1. Do not smoke.Smokers, stop as quickly as possible and do not smoke in the presence of others.If you do not smoke, do not try it.
2. If you drink alcohol, whether beer, wine or spirits, moderate your consumption.
3. Increase your daily intake of vegetables and fresh fruits. Eat cereals with a high fibre content frequently.
4. Avoid becoming overweight, increase physical activity and limit intake of fatty foods.
5. Avoid excessive exposure to the sun and avoid sunburn especially in children.
6. Apply strictly regulations aimed at preventing any exposure to known cancer-causing substances. Follow all health and safety instructions on substances which may cause cancer.
More cancers may be cured if detected early.
7. See your doctor if you notice a lump, a sore which does not heal (including in the mouth), a mole which changes in shape, size or colour, or any abnormal bleeding.
8. See your doctor if you have persistent problems, such as a persistent cough, persistent hoarseness, a change in bowel or urinary habits or an unexplained weight loss.
9. Have a cervical smear regularly. Participate in organised screening programmes for cervical cancer.
10. Check your breasts regularly. Participate in organised mammographic screening programmes if you are over 50.
Revised following EC Cancer Experts Meeting in Bonn 28-29th November, 1994
Incorporates observations and comments of the Committee members who prepared the 'European Code Against Cancer'.
revised September 1994
revised December 1994
revised February, 1995
The European Code Against Cancer was originally drawn-up and endorsed by the high-level Committee of Cancer Experts in 1987. The Commission invited the European School of Oncology to assemble a group of international experts to examine and consider revision of the scientific aspects of the recommendations given in the current Code. This exercise took place and a new version was adopted by the Cancer Experts Committee at its meeting of November 1994. The revised Code will be the theme for the European Cancer Week 1995.
In the European Union in 1990 it is estimated that there were 1,292,000 incident cases of all forms of cancer excluding non-melanomatous skin cancers diagnosed: this burden was shared almost equally by each gender with 647,000 new cancers in men and 645,000 incident cancers in women.
Although the burden was equally shared, the forms of cancer which were the most common in men and women differed. In men, the major forms of cancer were lung cancer (141,500 cases), cancer of the colon and rectum (80,200), cancer of the prostate (76,100) and stomach cancer (46,700). In women the major forms of cancer incidence were breast cancer (157,000), cancer of the colon and rectum (89,200), lung cancer (33,900) and stomach cancer (33.800). In contrast to stomach cancer, which shows a downward trend in its occurence, all other cancers are still increasing with the exception of lung cancer where the risk appears to have stabilised in some countries among younger men.
Within the European Union considerable differences in cancer occurrence do exist with noticeable overall differences evident for all major cancers in the southern countries such as Portugal, Spain, Italy and Greece. In these countries virtually all major forms of cancer demonstrate a lower risk (except for stomach which is higher) when compared to the northern countries.
Against this background of Cancer as an important Public Health problem which is the commonest causes of premature and avoidable death in the European Union, the European Code Against Cancer was introduced as a series of recommendations which, if followed, could lead in many instances to a reduction in cancer incidence and also to reductions in cancer mortality.
The European Code Against Cancer was used throughout Europe for six years before being revised by a group of cancer experts from throughout Europe: these are listed in the Appendix to this report. This revised version also took into account the advice, observations and recommendations of a large number of individuals and groups who had experience with using the original European Code Against Cancer. Below the scientific rationale for each recommended point of the European Code Against Cancer is outlined.
Certain cancers may be avoided and general health improved if you adopt a healthier lifestyle.
Any recommendation made to reduce cancer occurrence should not be one which could lead to an increased risk of other diseases. The ten recommendations which comprise the revised European Code Against Cancer should, if followed, also lead to improvements in other aspects of general health. It is also important to recognise from the outset that each individual has choices to make about their lifestyle some of which could lead to a reduction in their risk of developing cancer. These choices, and the rationale underlying their recommendation, are presented below.
Doll R and Peto R., The Causes of Cancer, Oxford University Press, Oxford, (1982)
Esteve J, Kricker A, Ferlay J and Parkin DM (eds), Facts and Figures of Cancer in the European Community, IARC, Lyon (1993)
Jensen OM, Estève J, Møller H and Renard H, Cancer in the Member States of the European Community in 1980, Eur. J. Cancer 26: 11671256 (1990)
La Vecchia, C., Lucchini, F., Negri, E., Boyle, P., Maisonneuve, P. and Levi, F. (1992), Trends of Cancer Mortality in Europe, 195589. I. Digestive Sites, Eur. J. Cancer 28:132-235.
La Vecchia, C., Lucchini, F., Negri, E., Boyle, P., Maisonneuve, P. and Levi, F. (1992), Trends of Cancer Mortality in Europe, 195589. II Respiratory tract, bone, connective and soft tissue sarcomas, and skin, Eur. J. Cancer 28:514-599
La Vecchia, C., Lucchini, F., Negri, E., Boyle, P., Maisonneuve, P. and Levi, F. (1992), Trends of Cancer Mortality in Europe, 195589. III Breast and Genital Sites, Eur. J. Cancer 28:927-998
La Vecchia C, Lucchini F, Negri E, Boyle P, Maisonneuve P and Levi F, Trends in Cancer Mortality in Europe, 1955-89. IV, Urinary tract, eye, brain and nerves, and thyroid, Eur.J.Cancer 28:1210-1281
La Vecchia C, Lucchini F, Negri E, Boyle P, Maisonneuve P. and Levi F, Trends in Cancer Mortality in Europe, 1955-89 V Lymphohaemopoietic and all cancers, Eur.J.Cancer 28:1509-1581
Levi F, La Vecchia C, Lucchini F and Boyle P. (1993), Cancer Incidence and Mortality in Europe, 1983-87, Soz Praventivmed 1993; Suppl. 3: S155-S229
Smans, M., Boyle, P. and Muir, C.S. (eds), Cancer Mortality Atlas of EEC, IARC Scientific Publication No 107, IARC, Lyon (1993).
It is estimated that between 25 and 30 per cent of all cancers in developed countries are tobacco-related (table 1). From the results of studies conducted in Europe, Japan and North America, between 83 and 92 per cent of lung cancers in men, and between 57 and 80 per cent of lung cancers in women, are attributable to cigarette smoking. Between 80 and 90 per cent of cancers arising in the oesophagus, larynx and oral cavity are related to the effect of tobacco, both acting singly and jointly with alcohol consumption.
