Prospects for cancer control in the 1990s.

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1990. 11:143-63

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PROSPECTS FOR CANCER CONTROL IN THE 1990s C. S. Muir and A. J. Sasco International Agency for Research on Cancer, 150, Cours Albert-Thomas, 69372 Lyon, Cedex 08, France

INTRODUCTION Around

1618 Thomas Adams wrote "He is a better physician that keepes

diseases off us, than he that cures them being on us; prevention is so much better than healing because it saves the labour of being sick" stand some

(1). Where do we

370 years later?

This review examines the current and possible future world cancer burden, identifies the sites of cancer for which a better understanding of etiology is urgently needed (for without knowledge of cause, rational prevention is difficult), and sets these topics in the context of cancer prevention today and tomorrow.

The World Cancer Burden: Today and Tomorrow Before addressing the control of cancer, knowledge of the present cancer burden and its possible evolution in the coming ten years is essential. Although national figures for cancer mortality have been available for

for incidence for a 1950 (Figure I), not until recently was any attempt made to assess the world cancer burden (37). This estimate was -recently updated (38) for 1980, when it was determined that around 6.5 many countries since the tum of the century, and figures smaller number of populations since

million new cases o f cancer could b e expected, almost equally divided between the developed and developing world (where, however, two thirds of the world's population lives). Wide differences are found in the pattern of cancer sites in the 24 demographic regions recognized by the United Nations 143

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MUIR & SASCO

144

AREA

POPULATION. MILLIONS

4453� ____ �"�� '� ' �====Jf-----r----�----�

WORLD DEVELOPED COUNTRIES

1134

DEVELOPING COUNTRIES

3317

E

LA TIN AMERICA

476 � 362 r-

NORTH AMERICA

252

AFRICA


��-riliii-ii -r-IiiIi�iiI ===rl!llimlIi< i

2591 48 4 23 265

ASIA EUROPE OCEANIA USSR

Percentage coverage

.,.

�� P '

0%

20%

Figure 1 area.

80 %

60 %

40 %

o M ORTALITY

100%

II INCIDENCE

Availability around 1980 of cancer mortality and incidence data by United Nations

for which Parkin et al (38) present data. The six most common sites, globally speaking, which account for nearly 60% of the world cancer burden, are given in Table 1. A DEMOGRAPHIC NIGHTMARE

In many parts of the world, the average age

of the population is rising. As cancer is more common in older persons, the total number of persons with cancer will increase on demographic grounds alone. Nevertheless, substantial demography-linked increases in the

cancer

burden in developing countries will be delayed for some time, as young persons will predominate in population pyramid for the next

30 years or so.

The situation may be quite different in Europe (47). Table 1

The most frequent cancers world-wide. 1980 Number"

%

2. Stomach

513. 6 408. 8

(15.8) (12.6)

Males

I. Lung

Females

Number"

1. Breast 2. Cervix

57 2. 1 465.6

% (18.4) (15.0) (9.2)

3. Colon/rectum

286. 2

4. Mouth/pharynx

257.3

( 8.8 ) (7.9)

3. Colon/rectum 4. Stomach

285. 9 260.6

5. Prostate

235.8

(7.3)

5. Corpus uteri

148.8

(4.8)

202. 1 3246.6

(6.2)

6. Lung

146.9 3103. 1

(4.7)

6. Esophagus

All sites •

Numbers are in thousands.

All sites

(8.4)


CANCER CONTROL IN THE 1990s

145

Given current demographic trends and likely future trends in risk, eastern and southern Europe will have to provide the facilities and manpower for the diagnosis and treatment of about 60% more cancer patients in 2000 than in 1975 (33). In the north and west of Europe, the increase will probably be around 15% as the major demographic changes have already taken place. No country, however prosperous, can face the costs involved in the increasingly complex diagnosis and treatment of ever-mounting numbers of cancer patients, and the need for a reduction in their number is axiomatic. Ten million new cancer cases a year by 2020 would represent a 1.4% average annual increase since 1980--an all too plausible rise in the global cancer burden. Having adduced figures for the current and the short-term future cancer burden, any consideration of control must also address the issue of etiological exposures to assess whether any changes in the prevalence of risk factors is foreseeable. As seen from Table 1, the major cause of the most frequent cancer in males, tobacco smoking, has been known since at least 1940, and was suspected by clinicians long before then. In the 1950s, the first sound epidemiological studies on this topic were published, followed by hundreds of other studies confirming the causal role of smoking in lung cancer. Tobacco, whether smoked or chewed, by itself and even more so in association with alcohol, plays a major role in the occurrence of cancer of the mouth/pharynx and also contributes to cancer of the esophagus (24, 25). The causes of the other leading cancers are less clear but it is generally recognized that in some ways diet is implicated in cancers of the digestive tract as well as in hormone dependent cancers, such as prostate. For females the leading site is breast cancer: Precise etiology remains elusive. Reproductive and contraceptive experience, diet, alcohol use, and radiation exposure have, among others, been implicated as risk factors. A hormonal etiology, probably diet-influenced, is likely but the precise phys iopathological pathway is still not understood. Hormones are also important for cancer of the corpus uteri, whereas cervix cancer behaves differently and has probably an infectious origin. Lung cancer and digestive tract cancers have the same causes as in males. In the coming ten years, changes are likely to continue to occur in the incidence of cancer at leading sites because of modifications in (a) the size and age-structure of populations at risk, as discussed above, and (b) the prevalence of risk factors.

