 175: 846-53. 7. Carrol KK, Gammal EB, Plunkett ER. Dietary fat and mammary cancer. Can Med Assoc J 1968; 98: 590-93. 8. Howson CP, Hiyama T, Wynder EL. The decline in gastric cancer: epidemiology of an unplanned triumph. Epidemiol Rev 1986; 8: 1-27. 9. Modan B, Barell V, Lubin F, Modan M, Greenberg RA, Graham S. Low fiber intake as an etiological factor in cancer of the colon. J Natl Cancer Inst 1975; 55: 15-18. 10. Graham S, Marshall J, Haughey B, et al. Dietary epidemiology of cancer of the colon in Western New York. Am J Epidemiol 1988; 128: 490-503.
164
11. Howe GR, Hirohata T, Hislop TG, et al. Dietary factors and risk of breast cancer: Combined analysis of 12 case-control studies. J Natl Cancer Inst 1990; 82: 561-9. 12. Kritchevsky D. Fat calories and fiber. Prog Clin Biol Res 1986; 222: 495-515. 13. Slattery ML, Sorenson AW, Mahoney AW, French TK, Kritchevsky D, Street JC. Diet and colon cancer: Association of risk by fiber type and food source. J Natl Cancer Inst 1988; 80: 1474-80. 14. Graham S, Mettlin C. Diet and colon cancer. Am J Epidemiol 1979; 109: 1-20. 15. Hill MJ. Bacterias and the etiology of colonic cancer. Cancer 1974; 34: 815-18. 16. Burkitt DP, Walker ARP, Painter NS. Effect of dietary fibre on stools and
Atheroma to Heart Failure: Disease
B OOK S HELF
Z. S. Pawlowski, G. A. Schad, and G. J. Stott. Geneva: World Health Organisation. 1991. Pp 96. Sw Fr 19. ISBN 9241544155.
The two species of hookworm that parasitise man, Ancylostoma duodenale and Necator americanus, are the of
the
soil-transmitted
nematodes
(geohelminths). About one quarter of the world’s population is thought to be infected with hookworms; adult forms live in the upper intestinal tract, attached to the mucosa from which they suck blood. This chronic blood loss makes hookworm infection a disease of substantial public health importance in many areas of the developing world. Hookworm infection only becomes hookworm disease in a fraction of infected individuals and the factors responsible for this switch include worm load, species, and pre-existing iron balance. It is not surprising that it is the women and children of the poorer, rural communities in the tropics who bear the brunt of the disease worldwide. While large-scale attempts to control hookworm infection have generally been unsuccessful, reduction of severe hookworm anaemia can be achieved through well-managed intervention programmes that focus on improved sanitation, mass chemotherapy with anthelmintics and iron, and health education among the community. Broad-spectrum anthelmintics, such as albendazole and mebendazole, can be given as a single-dose once or twice a year, in mass chemotherapy campaigns aimed at whole populations. This strategy was recommended at a recent conference on the health of school-age children held in Bellagio (Lancet 1991; 338: 686-87). Hookworm Infection and Anaemia is intended as a practical management guide, and is aimed mainly at community health workers. It is a high-quality work, remarkably well produced and edited, and has no important factual errors. It is perhaps characteristic of the World Health Organisation (WHO) to publish a book that exclusively concentrates on a single disease intervention, when the accepted wisdom in the field, and WHO’s own stated policy, is that only an integrated approach to the simultaneous control of all major geohelminths (including
hookworm, ascaris, strongyloides, and trichuris) is likely to prove practicable. Despite this caveat, I am sure that health professionals world wide will find this booklet both appealing and helpful. Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK
a
Continuum of
Edited by R. H. Anderson, P. A. Poole-Wilson, and M. H. Yacoub. Oxford: Butterworth Heinemann. 1991. Pp 193. /;45. ISBN 0-750613351.
Hookworm Infection and Anaemia
commonest
role in the causation of disease. Lancet 1972; ii 1408-11. 17. Lubin F, Wax Y, Modan B. Role of fat, animal protein and dietary fiber in breast cancer etiology. A case control study. J Natl Cancer Inst 1986; 77: 605-12. 18. Regulating pesticides in food. The Delaney paradox. Washington, DC National Academic Press, 1987. 19. Baker SB, Wilkinson CF, eds. The effects of pesticides on human health. Adv Modern Envir Toxicol 1990; 18: 1-438. 20. Eighany NA, Schumacher MC, Slattery ML, West DW, Lee JS. Occupation, cadmium exposure, and prostate cancer. Epidemology 1990; 1: 107-15. 21. Snow J. Snow on cholera. New York: Hafner, 1945.
transit-times, and its
MARCEL HOMMEL
During the past decade, the Brompton and National Hospitals have metamorphosed into the Royal Brompton & National Heart and Lung Hospital and the National Heart & Lung Institute. Major US institutes are known for their regular publications that act not only as educational material but also as a shop window for their many and varied talents. This volume is a production along similar lines and represents the first of a series of "Royal Brompton reviews" that are planned to encompass several cardiac and pulmonary topics. Its success is assured by generous support from the pharmaceutical industry who have so far provided me with two unsolicited copies to add to Heart
the review copy. This first volume covers various aspects of ischaemic heart disease, which are presented as a continuum-
predisposing factors, imaging, pathophysiology, ischaemia, infarction and its
acute
management, risk stratification
postinfarction, hypertrophy, failure, transplantation, and sudden death. The book has its roots in a symposium, but the editors have worked hard to iron out differences in style. Twelve of the twenty-four authors are connected with the National Heart & Lung Institute. Contributions have been scrutinised by a distinguished international editorial board to counter any criticism that this might be a rather cosy production. Most chapters take the form of review articles, the highlight being a splendid and prophetic account of the relevance of magnetic resonance to the management and early diagnosis of coronary vascular disease. All authors do themselves justice but I would pick out the chapters on stratification of risk after myocardial infarction and the management of the cardiac transplant patient as being especially helpful and interesting. Few original data are presented, with the chapter on molecular and cellular changes in ventricular hypertrophy and failure being an exception. All the chapters are well referenced. This book has limitations inherent in its design and background, yet a glance at the contents page reveals most of the buzz words in contemporary cardiology. It gives ani intriguing picture of current thought in ischaemic heart disease and looks to future developments, so leaving the reader well informed on many issues. The doctor fortunate enough to receive a free copy from his local pharmaceutical I i representative would be strongly advised to read it. Department of Cardiology, Northern General Hospital, Sheffield S5 7AU, UK
G. D. G. OAKLEY