Cancers of the bladder, pancreas, kidney, stomach and cervix are causally related to tobacco smoking and there have been suggestions of an association with cigarette smoking and an increased risk of leukaemia and colorectal cancer although the causal nature of these latter associations has not been accepted.
Because of the length of the latency period, tobacco-related cancers observed today are related to cigarette smoking patterns over two decades ago. Consequently, following any decrease in smoking prevalence there will be a period of time which will elapse before any decrease in the incidence of tobacco-related cancers becomes apparent.
There is now strong evidence of the adverse health consequences of Environmental Tobacco Smoking (ETS) sometimes referred to as passive smoking. On the basis of the available epidemiological data, the United States Environmental Protection Agency declared in 1992 that ETS was a proven lung carcinogen in humans.
The risk of lung cancer is increased in non-smoking women who have husbands who smoke tobacco. There also appears to be an increased risk of myocardial infarction due to exposure to ETS and the adverse health consequences in children whose parents smoke includes an increase in the frequency and severity of asthma and of upper and lower respiratory tract infections.
Tobacco can kill in over twenty different ways including causes such as lung cancer and other forms of cancer, heart disease, strokes and chronic bronchitis and other respiratory diseases. Smokers have three times the death rate in middle-age (between the ages of 35 and 69) than non-smokers and about half of regular cigarette smokers will eventually die from their habit.
Many of these are not particularly heavy smokers but they can be characterised by starting smoking in their teenage years. Half of the deaths from tobacco will take place in middle age (35-69) and each will lose approximately 20-25 years of non-smokers life expectancy: the remaining half of the deaths will take place after the age of 70. However, there is clear and consistent evidence that stopping smoking before having cancer or some other serious disease avoids most of the later excess risk of death from tobacco even if smoking stops in middle age.
It is estimated that world-wide, smoking kills three million people each year: the second half of the Twentieth century was notable in that there was estimated to have 60 million deaths caused by tobacco world-wide. In most countries the worst consequences of the Tobacco Epidemic are yet to come, particularly among women in developed countries and in populations of developing countries, since by the time the young smokers of today reach middle or old age there will be about ten million deaths each year from tobacco.
Approximately 500 million of the world's population today can expect to be killed by tobacco, 250 million of these deaths being premature and occurring in middle age.
The situation in Europe is particularly worrying. The European Union is the second largest producer of cigarettes (694 billion in 1993) after China (1,675 billion) and the major exporter of cigarettes (218 billion). In Central and Eastern Europe there is a continual increase in the smoking habit. Of the six World Health Organisation (WHO) regions, Europe has the highest per capita consumption levels of manufactured cigarettes and faces an immediate and major challenge in meeting the WHO target for a minimum of 80 per cent of the population to be non-smoking.
Currently (Spring 1994) in the European Union, 42% of men and 28% of women are regular smokers. The smoking prevalence in women is artificially lowered by the low rates reported in southern Europe where there is evidence that these rates are rising and seem set to continue to rise over the next decade. In addition, smoking prevalence in the age range 25-39 years is high (55 per cent in men and 40% in women) and can be expected to have a profound influence on the future cancer pattern. It is especially concerning that the smoking prevalence among General Practitioners, who play an exemplary role in health behaviour, remains high in many parts of Europe. This should be a target for immediate action.
It has been demonstrated that changes in cigarette consumption are affected mainly at a sociological level rather than by actions, such as individual smoking cessation programmes, targeted at individuals. Actions such as advertising bans and increases in the price of cigarettes influence cigarette sales particularly among adolescents. Therefore, a Tobacco Policy is necessary to reduce the health consequences of tobacco, and experience shows that this should be targeted via a variety of actions aimed to stop young people starting smoking and to help smokers to quit.
To be efficient and successful, a tobacco policy has to be comprehensive and maintained over a long time period. Increased taxes on tobacco, total bans on direct and indirect advertising, smoke-free enclosed public areas, education, effective health warning labels on tobacco products, a policy of low maximum tar and nicotine levels in cigarettes, encouragement of stopping smoking and individual health interventions have to be implemented.
The importance of adequate intervention is demonstrated by the low lung cancer rates in Scandinavian countries which, since the early 1970s, have adopted integrated central and local policies and programmes against smoking. In the United Kingdom, tobacco consumption has declined by 30% since 1970 and lung cancer mortality among men has been decreasing since 1980 although the rate remains high. In France, between 1992 and 1993 there has been an 3% reduction in tobacco consumption due to the implementation of anti-tobacco measures introduced by the Loi Evin.
Hence, the first point of the European Code Against Cancer is:
DO NOT SMOKE. Smoking is the largest single cause of premature death.
SMOKERS: STOP AS QUICKLY AS POSSIBLE. In terms of health improvement, stopping smoking before having cancer or some other serious disease avoids most of the later excess risk of death from tobacco even if smoking stops in middle age.
DO NOT SMOKE IN THE PRESENCE OF OTHERS. The health consequences of your smoking may affect the health of others around you.
IF YOU DO NOT SMOKE, DO NOT EXPERIMENT WITH TOBACCO. Most who experiment become regular smokers: it is difficult to stop once you have started.
Boyle P., The Hazards of Passive and Active Smoking, New Engl.J.Med. 328:1708-1709 (1993)
Bosanquet N., Europe and Tobacco,.BMJ 304:370-372 (1992)
Doll R, Peto R, Wheatley K, Gray R and Sutherland I., Mortality in relation to smoking: 40 years' observation on male British doctors, Brit Med Jour 309: 901-911 (1994)
IARC (International Agency for Research on Cancer) Monographs on the Evaluation of Carcinogenic Risks to Humans, Tobacco Smoking. Volume 36, IARC, Lyon (1986)
Joossens L, Naett C, Howie C and Muldoon A., Tobacco and Health in the European Union. An overview, European Bureau for Action on Smoking Prevention. (BASP), Brussels (1994)
La Vecchia, C., Boyle, P., Franceschi, S., Levi, F., Maisonneuve, P., Negri, E., Lucchini F. and Smans, M., Smoking and Cancer with Emphasis on Europe, Eur. J. Cancer 27: 94104 (1991)
Peto R, Lopez AL, Boreman J, Thun M, and Health Jr C., Mortality from tobacco in developed countries: Indirect estimation from national vital statistics, Lancet 339: 1268-1278 (1992)
Peto R, Lopez AL, Boreman J, Thun M, and Health Jr C., Mortality from smoking in developed countries 1950-2000, Oxford Medical Publications, Oxford (1994)
United States Department of Health and Human Services, The Health Benefits of Smoking Cessation, U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control, Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, DHHS Publication No. (CDC) 90-8416, 1990.