POSSIBLE CHANGE IN RISK

Overall figures for tobacco smoking may be somewhat mislead ing. In most, but not all, western countries, the smoking prevalence rates are

TOBACCO


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generally declining in males but increasing in females. Even more perturbing is the high prevalence of tobacco use among adolescents and the advent of so-called smokeless tobacco. In Europe, teenagers start smoking at a young age-around 13 years old-and a substantial proportion are smokers by their late teens. Equally worrisome is the current trend of a regular increase in tobacco consumption in developing countries. Although the rise is but 1 to 2% per year, the number of persons involved is very large. This will inevitably add lung cancer to the present burden of oropharyngeal cancer from the use of smokeless tobacco in some of these countries, e.g. the Indian subcontinent. Efforts to combat smoking are increasing in some parts of the world. In the US, in particular, extensive smoking control programs have been established. Through multimedia, multitarget intensive intervention, the aim of reducing the smoking rate to about 15% by the year 2000 may be achieved. Not all countries have similar targets or means, however. Some decrease in smoking rates will probably be seen in many western countries but, as noted above, this decrease will be more than counter-balanced globally by the increase in consumption in most developing countries. A note of hope comes from some Asian countries, which, with the help of American Public Health Authorities, are trying to close their markets to imported foreign cigarettes, which are often high in both nicotine and tar. The consequences of these changes in tobacco consumption will continue to be seen well into the next century. In the next ten years, lung cancer incidence rates for males will continue to decline in countries where smoking rates have already been diminishing during the last 15 years, such as Finland, the US, and UK, but rates for females will continue to rise. In other regions, such as southern Europe and the developing world, rates will increase in both sexes. Given that the products sold in the developing world have a tar content much higher than those sold elsewhere, the year 2020 should see an explosion in lung cancer incidence. (Unlike possible dietary interventions discussed below, it has been proved that smoking cessation reduces risk-a fact that should be given more emphasis.) DIET In contrast to possible changes in smoking behavior, which can be estimated, although not precisely, modifications in diet are slower to occur and may be less easy to predict. There can be little doubt that the decrease over the past 20 years in coronary heart disease mortality in the United States and Australia is due to dietary changes. Changes in cancer incidence have already taken place. For example, the almost universal decline in gastric cancer has been tentatively linked to modification in food preparation and preservation (smoking, salting, and pickling). (It seems scarcely credible that the mortality from gastric cancer in the US at the tum of the century was probably about the current Japanese level. ) Nevertheless, this relationship has



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never been convincingly demonstrated. Most of the weight of the evidence for a dietary role in the decrease in gastric cancer incidence rests on correlation studies, with added support from several case-control studies that have repeat edly shown in several countries a protective effect for fresh fruit and veget ables. Although it decreased in incidence, if figures for both sexes are combined, stomach cancer was still in first rank around 1980, being marginal ly more frequent than lung cancer. By the year 2000, given the virtually universal fall in the incidence of gastric cancer, even in countries such as Japan which have hitherto had very high rates, it is likely that lung cancer will be ranked as the most frequent cancer. Other common cancers such as colon/rectum, breast, and prostate have also been linked to diet. Increases are ascribed to a "western-type" diet. Some of these cancers could thus be considered to be a result of relative "affluence." The incidence of female breast cancer, which seems to have stabilized in several western populations, is increasing rapidly in populations hitherto at low risk. It is now the most common cancer in women. Age-standardized incidence rates in North America and parts of Western Europe are approx imately in the 55-75/100,000 per annum range. These rates are much lower in parts of Eastern Europe where sizeable urban/rural differentials exist. Thus the incidence in Cracow City was 39.6 in 1978-1982, and 18.4 in rural Novy Sacz not too far away. Incidence rates in Shanghai and Tianjin, China, are just under 20. Among Singapore Chinese rates are 27.1; in Hawaiian Chinese, 57.5 (34). Comparable differentials exist for Japanese women in Japan and those residing in Hawaii. If, as seems likely, breast cancer risk is influenced by diet, then as material prosperity increases and dietary items that contain saturated fat, such as beef, are consumed in increasing quantities, it seems inevitable that the breast cancer burden will also rise. A rise from the current estimated crude rate of 6. 4 per 100,000 for China (38) to that of 20 per 100,000 for urban China (Shanghai), would imply an increase of 65,000 new cases a year across the country: A rise to the incidence level of Hawaiian Chinese would result in 300,000 new cases annually. This is more than a hypothetical possibility. The restrictions placed on family size and the encouragement to have children at a later age are likely to increase the risk. The sheer current and possible future burden of breast cancer makes discovering more about the causes of this disease imperative. Some of these considerations also apply to cancers of the large bowel and prostate, which have been linked to diet. Although the evidence from studies of migrant workers, geographical differences, groups like the Seventh Day Adventists, etc suggests a major role for diet in both increasing and diminish ing risk, the results of case-control studies are frequently contradictory for fat and, to a lesser extent, fiber (42). The incertitude is further compounded by the difficulty of studying with retrospective epidemiological methods the