U.S. Environmental Protection Agency, Respiratory Health Effects of Passive Smoking: Lung Cancer and Other Disorders, Office of Health and Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency. EPA/600/6-90/006F, December 1992.
Alcohol drinking has not been demonstrated to be a carcinogen per se in animal experimentation, although there are data indicating that chronic oral ethanol ingestion may have a co-carcinogenic effect on tumours of the oesophagus and possibly of the non-glandular fore-stomach induced by well-known chemical carcinogens in experimental animals.
In humans, there is convincing epidemiological evidence that the consumption of alcoholic beverages increases the risk of cancers of the oral cavity and pharynx (other than the salivary glands and the nasopharynx) and of the oesophagus, and larynx. The risks are essentially due to the content of ethanol in alcoholic drinks consumed, and appear to be linked to the most commonly used alcoholic beverage in each population. They tend to increase with the amount of ethanol drunk, in the absence of any clearly-defined threshold below which no effect is evident.
There is evidence that both alcohol drinking and cigarette smoking increases the risk of cancers of the upper digestive and respiratory tract, each factor approximately multiplying the effect of the other. Compared to never-smokers and non alcohol drinkers, the relative risk of these neoplasms is increased between ten and one hundred fold in heavy smokers and heavy drinkers. Indeed, in the absence of drinking and smoking, the risk of oral pharyngeal and laryngeal cancers in developed countries is extremely low.
Alcohol drinking increases the risk of upper digestive and respiratory tract neoplasms, even in the absence of smoking. This suggests that alcohol may facilitate the carcinogenic effect not only of tobacco, but also of other carcinogenic agents to which the human upper digestive and respiratory tract are exposed, particularly those of dietary origin. Although it has been suggested that alcohol derived from "strong" drinks is more deleterious for cancer risk at these sites, at comparable levels of alcohol intake, the evidence is inconclusive. Thus, the total amount or ethanol ingested appears to be the key factor in determining this increased risk rather than the precise source of that alcohol and it is total consumption of ethanol ingested which should be reduced.
Alcohol drinking is also strongly associated with the risk of primary liver cancer, although the relationship is more difficult to demonstrate in epidemiological studies, since most alcohol-related liver cancers follow a cirrhotic degeneration, which may itself have been caused by alcohol drinking and whose existence in an individual may well have lead to a subsequent reduction of alcohol drinking.
Epidemiologically, alcoholic drinking has also been linked to cancers of the large bowel in both sexes and of the female breast. Although the associations are moderate and hence open to discussion, since these are the two most common neoplasms in developed countries after lung cancer, even a small risk for alcohol drinking may have important Public Health implications.
The U-shaped pattern for alcohol intake distribution in relation to risk of cardiovascular disease, cardiovascular mortality and total mortality is well-known: this classic pattern is one of decreased risk in light drinkers compared to non-drinkers and then an increasing risk as alcohol consumption increases (figure 1). Nevertheless, the task of fixing a threshold on daily alcohol intake, below which alcohol drinking is definitely free from cancer risk (or, in other words, identifying the upper limit of completely safe regular alcohol consumption) is not simple. Factors such as sex, age, physiological conditions or dietary intake profile probably modify any such threshold.
There is some evidence showing that a daily alcohol intake as low as 10 grams/day (that is, approximately, one drink per day) may already be associated with some increase in breast cancer risk relative to non-drinkers: some studies suggest that this risk may be increased by between 30 and 50 per cent compared to non-drinkers. The lower limit associated with a significant risk of cancer at other sites (such as cancers of the upper digestive and respiratory tracts, liver or colorectum) is probably somewhat higher (about 30 grams per day) and this appears to be particularly true for men. Furthermore, alcohol drinking is sometimes associated with lower intake of certain potentially beneficial nutrients, such as those arising in fruits and vegetables.
All the above points should be considered to give sensible advice regarding individual recommended limits of alcohol consumption. These limits should not exceed between 20 to 30 grams of ethanol per day (i.e. about two to three drinks of beer, wine or spirits each day) and may be lower than this for women.
International Agency for Research on Cancer (IARC) Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 44. Alcohol Drinking, International Agency for Research on Cancer, Lyon (1988)
Doll R, Forman D, La Vecchia C and Woutersen R., Alcoholic Beverages and Cancer of the Digestive Tract and Larynx. In: Vershuren P.M. (ed.), Health Issues Related to Alcohol Consumption. pp 126-166, ILSI Press, Washington, 1993.
Doll R, Peto R, Hall E, Wheatkey K and Gray R., Mortality in relation to consumption of alcohol: 13 years' observations on male British doctors, Brit Med Jour 309: 911-918 (1994)
Marmot M and Brunner E, Alcohol and cardio-vascular disease: the status of the U-shaped curve, Brit Med Jour 303: 565-568 (1991)
Rimm EB, Giovannucci EL, Willett WC, Colditz GA, Ascherio A, Rosner B et al., Prospective study of alcohol consumption and risk of coronary disease in men, Lancet 338: 464-468 (1991)
There exists a large and consistent body of epidemiological evidence indicating a strong protective effect of higher intakes of vegetables and fruit on the risk of a wide variety of forms of cancer, in particular with lung, larynx, oropharynx, oesophagus, stomach, colon and rectum and pancreas. Analysis of the type of vegetables and fruits, whether raw and fresh vegetables and fruits, lettuce, carrots, leafy green and cruciferous vegetables, citrus fruits, broccoli and allium vegetables (garlic, onions, etc) consistently show a preponderant negative association with cancer risk. Pulses, sometimes referred to as legumes, though still showing a negative association, show the least pronounced effect.
A higher consumption of vegetables and fruits is consistently although not universally associated with a reduced risk of cancer at most sites, the association being most marked for epithelial cancers, in particular those of the alimentary and respiratory tract and weak to non-existent for hormone related cancers.
The consistent lower rates of many forms of cancer reported in southern European countries has been linked to The Mediterranean Diet: this is typically lower in total fat, particularly in fats from animal sources, and meats and higher in fish, olive oil, vegetables and fruits, fibre and grains. While strongly suspected that there is a link, this has not yet been proved satisfactorily.
The association with reduced risk of cancer exists for a wide variety of vegetables and fruits; in particular raw forms. There also exists increasing evidence that consumption of such higher levels is also beneficial for other chronic diseases. Vegetables and fruits contain a large number of potentially anti carcinogenic agents with complementary and overlapping mechanisms of action.
The preventable proportion for some major cancers is considerable although the exact molecule(s) in vegetables and fruits which confers this protection is unknown and the exact mechanism of action is unknown. Insight into the mechanisms of action is only partly available, but is not required for Public Health measures although it is not possible to recommend dietary supplementation with vitamins and minerals to reduce cancer risk based on the evidence presently available.
At the present time it is difficult to be precise about the quantity of fruits and vegetables necessary to confer this protection. Fruits and vegetables should be taken with each meal whenever possible. The National Cancer Institute in the United States has advocated a Five Servings per Day programme. According to this advice a serving refers from either consumption of salad as part of a meal or eating an apple as a snack. Similar actions in Europe could lead to a reduction in cancer risk.
Block G (1991), Vitamin C and cancer prevention: the epidemiologic evidence, Amer. J. Clin. Nutr. 53: 270-282
Blot WJ, Li J-Y, Taylor P, Guo W, Dawsey S, Wang G-Q, Yang CS, Zheng S-F, Gail M, Li G-Y, Yu Y, Liu B-q, Tangrea J, Sun Y-h, Liu F, Fraumeni JF, Zhang Y-H and Li B., Nutrition Intervention Trials in Linxian, China: Supplementation with Specific Vitamin/Mineral Combinations, Cancer Incidence, and Disease-Specific Mortality in the General Population, J Natl Cancer Inst 85: 1483-1492 (1993)
Garland M, Willett WC, Manson JE and Hunter DJ, Antioxidant micronutrients and breast cancer, J Am Coll Nutr 12: 400-411 (1993)
Steinmetz KA and Potter JD, Vegetables, Fruits and Cancer, Cancer Causes and Control 2:325-357 (1991)
Within this point there are two distinctive potential risk factors: obesity (or overweight) and high fat intake. Nevertheless, these factors are not completely correlated, because population differences in weight are not explained primary by fat intake. For this reason, we need to explain the evidence for both statements in an independent fashion.
Obesity has been shown to be an important cause of morbidity and mortality in general but it has to be kept in mind that different determinants of body weight, such as physical activity and total energy intake, may be at the same time associated with the risk of the development of certain disorders, including cancer.
Moreover, there is some evidence to show that tobacco use to strongly confounds epidemiological studies analysing the relation between relative weight and cancer and other disorders. Also, alcohol is an energy/bearing nutrient and excessive alcohol consumption has been associated with both cancer risk and higher relative weight. These comments are made to emphasise the methodological difficulties and the importance to control for confounding factors to isolate the real and precise effect of relative body weight or the fact of "becoming overweight" on the risk of cancer.
Other points that should be considered are the heritable component of obesity, and the highly significant correlation between Body Mass Index values in childhood and adulthood or, in other words, the likely existence of critical periods in childhood for the development of obesity. A practical message on avoiding become overweight could best be tailored to children or adolescents, trying to focus preventive efforts on these developmental stages.
There have been some systematic attempts to describe the pattern of cancer incidence and mortality in overweight individuals. The American Cancer Society followed a cohort of 1 million people and analysed the data arising from 750,000 volunteers who completed a detailed four page questionnaire including questions on height and weight. In this study an excess mortality was found from cancers of the colon and rectum, prostate, uterine corpus, uterine cervix, gallbladder and the female breast. Overall, individuals who were 40% or more overweight had a mortality ratio for cancer of 1.33 and 1.55, for men and women respectively. The second cohort study was carried out in Denmark, and included almost 44.000 obese persons whose cancer incidence was compared to that in the general Danish population.
Overall, the incidence was increased by 16% in the cohort of overweight individuals, and the main cancer sites affected included uterine corpus, pancreas, prostate, colon, oesophagus, liver, and breast among women above the age of 70. In younger women a decreased incidence of breast cancer was observed. Some of the mechanisms which could explain the effect of overweight, are possibly related to hormonal profiles (for breast and endometrial cancer), alcohol consumption (for cancer of the oesophagus and liver in the Danish study), and dietary habits (for cancer sites such as colon or pancreas).
There are also data which give some evidence implying that a total fat intake of over 40% calories may act as a risk factor for cancer of the colon, and prostate, and possibly somewhat for cancer of the pancreas, ovary, and endometrium. However, a previous postulate which apparently supported the message of dietary fat reduction, mainly the hypothesis that greater fat intake increases breast cancer risk, has not yet been proven in the main cohort and case-control studies.
Moreover, various types of fat (saturated, polyunsaturated, monounsaturated, or partially hydrogenated vegetables fats) may have different effects on the risk of cancer. Interestingly, there are some metabolic data, as well as the experience in Mediterranean countries within Europe, which suggest that the intake of a considerable proportion of energy as monounsaturated fat would not be harmful and might be in some cases beneficial.
In summary, the available evidence implies that a cutback in dietary fat intake over the ranges currently recommended is not likely to have a tangible and sustained effect on body fatness, whereas the recommended moderate reduction in dietary fat is likely to have little effect on cancer incidence, cancer mortality or total mortality. As for the preliminary evidence suggesting an inverse association between the level of monounsaturated fat in the diet and risk of cancer, further research is necessary before spreading a really established message. On the other hand, it may be conscious to support the underlying message on the benefits of avoiding becoming overweight addressed to the general population.
However, awareness of the connection between smoking and relative body weight is essential for clinical and public health practitioners attempting to modify unhealthy behaviours, and this seems to be particularly important in the smoking cessation efforts. Clues to healthy strategies to maintain body weight without falling back on smoking should be unambiguously formulated. It should also be emphasised that body weight reduction and fat intake limitation, especially the saturated fat component will not only help to prevent cancer but, would have beneficial effects on cardiovascular disease.
Albanes D, Jones Y, Micozzi MS, Mattson ME, Associations between smoking and body weight in the US population: Analysis of NHNES II, Am J Public Health 1987; 77: 439-44.
Boyd NF, Martin LJ, Noffel M, Lockwood GA and Tritchler DL, A meta-analysis of studies of dietary fat and breast cancer risk, Br.J.Cancer 1993: 68:627-636
Dietz WH, Critical periods in childhood for the development of obesity, Am J Clin Nutr 1994; 59: 955-9.
Garfinkel L, Stellman SD, Mortality by relative weight and exercise, Cancer 1988; 62: 1844-50.
Giovannucci E, Rimm EB, Colditz GA, Stampfer MJ, Ascherio A, Chute CC and Willett WC (1993), A prospective study of dietary fat and risk of prostate cancer, J Natl Cancer Inst 85: 1571-1579
La Vecchia C, Cancers associated with high-fat diets, Monogr Natl Cancer Inst 1992; 12: 79-85.