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relevant period for the etiology of disease. The evidence from studies of Japanese migrants to the US (16) for large bowel cancer could be interpreted as representing exposure in the host country to promoting agents or to potent initiators absent in Japan. Studies in Denmark and Sweden of the colon cancer risk of the spouses of colon cancer patients, however, showed that the mortality in spouses was that of the general population, a finding that could be interpreted as indicating that risk was set before the period of a shared dietary environment began (26, 3 1). The same remark applies to breast cancer, for


which it is possible that the most important events may occur around the time of puberty. More and more knowledge is accumulating on perinatal and multigeneration carcinogenesis. Could risk be influenced in utero or indeed before conception (36)? Even though knowledge of the etiology of colon cancer is still far from perfect, it can nevertheless be predicted that if dietary factors linked to a "western" life-style do operate for large bowel and prostate (and they seem to do so), the global burden of these sites too will rise. OCCUPATIONAL EXPOSURES

In contrast to diet and to a lesser degree

smoking, which affect the general population, certain exposures only occur in

the occupational setting. Their impact is usually low in terms of overall public health, because even if the risks are large, they are confined to small pop ulations. It seems none the less remarkable that some sectors of industry still try to deny the existence of risk for their workforce. The enormous sums to be paid in compensation to asbestos-exposed workers, sums that would have been much better invested in eliminating the risk, are partly due to a willful ostrich policy. A safe product from a safe workplace is not an unreasonable target for the year 2000. The impact of changing occupational exposures on overall mortality or cancer incidence, however, probably will be too small to be monitored through national statistics, and industry-specific surveillance will be needed. In developing countries, an additional problem will be the absence of reliable baseline data to monitor possible future trends. Remarkably little is known about the carcinogenic exposures associated with artisanal or cottage industry in developing countries-Dther than, for example, benzene-associated leukemia in the shoe industry in Turkey. The export of hazards in the form of obsolete plants and manufacture of known toxic chemicals from developed to developing countries could lead to future increases in occupational cancers in parts of the world not yet affected. Dumping, illegal and otherwise, of chemical and other wastes in some poor countries may affect the general population living nearby, although such effects have not been convincingly shown elsewhere. The emergence of biochemical tests-for example, the ability to hydroxyl ate debrisoquine, which may be linked to lung cancer susceptibility (7), and


149


the demonstration that slow acetylators are at risk for bladder cancer induced by aromatic amines not only from industrial sources but also from tobacclr opens the possibility of developing a risk profile for individuals. Although such an approach would be welcome-mass screening at birth might be feasible-some susceptibilities would preclude employment in certain in dustries and would give rise to an ethical dilemma: work but with a risk of cancer, or no work and a lesser risk of cancer (see also section on developing countries). Ideally, it is the working conditions that should be corrected.

Epidemiology: The Critical but Neglected Science The analytical epidemiologist, believing that rational prevention demands a knowledge of cause, would hence wish to concentrate efforts on the common cancers for which cause is less certain, namely, those of the large bowel, breast, cervix uteri, and prostate. One might imagine that in a logical world there would be a major investment in the study of risk factors for these tumours. Yet, a survey conducted by the International Agency for Research on Cancer (IARC) showed that the sums spent on descriptive and analytical epidemiology compared to other forms of cancer research have hitherto been trivial, frequently less than 1% of national cancer research budgets (32). Some institutions, nevertheless, devote a larger share of their funds to epidemiology, about 5% for the US National Cancer Institute and close to 45% for the IARC. There are other constraints. The induction period of cancer is a major obstacle to epidemiological progress. Although in a sense very welcome, in that most forms of human malignancy seem to require continued exposure for a prolonged period, this phenomenon nonetheless poses major logistic prob lems in mounting prospective cohort studies and assessing the effects of intervention. The unique ability of prospective studies to enroll subjects at the period most critical for cancer etiology, for example, at puberty, to study subsequent breast cancer risk cannot be overemphasized, as many of the possible risk factors, e.g. hormone levels or body fat mass, cannot be measured retrospectively. Yet, the long waiting period not only gives rise to problems of follow-up but also permits other exposures the opportunity to exert an effect. Epidemiology is seen as painfully slow and rather imprecise and, further, has acquired a reputation of being expensive. Actually, if one considers the time scale involved, the contrary is true. The golden age of epidemiology, with large relative risks readily interpret able in causal terms, such as those associated with prolonged use of tobacco and the hepatitis B carrier state, is reaching an end. Increasingly, the relative risks uncovered are in the order of 1.5 to 2.5, an order of increased risk that could well be due to some undetected, unrecognized bias or confounding.


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Even comparatively large studies may not be large enough to yield sufficient cases in small subgroups of interest. To this end, it is imperative that a substantial portion of case-control studies be multi-centered and follow a common core protocol, as the IARC-coordinated SEARCH Programme (23), the study of bladder cancer coordinated by the US National Cancer Institute ( 18, 22), and those mounted by MacMahon and colleagues (28) with WHO support for breast cancer. This approach, increasingly used in controlled clinical trials, has many advantages. The planning phase, in which ex perienced investigators from several centers meet, ensures that all hypotheses are considered, even though they may not be fully examined. The multiplicity of centers ensures that sufficient cases are available for a pooled analysis. If there is a consistent increase in risk following some exposure in all or most of the study centers, then one has a greater confidence that the result is not likely to be due to bias or confounding, as it is unlikely that these factors would operate in the same way in all the centers. Given the variety of dietary items and the dishes in which they appear across continents and cultures, the emergence of a common constituent such as saturated fat or fiber as a risk factor would be more likely to carry etiological significance. While the increasingly popular meta analysis of published studies can be rewarding, a multicenter study with a common, agreed protocol is less liable to distortion and the problem of missing data (4, 14). If transplacental exposures prove to be of importance, rigorous monitoring of pregnancies will be needed. The sheer logistic effort would be enormous. Because many cancers would be likely to appear after the death of the mother, records would have to be kept for a very long time. Exposures from the mother would be further influenced by those after birth. Preservation of maternal DNA so that adducts could be examined on a case-control basis would seem to be a feasible solution. There is increasing concern about low-level exposures of whole pop ulations (e.g. air pollution), but the effects of such exposures are very difficult to assess. Imagine trying to show that cigarettes cause lung cancer in a population in which everybody smokes two per day.

DISCUSSION Wynder (52), writing on "Some Practical Aspects of Cancer prevention," quoted from an article by Ewing (9) on "Prevention of Cancer" as follows: "Though a great body of clinical infonnation shows that many forms of cancer are due to preventable causes, there has been little systematic research to impress this fact on the medical profession and to convey it to the public." Wynder then continued, "This was true then, as it is today, even though the history of environmental cancer-and thus of cancer prevention---dates back



151

to as far as 1775 to Pott's observation on the high incidence of scrotal cancer among chimney sweeps. " We make no apology for further citing and commenting on a section of Wynder's paper entitled "Methods of Prevention . " "There are three broad approaches to cancer prevention, the first and basic one is concerned with elements of cellular predisposition or resistence to cancers. " It is here that basic scientists are now exploring oncogenes, genetically controlled enzyme activity influencing oxidative and other forms of metabolism and the like, although it is not yet obvious how these can be manipulated to reduce risk. Nonetheless, the identification of susceptible individuals may be useful (see above). Although epidemiology must evolve to take advantage of new laboratory techniques, the final arbiter of success in prevention is perhaps the most basic of all epidemiological measures-the frequency and distribution of the dis ease. "Secondly, cancer prevention is of importance in regard to the early recognition and adequate handling of precancerous lesions. Extensive knowl edge about the course of such lesions plays a significant part in the prevention of numerous cancers. " Here there have been signal successes for cervical cytology such that in Finland, mortality rates have been convincingly shown to have fallen among those screened ( 17). Screening for oral precursor lesions has succeeded in a few parts of India and Sri Lanka; screening for post menopausal breast cancer and colonic polyps has reduced mortality some what, but not for lung cancer. "Thirdly, prevention concerns environmental cancers in which an ex ogenous factor or a group of factors play [sic] an important part and without which many of these tumors might not occur. " It is here that the major epidemiological research effort has hitherto been made. "Preventive measures in regard to these tumors seem to be more readily available, although the basic mechanisms of their cause may not be apparent. " One may well ask whether any serious effort at prevention has been made-a question discussed below . Wynder then reviews the incidence, suspected etiological factors, and experimental evidence; evaluates then current knowledge; and suggests pre ventive measures for a series of common cancers. The interested reader is referred to the original publication for a precise description (52). Most of the review is still relevant today, with some exceptions. Among the causes known today that were not listed by Wynder are biological agents such as the Epstein-Barr, Hepatitis B, and human papilloma viruses, and reproduction-associated factors such as age at first full-term pregnancy or first coitus. The role of diet, notably fiber, was not mentioned. Considerable space was devoted to the role of syphilis in head and neck cancer, but this may have been due to confounding with tobacco and alcohol . By 1952, several o f the major causal or risk factors for cancer were already


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known, although some of the suggestions in Wynder's table have not stood the test of time, e . g. for stomach cancer. Epidemiologists and laboratory scientists have since joined forces-a mar riage that has resulted in such hybrid disciplines as metabolic epidemiology (53) and molecular epidemiology (39, 40). The advent of techniques to measure medium-term exposures, e.g. albumin-bound aflatoxin and assays such as urinary cotinine to provide objective measures of exposure to environ mental tobacco smoke-have been immensely useful in characterizing ex posures and permitting their stratification in quantitative terms. Epidemiolo gists, however, have perhaps not been sufficiently aware of the imprecision attached to some of the laboratory measurements, imprecisions recognized by those working at the bench (6). The resulting misclassification of exposures may have distorted epidemiological conclusions. Some Goals for Health: Dream or Reality?

More than 35 years later, how have the prospects for prevention changed? 2000 is an attractive, round, almost magical number and this may be one of the reasons that several national and international bodies have chosen to set goals for prevention by that date. On a global scale, the best known goal is the World Health Organization'S (WHO) aim of "Health for All by the Year 2000." Despite the utopian aspect of such an ambitious target, it has allowed considerable progress to be made in a timescale shorter than likely otherwise. For cancer, substantially different goals have been set by various bodies . The most ambitious goal is that of the National Cancer Institute (NCI) in the US to reduce cancer mortality by half by the year 2000 (15) through primary and secondary prevention and im provements in treatment. More modest are the goals of WHO, the European Regional Office of the World Health Organization (EURO) , and the European Economic Community (EEC) to reduce cancer mortality at least 15% among people under 65 in the European Region . Prospects for Prevention

Prospects for prevention are reviewed here under the three classical headings of primary , secondary, and tertiary prevention. Whereas primary and second ary prevention are in the realm of the public health specialist, the third domain belongs more to the clinician and therapist, and is mentioned only briefly. Primary Prevention