Lee IM, Manson JE, Hennekens CH, Paffenbarger RS, Body weight and mortality, JAMA 1993; 270: 2823-8.
Moller H, Mellemgaard A, Lindving K, Olsen JH, Obesity and cancer risk: a Danish Record-linkage Study, Eur J Cancer 1994; 30: 344-50
Must A, Jacques PF, Dallal GE, Bafema CJ, Dietz WH, Long-term morbidity and mortality of overweight adolescents. A follow-up of the Harvard Growth Study of 1922 to 1935, N Engl J Med 1992; 327: 1350-5.
Paffenbarger RS et al., The association of changes in physical-activity level and other lifestyle characteristics with mortality among men, N Engl J Med 1993; 328: 538-45.
Willett WC, Diet and health: what should we eat?, Science 1994;264: 532-7.
The incidence of skin cancer has increased dramatically this century particularly in Northern Europe. The most reliable statistics pertain to melanoma which has doubled in incidence every ten years in many countries. Indeed the rate of increase has exceeded that of any cancer except for lung cancer in women, although there is some evidence from the United States that the rate of increase may be slowing in younger cohorts. The annual incidence of malignant melanoma in the United Kingdom and Germany is now, for example 10 per 100,000 person years giving an approximate lifetime risk of 1 in 200.
Evidence has accumulated that the major aetiological factor for melanoma is excessive exposure to sunlight. The first major piece of evidence for this is that melanoma is essentially a disease of white skinned peoples (fair skin being more susceptible to the ill effects of sunlight ): the annual incidence of melanoma for example in Japan being only 0.2 per 100,000 person years. Furthermore, although the incidence of melanoma has increased annually in white peoples in Europe, the United States, Canada, Australia etc. there has been very little increase in incidence amongst pigmented peoples of African or Asian origin.
Second, there is a relationship between latitude and incidence of melanoma in white peoples. The incidence of melanoma for example is highest in countries like Australia (50 per 100,000 per annum) and in hotter regions of the United States such as Southern Arizona. Furthermore there is a relationship between the length of time that an individual has lived at lower latitudes and risk of melanoma, presumably representing lifetime accumulated excessive exposure to the sun.
Third, case control studies within Europe have identified intense intermittent exposure to the sun recreationally as a risk factor for melanoma. Several studies have for example identified high social class, indoor occupation, sunburn and sunbathing holidays as risk factors for melanoma reinforcing the view that at least in some populations the relationship between risk of melanoma and sun exposure is not a simple cumulative one.
The question of precisely what pattern of sun exposure is most harmful is not fully answered. The observations that at least in Northern Europe indoor workers get melanoma rather than their outdoor working compatriots along with the case control data above suggest that intermittency is crucial. That it is the cycle of being white in the winter, red in the spring and brown in the summer which is harmful. However, there is undoubtedly evidence, particularly from Australia that total cumulative overdosage of sunlight is also important. Sun induced non-melanomatous skin lesions such as basal cell carcinomas and actinic keratoses (which have a simple relationship with cumulative sun exposure) for example are significant risk factors for melanoma.
It is likely then, that the health education messages should be avoid sunburn and reduce your total cumulative dosage of sun exposure: the latter is another way of saying "don't tan". It is not clear either what exactly could be the benefit of sunscreen against the risk of melanoma: whereas it may be used to block certain types of ultra-violet light from reaching the skin (specifically ultraviolet B (UVB)), it may allow an increased exposure to other types which may be harmful (e.g. ultraviolet A and ultraviolet C).
Although the incidence of melanoma is still not very high in comparison to the more common tumours, a major aetiological factor in its causation has been identified. In Europe, the increase in incidence has been linked with the desire to be sun-tanned which has been fashionable since the 1930's. It would seem imperative that if the trend to increasing numbers of melanoma patients is to be reversed, then we have to reverse these trends. Use of artificial sources of Ultra-Violet (UV) exposure, such as sunbeds and ultraviolet lamps should therefore be similarly discouraged.
There is some evidence that excessive sun exposure is particularly deleterious in childhood and youth. Migration studies of emigrants to Australia and Israel have for example shown a significantly greater risk of melanoma for adults born there. Furthermore case control studies linking sunburn to risk of melanoma have (although not universally) identified sunburn under the age of 15 years as particularly significant. Finally there was some evidence from the only prospective study to address the subject, the United States Nurses' Health Study, that early excessive sun exposure was more significant in terms of risk of melanoma than sun in adult life. It is therefore necessary that the European Code should specially address the question of sun protection for children of all ages.
Armstrong B, Epidemiology of malignant melanoma: intermittent or total accumulated exposure to the sun?, J Dermatol Surg Oncol. 14: 835-849 (1988)
Khlat M, Vail A, Parkin M and Green A, Mortality from melanoma in migrants to Australia: variation by age at arrival and duration of stay, Am J Epidemiol 135: 1103-1113 (1992)
Osterlind A, Tucker MA, Stone BJ and Jensen OM, The Danish case control study of cutaneous melanoma. II Importance of UV- light exposure, Int J Cancer 42: 319- 324 (1988)
Roberts DL, Malignant melanoma in West Glamorgan: increasing incidence and improving prognosis 1986-1988, Clin Exp Dermatol 15: 406-409. (1990)
Scotto J, Pitcher H and Lee JAH, Indications of future decreasing trends in skin melanoma mortality among white males in the United States, Int J Cancer 49: 490-497 (1991)
Vagero S, Swerdlow A and Beral V, Occupation and melanoma: cancer registrations in England and Wales and in Sweden, Br J Indust Med 47: 317-324. (1990)
The message in this item of the code solicits responsible behaviour from individuals in three respects. First, from those who have to provide timely and clear instructions, i.e., chiefly legislators, regulators and educators in the public health and occupational health sectors, who are in charge of translating into sets of instructions in various forms (norms, recommendations, advice) the information on the risk of cancer from substances, or more generally, agents (physical, chemical, biological ) in the environment derivable from research results. Second, from those who should follow these instructions in order to protect the health of others, for instance, managers, hygienists and doctors in industry and in public authorities. Third, from every citizen who, in order to protect his or her own health, ought to pay heed to the presence of carcinogenic pollutants, especially in the working environment where they may be found more often and in higher concentrations than in the general environment.