Primary prevention represents the ultimate aim of the public health worker, as well as providing confirmation for the scientist of a suspected etiologic link between an exposure and a disease. The influence of the removal of the


153

handle of the legendary water-pump in London on the pattern of cholera cases was quickly seen. In cancer epidemiology, not only are the results longer to appear but the advent of new risk factors may blur the picture. Rarely has a single agent been found to be the sole factor responsible for the occurrence of a given cancer. Nonetheless, it is the epidemiological method that identified what may be considered the most widely disseminated and theoretically completely removable cause of cancer: tobacco use. Tobacco is a remarkable product when one considers the wide spectrum of


diseases to which it can be reliably linked as a causal agent. As early as the seventeenth century, several physicians and legislators had seen the need to combat smoking; unfortunately, economic considerations prevailed, and it was felt more profitable to tax tobacco than to ban it

(27).

The link between lung cancer and cigarette smoking was strongly es tablished as early as

1950, based on excellent epidemiological studies. Since

that time, hundreds of investigations have been done in various populations and countries, and they have repeatedly confirmed the earlier findings. It seems almost inconceivable that almost 40 years later there are still smokers, especially when one considers the fear of cancer in the general population, the low five-year survival rate among lung cancer victims, and the suffering experienced by cancer patients. Despite widespread recognition, probably even by the tobacco industry, that tobacco is the truly universal poison, few governments have seriously tackled this problem, a notable exception being the concerted effort by health educators, the health services, and the treasury in Norway

(5). Some sectors

of society have taken account of the links and have reduced consumption. Smoking in many developed countries is now largely a lower socio-economic class habit in males. The status of females is more complex. As noted above, the fall by

1% a year in tobacco consumption in developed countries is more 2% a year in the developing world. The tobacco

than offset by the rise of

peddled there is of the high tar/high nicotine category, both carcinogenic and addictive. WHO has stated that to discourage smoking would be the single most effective step to improving health. The NCI also considers smoking reduction a very important means of achieving some control of cancer mortality. Yet, the abolition of tobacco will not be painless. WHO asked the Food and Agriculture Organization of the United Nations (FAa) to study the social and economic gains that derived from the cultivation and production of tobacco as an agricultural crop. The reply

( 10), "The Economic Significance of Tobac 1977-1980,

co," concludes that "until world demand, which was still rising in

can be curbed sufficiently to make tobacco growing less profitable, it will be very difficult to induce growers to curtail production." The FAa predicts that world leaf tobacco output would increase annually by about

1.9% to about 7.0

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million tons in

1995, and around 8.5 million tons by the year 2000 (29). It is

not only the farmer who benefits; the tax revenues from the sale of tobacco are enormous

(10).

The costs of cancer have been estimated for several countries. In Scotland

(43) in 1976 there were 18,600 new cases of cancer. Including prevalent cases, the treatment costs were 33.4 million pounds sterling: lung cancer and breast cancer accounted for 17% and 12% of expenditure, respectively. Given such figures, it is not surprising that the first two main recommendations in


this report relate to smoking and the fifth to the development of cancer epidemiology. Yet in

1976, the revenue from tobacco in Scotland was 180 million pounds sterling, over five times greater than the direct costs for treating all cancers. The indirect costs would probably be

probably around

substantially greater, conservatively estimated in the US to be about three times those for short-stay hospital care and physician services combined. A study conducted in Northern Ireland

(46), however, the home of a substantial

portion of the UK tobacco industries manufacturing process, showed quite clearly that when all costs to society were considered (including health care costs, number of working days lost annually because of smoking, fires caused by tobacco, etc), there was a net loss to the community of around

103 million

pounds. When this was grossed-up to UK figures, the net loss was stagger ing. Arguments about health risks and lost lives seem to have little weight. The words of Disraeli, "the health of the people is the foundation upon which their happiness and all their power as a state, depends," seem to have been forgotten. The epidemiologist is excluded from the decision making process. Economic and industrial decisions are taken without knowledge of possible health consequences

(44).

From an ethical point of view, decisions to combat smoking should be made independently of potential benefits or costs. Human lives have to be saved and tobacco elimination would be a sensible way of achieving such a goal. Therefore, smoking cessation programs should help smokers escape their addictive habit and, even more important for the long-run, special efforts should be made to prevent the onset of smoking among children and adoles cents. The effects will not be seen until well into the next century, but programs have to be started now. Hakama et al

(1986) examined the likely 20 years

effect of a series of changes in smoking habits in Finland. Some

would need to elapse following abolition before rates in the population fell to those of nonsmokers. Postponement of the starting age for smoking by

20

years would have virtually the same effect. Long-term intensive health educa tion curricula such as the Know Your Body Program seem to be successful

(49). By contrast, very limited and isolated interventions do not work and should not be repeated.

CANCER CONTROL IN THE

1990s

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Attempts at intervention in a rural population (Emakulan District) in the State of Kerala, South India, involved

12,212 tobacco chewers and smokers

followed annually over five years. These persons were encouraged with personal and mass-media communication to give up their tobacco habits. Stoppage of the tobacco habit was substantially higher in the intervention group

(9.4%) compared to the control group (3. 2%). The intervention was

considered to be more effective among male chewers and those with a habit of long duration, groups who rarely quit their habit without intervention. This


effort was both personnel- and time-intensive and the results meager. The only method that would appear to be effective would be to make the habit prohibitively expensive. This would undoubtedly lead to clandestine produc tion and smuggling. ALCOHOL

Alcohol is another risk factor to be accorded high priority. Not

only has its abuse been causally linked to oropharyngeal and esophageal cancers (and perhaps breast cancer), but it also takes a heavy toll through accidents and violent deaths. Here, too, economic interests have long pre vailed. To effectively address this issue, comprehensive programs will be needed and, given that their aim is to promote a healthy life, they would be best combined with the anti-tobacco interventions. DIET

Given the present state of scientific knowledge on the relation between

diet and cancer, it is still difficult to propose preventive measures other than of the most general nature, possibly best summarized by the familiar adage "a

little of what you fancy does you good" and the exhortation "Come on child, eat your vegetables." The dearth of prospective dietary studies is a major gap in our knowledge; it is possible that these would uncover end-stage aspects of carcinogenesis rather than initiating events. Yet little is known about the normal physiological biochemistry of digestion. The use of new techniques such as the magnetic trapping microcapsule

(41) will certainly yield much

information and perhaps suggest where the cycle leading to carcinogenesis can best be broken. In the meantime, it would be reasonable to recommend an increased intake of fresh fruit and cruciferous vegetables, a reduction of animal fat, and the need to control one's weight. No harm will result from such a diet, and its effect on cancer and cardiovascular risk would probably be beneficial, although the magnitude of the reduction in risk cannot be precisely quantified. Wahrendorf

(48), in a most illuminating paper, has attempted to do so by

assessing the likely effect of shifting consumption of risk items between tertiles. This approach, however, ignores the fact that it would be very rare for a dietary item to be independent of others. Reduction in consumption of "x" will almost always entail changes in the intake of "y" and "z."


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Government frequently seems as reluctant as industry to influence the composition of foods, although specific examples exist of introduction of changes in food supply during some intensive programs, such as in North Karelia. Norway is one of the few countries to have a national dietary policy. Yet when the media draw the attention of the public in a consistent and non-sensationalized manner to the advantages of, for example, an adequate intake of dietary fiber, the public eventually responds and industry rapidly finds that it is able to produce high fiber foodstuffs at a profit. The (subsi dized ?) distribution of fresh fruit and vegetables could certainly do no harm and would probably reduce stomach, large bowel, and perhaps breast cancer. Most of the regulation of food today relates to additives and pesticides, not the nutrients. It would seem rational to avoid exposure to chemicals shown to be mutagenic or carcinogenic to the experimental animal, even though exposure to mutagenic substances in a normal diet is likely to be greater (2) than that from additives and pesticides. Results of diet modification could also conveniently be evaluated through randomized trials in selected populations and for a few specific endpoints (for example, dietary intervention following diagnosis of dysplastic breast dis ease) or through prospective cohort studies in populations undergoing impor tant changes in dietary habits (for example, countries becoming more affluent or migrant groups in, for example, Australia). To date, only one rigorously controlled randomized intervention has been attempted for esophageal cancer, in thc north of China (35). Although it may be too early to see whether administration for just over a year of retinol, riboflavin, and zinc influences long-term esophageal cancer risk, the initial results did not appear promising. Though prescription is more likely to succeed than proscription, the results of other vitamin A and analogue chemoprevention trials remain to be assessed. The substantial burden on medical care measures due to non melanoma skin cancer is often forgotten, possibly because survival is virtually 100%. The inexorable rise of some 3-6% per annum in malignant melanoma of skin in fair-skinned populations is of considerable concern. Yet both forms of cutaneous malignancy seem to be linked to exposure to ultra-violet light mainly of solar origin. Although there are inconsistencies in the evidence, the former is associated with chronic sun exposure, the latter to episodes of sunburn, frequently in childhood, and to the number of palpable naevi (the genesis of the latter is still obscure). For malignant melanoma, sunburn in childhood seems to be very important, as studies of migrants from Europe to Australia have shown. The risk of superficial spreading melanoma in those migrating after the age of 20 was about that of the home country-the risk in those migrating in early childhood was that of their Australian-born peers.

SUNLiGHT

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Protection against excessive sun exposure should reduce the burden of these cancers substantially. Campaigns, as in Australia ("Slip on a shirt, slap on a hat, slop on sun protection cream: between 11 and 3 slip under a tree") seem to have resulted, if not in a fall in incidence, at least in an increasing proportion of thin, hence better prognosis, lesions. The public perception of these messages is now being evaluated. Public apprehension concerning ionizing radiation is likely to ensure stricter control of exposures, although these for most are likely to be significantly lower than those experienced in certain homes due to radon. Radiation from medical sources is likely to diminish .


RADIAnON

VACCINATION The last domain for potential primary prevention relates to vaccination. The discovery of high relative risks, around lOO-fold , for pri mary hepatocellular carcinoma in hepatitis B carriers and the production of plasma-derived and recombinant vaccines gives hope that this form of cancer, currently responsible for 250,000 new cases a year, can be controlled. Trials are under way in The Gambia, West Africa (12, 13). The time scale involved is significant: some 30--40 years will be needed to show an effect. It is paradoxical that while this is an acceptable delay in, for example, forestry studies, it is difficult to obtain funding for such periods for health research . The role o f HTLV I in Western Japan and Eastern China, the association of the Epstein-Barr virus with nasopharyngeal cancer in South China and with Burkitt's lymphoma in Africa, and the possible link of cervix uteri cancer and several strains of the human papilloma virus suggest the possibility of preven tion by vaccination. Problems of evaluation of the effect of a vaccine, however, admirably discussed by Higginson et al (20) as long ago as 1971, including questions of safety, antigenicity, and time and mode of delivery, remain to be solved for most such potential vaccines.