The objective of reducing cancer occurrence through the control of environmental carcinogens rests on the fact that a substantial number of carcinogens, natural and man-made, have been - and continue to be - identified. The latest summary (March 1994) of the series "IARC Monographs on the Evaluation of Carcinogenic Risks to Humans" lists, out of 775 evaluated agents, 39 single agents or groups of agents, 11 mixtures of agents, and 13 exposure circumstances (all occupational) for which there is "sufficient evidence" of carcinogenicity in humans.
An additional 41 single agents or groups of agents, 5 mixtures and 4 exposure circumstances (3 of which occupational) are classified as "probably carcinogenic" to humans, whereas a total of 209 agents, groups of agents or exposure circumstances are classified as "possibly carcinogenic" to humans, largely on the basis of carcinogenicity data from animal experiments. The proportion of all cancers which can be causally attributed to carcinogens in the occupational and general environment, and are therefore wholly or partly avoidable through exposure control, is certainly not negligible, but remains difficult to quantify reliably, depending as it does on the variable prevalence of the exposures by geographical areas and periods of time as well as on the concurrent prevalence of other dominant cancer causing factors (typically tobacco smoking).
An estimated upper limit of 4% of cancers are attributable to the occupational environment although wide variations are found in this proportion when, for instance, lung cancer in relation to occupational exposures is examined in different geographical areas, pointing to the importance of local concentrations of cases susceptible to preventive control. On the other hand, agents in the general environment to which a large number of subjects are exposed for long periods, such as environmental tobacco smoke (passive smoking), though increasing only modestly the relative risk for certain cancers, may be at the origin of a sizeable number of cases, running into several thousands yearly in the European Union. It is essential that for any activity liable to present a risk of exposure, the nature, degree and duration of such exposure must be determined in order to define what measures need to be taken to prevent or reduce the exposure.
Among these measures, suitable operating procedures and methods are of an utmost importance. Instructions to be followed may take the form of quantitative control limits of exposure, derived empirically or through formal procedures, which still leave much to be desired, of quantitative risk assessment. In any case, the specification of a quantitative control limit for exposure in the general or occupational environment combines two elements: on one side the quantitative estimate of the risk associated with a given level of exposure and on the other the level of risk regarded as socially "acceptable" (by the parties involved in discussing the limit, e.g., regulators, representatives of the community, etc.) in view of the technical feasibility and human and economic costs of various degrees of control. Evidence is available that limiting the exposures to carcinogens in occupational environments has indeed been followed by a fall in cancer occurrence.
Council Directive 89/391/EEC of 12 June 1989 on the introduction of measures to encourage improvements in the safety and health of workers at work
Council Directive 90/394/EEC of 26 June 1990 on the protection of workers from the risks related to exposure to carcinogens at work
IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Lists of IARC Evaluations (Vol. 1-60), International Agency for Research on Cancer, Lyon, (1994).
Simonato L, Vineis P, Fletcher AC, Estimates of the proportion of lung cancer attributable to occupational exposure. Carcinogenesis, 1988: 2: 1159-1165.
Swerdlow AJ, Effectiveness of primary prevention of occupational exposures on cancer risk, In: Hakama M, Beral V, Cullen JW, Parkin DM (eds). Evaluating Effectiveness of Primary Prevention of Cancer, IARC Scientific Publication No 103, International Agency for Research on Cancer, Lyon, pp. 23-56 (1990).
These two points are potentially useful as secondary prevention and serve as reminders about different visual body signs or symptoms that could easily observed by anyone and that are possibly related to cancer. It is unequivocally established that cancer survival is better for early, localised disease than for the later stage, advanced form of the disease. Thus the earlier in the process that a cancer can be diagnosed and treated then the better this is for the patient. The purpose of these two recommendations is to ensure that potential symptoms of cancer are not ignored but serve as a clear warning for the individual to consult his or her doctor for advice. The signs and symptoms described are not specific for cancer. When any one is present, the individual should see a doctor.
The first sign of certain cancers in an individual can be the occurrence of unexpected bleeding: for example, blood in the stool, blood in urine, blood when vomiting or an unexpected bloody discharge from the vagina which could occur in the postmenopausal women. There are other common reasons why such bleeding could have occurred but it is always wise policy to have the reasons for the bleeding determined by a physician. It should be noted that screening for occult blood in faecal material is being evaluated at present as a method of screening for cancers of the colon and rectum and that cytological examination and the microscopic search for blood in the urine is commonly employed among certain groups of workers in the chemical industry.
Continuous or abnormal external bleeding from the nose, ears or sores, does not always suggest a cancer process at first glance. However, when those symptoms appear, a risk for an early process of cancer development should be considered.
Presence of a lump on one site or organ could indicate cancer development. A first approach could be an age-, organ and site specific oriented search for lumps related to cancer. The testes, thyroid gland, the neck, armpit and groin are organs and sites where lymph nodes are present and their enlargement could indicate the possibility of a process compatible with that of a lymphoma, a cancer of the soft tissue or of a metastatic process.
Among lymphomas the appearance of nodules are not always observed as a first symptom of this cancer, rather than a broad spectrum of non-specific symptoms. The detection of a lump in the breast of a woman should be referred to a doctor: methods of detection of such lumps are discussed in section 10 below.
Most melanomas are detected by the patient and self examination has the potential at least for early detection, not requiring expensive screening techniques. There is furthermore a considerable survival advantage in the early detection of melanomas. The prognosis of melanoma is tightly linked to the so-called Breslow thickness which is a measurement made by the pathologist on the resected tumour sample which correlates with the tumour volume. It is determined histologically (the depth in mm from the most superficial cellular layer of the skin to the deepest part of the tumour). When this is less than 1.5 mm then the 5 year survival is 92%, but the five-year survival falls to only 36% for a Breslow thickness greater than 3.5 mm.
It is desirable therefore that both General Practitioners and the general population should be aware what an early melanoma looks like and that it is important that such tumours should be seen early by medical personnel.
Most melanomas (55% approximately in white European populations) are superficial spreading melanomas which commonly arise from moles (probably around 60 to 70%). These lesions have a relatively slow growth rate and have frequently been developing for many months if not years by the time they present to the doctor. There is therefore at any one time a significant percentage of the general population with such lesions who would benefit from health education directed at early detection. Superficial spreading melanomas are usually larger in diameter than most moles (greater than 5 mm), with an irregular edge and variable colour. In order to facilitate the recognition of such lesions the general public should be advised to see their doctor if a mole changes in shape, colour or size.