Special note should be taken of the develop ing countries, where two thirds of the world's population lives. Although it will be several decades before the age structure is such that older people, i.e. those likely to get cancer, predominate, there seem to be two trends that militate against prevention. The first has already been mentioned: the gradual "Westernization" of diet, with an increasing intake of animal fat, as nations become more prosperous. Exhortation to avoid the mistakes of the more prosperous countries are not likely to succeed and may be resented. The second trend lies in industrialization. The importation of dangerous processes, abandoned or prohibited elsewhere, the failure to maintain plants, and the proliferation of small artisanal industry are likely to result in a burden of occupationally linked cancers. The safe use of insecticides and pesticides THE DEVELOPING COUNTRIES

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requires more than labeling of the container; it also requires the ability to read, the availability of protective clothing, and the will to accept the discipline involved in safe handling. Yet the number of such cancers is likely to be small compared to those caused by the ravages of tobacco. THE ROLE OF THE MEDICAL SCHOOL

An already existing institution, the

medical school, may play a seminal and crucial role in the implemention of


some of these preventive strategies. The authors are not in a position to know whether information on causation and prevention of cancer is more systematically imparted in medical schools than it was in the time of James Ewing. Tubiana

(45) noted that at a

competitive examination for staff positions in a Paris hospital, a question was posed on the factors causing cancer. Some of the candidates did not mention tobacco,

30% mentioned it in passing, usually as part of a long list of 38% described the cancer produced by the

chemical compounds. In contrast,

rubbing of the bit against the angle of the mouth in the horse. The examining board felt that more than a third of the candidates had no idea of the real role

1.5% of the papers. Occupational disease was practically ignored, apart from ionizing

of tobacco. The notion of an epidemiological enquiry appeared in but

radiation, for which the dangers were greatly exaggerated. The authors of the report were very disturbed by the findings-all the more so as many of the successful candidates would eventually be involved in student teaching. Tubiana states that the general practitioner of medicine is, or rather should be, the focus of all preventive action against cancer. Without his active participation and a deep conviction on his part, we cannot hope for action. The information brought to the public by the media does not have an impact unless it is confirmed by those in whom the public has confidence, such as the family doctor. Yet, in France,

57% of doctors smoke, a frequency greater (48%). Even more serious, a

than that for the male population as a whole

comparable percentage was found among medical students. In a pan-Australian survey

(19), participants were asked to state their main

source of information on health and lifestyle. The orthodox health pro fessionals (doctors and nurses) were the most frequently cited sources; women also reported obtaining information from magazines. Reliance upon the print

media was positively correlated with educational attainment, whereas reliance upon doctors and nurses was strongly inversely related to education. The whole ethos of the medical school is disease, its diagnosis and treat ment. The concept of prevention by and large is ignored.

Secondary Prevention Knowledge of the etiology of most common cancers is still quite

poor.

Fortunately, for some sites, an impact on cancer incidence and/or mortality through screening is possible.


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Although the incidence of cancer of the cervix uteri seems to be falling in all parts of the world, it still remains the leading cancer site in women in the developing world, with 370,000 cases estimated to have occurred in 1980. The success of a planned cervical cancer screening program with national coverage and a defined screening policy, i.e. population-based screening rather than self-selected screening, has been resoundingly demonstrated in Finland. Reasons for failure are discussed by Chamberlain (8). All successful programs have made a positive effort to recruit women into the system. It has been shown that most of the difference in social class among those who take up screening is eliminated by personal invitations to participate, thus indicat ing that lack of knowledge of the service is an important, and correctable, reason for failure to use it (2 1). Inadequate management of abnormalities detected can seriously affect the success of a screening scheme. Chamberlain states, "Resources for the development of screening programmes should be put primarily into methods for reaching the target population and secondly into ensuring adequate follow-up. Only when an acceptable participation level and foHow-up system have been achieved should improvement in sensitivity assume priority. It remains to be seen whether the necessary infrastructure in many parts of the world to support such a worthwhile preventive activity will be created. The highly successful use of specially trained paramedical workers in Sri Lanka to detect oral precancerous lesions in a joint WHO national program (50,5 1) was in another sense a failure, because the infrastructure necessary to further evaluate and to treat the lesions detected was inadequate. Screening for breast cancer by mammography has also been shown to be effective, at least among women older than 50 years of age. A reduction of 20% to 40% in mortality has been consistently reported. Nation-wide pro grams should be mounted, at least in all countries in which breast cancer represents a major cancer site among women. The case for screening for colon cancer, although less clear, certainly warrants considerable attention, whereas some screening programs, for ex ample, lung cancer, are very hard to justify as the gain for major expense is minimal. "

Tertiary Prevention The issue of improved methods of treatment and of prevention of recurrence are beyond the scope of this review. Suffice to say that progress in this field is slow and, at least according to certain authors, not commensurate with the investment in research and therapy (3, 1 1). For the common cancers such as stomach, lung, breast, ovary, and large bowel, in contrast to choriocarcino ma, testicular cancer, acute childhood lymphocytic leukemia, and Hodgkin's disease, five-year survival has improved little.

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CONCLUSIONS Cancer prevention is bedevilled by concepts of "them" and "us". Many societies today expect governments, i.e . "them," to ensure that citizens are provided with adequate amounts of risk-free food, air, and water and the ability to purchase safe products made in a safe workplace. They seem less willing to accept a measure of personal responsibility for their own health through their personal habits (see below). Yet, this neat dichotomy between community and personal responsibility is too simplistic by far. Personal habits are determined by peer example, advertising, educational level, socio economic level, and the like�lements partially open to governmental in fluence. McKeown's (30) thesis is that most of the major advances in the control of infectious disease in the nineteenth and twentieth centuries were the result of governmental action rather than progress in medical science. Better nutrition resulting in better immune status followed by vaccination, as well as better housing with improved water supply and sewage, were the reasons for success rather than antibiotics. Would this line of argument be applicable to cancer prevention? Would prohibition of tobacco and alcohol work? Would the removal of butter, cheese, and beef from the supermarket shelves be successful? History suggests not. Differential taxation might be effective, through reducing the ability of popUlations as a whole to indulge in harmful personal habits and foodstuffs. Many would feel such coercion abhorrent. Attempts by government to assist the population to avoid dangerous personal habits are not always welcome. In an Australian study (19) of a random sample of population all over the country, respondents were asked how much control they had over their own health. Only 10% considered that they had "little" or "almost no" control, 24% said they had "some" control, and a majority (70% of women and 61 % of men) said they had either "a lot of' control or "almost complete" control. Neither age nor income bore any clear-cut relationship to the response . Level of formal education did. Asked to select which six changes would most improve their future health, 18% said "better diet," 26% "more exercise," 17% "stop or reduce smoking, " 3% "reduce alcohol consumption," 12% "cope better with stress ," and 23% said that no change was needed . Men and women gave similar answers; slightly more men referred to smoking and alcohol, while slightly more women referred to diet and exercise. When asked to pick out the lifestyle or behavior pattern responsible for most health problems in Australia, 25% nominated alcohol abuse, 23% the abuse of legal or illegal drugs, and 23% poor diet. Insufficient exercise was mentioned by 14%, while 13% considered smoking the main health problem. This information is of great interest. Most important is the awareness of a


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majority that they had considerable control over their own health. In other words they accepted some degree of personal responsibility for their health. Tobacco, alcohol, sunlight, and industrial exposures apart, has the time come to abandon trying to apply what,we think we know and invest our time in finding out more about causation (epidemiology) and devising methods to persuade the public to heed our message, when we have one in which we are confident? Such efforts will need to be culture-specific and aimed at different age-groups and socio-economic strata. What induced the US public to become less and less tolerant of smoking in public places? Can these pressures be transferred to other cultures and other exposures? Those participating in the Australian survey mentioned above were asked why they had not made the change that they considered would most improve their own future health, about one quarter said they were too lazy and another quarter said they had no time, 1 7% considered it too hard, 1 2% said they were unsure how to go about it, 10% were not convinced it was worthwhile, and 9% said they lacked the facilities, money , or social support. The knowledge was there-the will to change apparently was not. Given that in this survey doctors and nurses were the major source of information on health and lifestyle for the less educated, the importance of personal contact and counsel ing is likely to be very great. It is likely that in the next 50 years , basic science will have uncovered much of the mechanisms of carcinogenesis. What has emerged to date seems incredibly complex, much more so than, say, particle physics, and if there are many paths between initiation and transformation, and from transformation to progression, it may not bc possible to devise methods to block a sufficient number of these avenues to prevent carcinogenesis. The unanswered basic question is why it should be that in a world where many cultures have aphorisms such as "a stitch in time saves nine" and "prevention is better than cure," and in which the value of prevention for infectious disease has been resoundingly demonstrated , so little is done for cancer. Is it because the public, and those they elect to legislatures, are still mesmerized by that elusive will-of-the-wisp--the cure for cancer? Literature Cited I . Adams,

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Nutrition: prospects for the 1990s.

Injury prevention and control: prospects for the 1990s.

Child health in the United States: prospects for the 1990s.

Prospects for ancillary treatment of sinusitis in the 1990s.

Setting the national agenda for injury control in the 1990s.

The future of public health: prospects in the United States for the 1990s.

Cancer of the cervix: prospects for immunological control.

Setting the national agenda for injury control in the 1990s.

Hospital cost containment in the 1980s. Hard lessons learned and prospects for the 1990s.

Setting objectives for public health in the 1990s: experience and prospects.

The infection control practitioner: an action plan for the 1990s.

Invasive cervical cancer in the 1990s.

A review of the prospects for the control of cancer through screening.

Oral contraceptives and gynecologic cancer: an update for the 1990s.

Lowering death rates from colorectal cancer: challenge for the 1990s.

Prospects for the control of sheep blowfly strike by vaccination.

Prospects for MEK inhibitors for treating cancer.

Asylum for psychiatric patients in the 1990s.

Separation techniques for biotechnology in the 1990s.

Toxicology in the 1990s.

The prospects for imaging lymph nodes in breast cancer.

Immunotherapy for lung cancer: advances and prospects.

Forces of change in the health care system. Implications for cancer care in the 1990s.

Tuberculosis control and research strategies for the 1990s: memorandum from a WHO meeting.