The less common nodular melanomas have a much more rapid growth rate and may have the appearance of a red or pigmented lump which can bleed. It is much more difficult to give readily understandable advice about such lesions to the public which would enable them to distinguish between benign and malignant. The advice to see a doctor if they notice a new lump especially if it is pigmented or bleeding seems appropriate but of little help in distinguishing e.g. Campbell de Morgan spots (Cherry angiomas or angiokeratomas) from melanomas.
Britton JP, Dowell AC, Whelan P, Harris CM, A community study of bladder cancer screening by the detection of occult urinary bleeding. J Uro, 1992; 148 (3): 788-90.
Dent OF, Goulston KJ, Tennant CC et al., Rectal bleeding. Patient delay in presentation, Dis Colon Rectum, 1990; 33: 851-57.
Doherty V, and Mackie R, Reasons for Poor Prognosis in British Patients with Cutaneous Malignant Melanoma, BMJ, 1986; 292:987-9.
Fijten GH, Muris JW, Starmans R, Knottnerus JA, et al., The incidence and outcome of rectal bleeding in general practice, Fam Practice, 1993; 10 (3): 283-7.
Hennrikus D, Girgis A, Redman S, Sanson-Fisher R, A Community Study of Delay in Presenting with Signs of Melanoma to Medical Practitioners, Arch Dermatol, 1991; 127: 356-361.
Marks R and Hill D, Melanoma control: prevention and early detection. Pub. Union International Contre le Cancer, 1992 ISBN 0947283234.
In many developing countries, the uterine cervix is one of the most prevalent sites for cancer, comprising about 25% of all female cancers. In industrialised populations, the disease is less common. In eastern and central European populations, the annual age-adjusted (using the World Standard Population as referent) incidence rates for invasive disease are 15-25 per 100.000 women. In the Nordic countries, the annual incidence was 15-30 per 100.000 women before the start of large-scale mass screening programmes.
The effectiveness of screening for cervical cancer has never been demonstrated in a randomised preventive trial. There is, however, a great deal of non-experimental evidence, in terms of reduced incidence of invasive disease. Screening for cervical cancer reduces the incidence of invasive disease and is applicable as public health policy, but a wide variation is seen, from highly effective programmes to relatively poor ones.
The effectiveness of screening for cervical cancer has been evaluated on the basis of several non-experimental studies - case-control and cohort studies and of time trends and geographical differences. The largest of these is the collaborative study co-ordinated by the International Agency for Research on Cancer which showed that eradication of the disease is an unrealistic goal and that maximal protection after a negative smear is about 90%, which remains roughly the same during several years after the test. This conclusion is in agreement with the results of studies on the natural history of the disease, which have shown that most pre-invasive lesions progress to frankly invasive cancer only over several years.
The effects are somewhat smaller at a population level. In some of the Nordic countries, the reduction was about 80% in women in the age groups exposed most intensively to screening. In the mid-1980s, after several years of organised screening, the overall incidence was 5-15 per 100.000 woman-years. Because the incidence was decreasing before the screening programmes were begun, the trends probably indicate a minimal effect of the Nordic programmes.
An organised programme consists of several essential elements, including high attendance rates, quality control of the cervical smears and referral of confirmed cases for adequate treatment. These elements allow quality control, monitoring of the process and evaluation of outcome. Experience from the Nordic countries shows that such programmes are effective and consume less resources than programmes based on spontaneous participation.
High attendance is a prerequisite for effective screening. If the population to be screened is defined and the women within it are identified, personal invitations can be sent. Personal invitation is probably the single most important means of attaining high attendance, especially when it is combined with effective information through the mass media. Free service has also been shown to improve attendance. Quality assurance of all steps of the process, monitoring and constant evaluation of the proportion of cancer detected, false positives and false negative readings, are mandatory.
In conclusion, near maximal effectiveness is achieved by an organised programme with high coverage, in which screening is initiated at the age of 25 and is repeated at three- or five-yearly intervals to the age of 60. Extension of this approach should be considered only if maximal coverage has been attained, the resources are available and the marginal cost-effectiveness of the recommended changes has been evaluated.
IARC Working Group on Cervical Cancer Screening, Summary chapter. pp.133-142. In: Hakama M, Miller AB, Day NE, eds. 'Screening for Cancer of the Uterine Cervix', IARC Scientific Publications No. 76, IARC, Lyon (1986)
European Guidelines for Cervix Cancer Screening, Eur J Cancer 29 (supplement 4) (1993)
Hakama M, Magnus K, Petterson F, Storm H and Tulinius H, Effect of the organized screening in the Nordic countries on the risk of cervical cancer, pp 153-162. In: Miller AB, Chamberlain J, Day NE, Hakama M, Prorok P, eds. 'Cancer Screening', Cambridge: Cambridge University Press, 1991:
Wilson J and Jungner G, Principles and Practice of Screening for Disease (WHO Public Health Paper 34), Geneva, World Health Organization (1968)
Primary prevention of breast cancer through reduction of exposure to risk factors is not feasible at present; known risk factors are associated with small relative risks (generally less than 2) and are frequently not amenable to modification.
The role of diet is at present not well understood and further research is required; no specific dietary advice is available. Chemoprevention, by the use of dietary supplementation or tamoxifen, is being evaluated in large randomised trials in several countries. Until results from these trials are available no recommendations can be made for application to the general population.
To reduce the burden of breast cancer mortality in the European Union attention must therefore be focused on secondary prevention through early detection. The general aim of early detection is to identify breast cancers when they are smaller and at an earlier stage and with other favourable prognostic characteristics.
There are several strands of evidence indicating that this will reduce breast cancer mortality. Long-term studies of survival show a strong association between poor survival and increasing size and stage of the primary tumour. Trials of breast cancer screening have shown that cumulative rates of "stage II+" cancers in both the screened and the unscreened arms of the trials are highly predictive of subsequent breast cancer mortality. Stage II+ as defined by Tabar includes small node positive tumours and it is clear that detection should aim to be sufficiently early to avoid node positivity even in small tumours.
Further indirect evidence of the importance of early presentation comes from comparison of international patterns of incidence and mortality rates; there is poor correlation between these. Mortality rates are rising in many countries including most of the European Union, but they are falling by birth cohort in the United States, Canada, Australia, the United Kingdom, Switzerland and the Nordic countries. The falls can be attributed in part to population changes in known risk factors and, in particular, ages at which families are begun. It is considered that increased breast awareness and screening are responsible for much of the reduction.
There is now good evidence available from randomised trials conducted in the United States of America, Sweden, and Scotland, and involving over 250,000 women, that regular mammographic screening examinations of women aged between 50 and around 70 years will reduce their breast cancer mortality. The best estimates are that the size of the reduction may be around 30% if take-up of screening in the population is good and quality control standards high.
An overview of the Swedish trials reported relative risks of death of 0.71 in the group randomised to an offer of screening with 95% confidence internal 0.57-0.89 for women aged 50-59 at entry. Results for women aged 60-69 were almost identical. There is, as yet no clear evidence that screening benefits older women and it is certain that they are less willing to attend for screening.
More importantly, results for younger women (less than 50) are ambiguous with no trials having large enough statistical power to analyse these women separately. There are no statistically significant results for this age group reported but point estimates include both reductions and increase in breast cancer mortality in women offered mammographic screening whilst aged under 50 years.
Unfortunately, organised programmes of mammographic screening are not available at the present time to women in all countries of the European Union although pilot studies have now been established in all Member States without an organised National Mammographic Screening Programme.
At present, the use of mammographic screening for pre-menopausal women remains a topic for research rather than for routine health care. Yet 41% of the years of life lost due to breast cancer diagnosed before the age of 80 years are attributable to cases presenting symptomatically at ages 35-49 years. This underlines the necessity to conduct the necessary research on this issue.
Breast self-examination (BSE) is a simple method of early detection which is available for all women. It has however, been formally evaluated in a single United Kingdom study and the results were disappointing. Breast cancer mortality was reduced in only one of two English centres where teaching of BSE was introduced; differences in routine management have been proposed as an explanation of these differences.
In addition, breast examination practices among the women concerned may not have been enormously influenced by the education they were offered. In the absence of better alternatives, individual breast awareness and breast self-examination should be recommended to European women only when organised mammographic screening programmes are unavailable and, when relevant, between routine mammographic screens.
If this advice is followed, breast cancer incidence will not be reduced and, indeed, is likely to increase. The primary effect will be a reduction in mortality. Subsidiary benefits will include reduction in the absolute incidence (as well as merely the proportional incidence) of larger and higher stage disease, and increased use of lumpectomy and other less mutilating therapies.
Alexander FE, Anderson TJ, Brown HK et al., The Edinburgh randomised Trial of Breast Cancer Screening: results after 10 years of follow-up, Brit J Canc, 1994; 70: 542-48
Ellman R, Moss SM, Coleman D, Chamberlain J, Breast self-examination programs in the Trial of Early Detection of Breast Cancer, Brit J Canc, 1993; 68: 208-12.
Fletcher SW, Black W, Harris R, Rimer BK, Shapiro S, Report on the International Workshop on screening for breast cancer, NCI, 1993.
Nystrom L, Rutquist LE, Wall S et al., Breast cancer screening with mammography: overview of Swedish randomised trials, Lancet, 1993; 341: 973-979.
Tabar L, Gad A, Holmberg LH et al., Reduction in mortality from breast cancer after mass screening with mammography, Lancet, 1985; i: 829-832.
Wald NJ, Chamberlain J, Hackshaw A, Anderson T, Boyle P, Forrest P, Frischbier HJ, Hakama M, Rutqvist LE, Schaffer P, Seradour B, Tabar L, Rosselli Del Turco M and Van der Schueren E, Report of the European Society of Mastology (EUSOMA) Breast Cancer Screening Evaluation Committee (1993), The Breast 2:209-216 (1993)
Tubiana M, Holland R, Kopans DB, Kurtz JM, Petit JY, Rilke F, Sacchini V and Tornberg S, Commission of the European Communities "Europe Against Cancer" Programme. European School of Oncology Advisory Report. Management of Non-palpable and Small Lesions Found in Mass Breast Screening, Eur.J.Cancer 30:538-547 (1994)
The committee discussed a number of other issues in Cancer Epidemiology and Cancer Control and decided that the situation was not so clear that any recommendation could be made with a convincing probability of success in reducing cancer risk. It was felt that Screening for Prostate Cancer and Screening for Colorectal Cancer with Sigmoidoscopy required to be evaluated in randomised trials before any recommendations could be made to the general public.
At the present time, it is not yet clear whether participation in programmes of either screening for prostate cancer (using any combination of Digital Rectal Examination, Prostate Specific Antigen or Trans Rectal Ultrasound) or colorectal cancer (using either haemocult or sigmoidoscopy) would lead to a reduced risk of death from the disease among participants.
Screening for Oral Cancer was also considered and it was concluded that there was a great deal of further evaluation to be done, including randomised trials, before any conclusion of its efficacy could be made and recommendations considered. It was also recognised that more research work was necessary in breast cancer, particularly with regard to the efficacy of mammographic screening among women under the age of 50.
A number of cancer risk factors were considered and it was felt that more information was required regarding the magnitude and nature of a number of putative associations, including those between domestic radon levels and lung cancer risk, elecro-magnetic fields and childhood cancer risk, salt intake and gastric cancer risk and the possible protective effect of dietary vitamin supplementation and cancer risk, before any recommendations could be made to the General Public.
There are key references proposed for more detailed information and background regarding the points presented above in outlining the rationale behind the recommendations made for the revised European Code Against Cancer. These are presented separately with each of the points described above.
European Institute of Oncology
Via Ripamonti 435
Tél.: 39/2 57305416
Télécopieur: 39/2 57307143
Centre Antoine Beclere
Faculté de Médecine
45, rue des Saints-Pères
Tél.: 33/1 42862295
Télécopie: 33/1 47039385
Division of Epidemiology and Biostatistics
European Institute of Oncology
Via Ripamonti 435
Tél.: 39/2 57489816
Télécopie: 39/2 57489813
F E Alexander
Department of Public Health Sciences
University of Edinburgh
Edinburgh EH8 9AG
Scotland, United Kingdom
Tél.: 44/31 6506984
Télécopie: 44/31 6676129
F. Calais da Silva
IV Curso Portugues de Oncologia Urologica
Av. Oscar Monteiro Torres 8 - 4 Esq.
Tél.: 351/1 7952494/5
Télécopie: 351/1 7952497
L J. Denis
Algemeen Ziekenhuis Middelheim
Tél.: 32/3 2803602
Télécopie: 32/3 2184696
Escuela Nacional de Sanidad
Ministerio de Sanidad y Consumo
Calle Sinesio Delgado 10
28029 MADRID (Spain)
Tél.: 34/1 3148398
Télécopie: 34/1 3150200
University of Tampere
Department of Public Health
Tél.: 358/31 2156788
Télécopie: 358/31 2156057
Service de Pneumologie
1, Av. Claude Vellefaux
75475 Paris Cedex 10
Tél.: 33/1 42499618
Télécopie: 33/1 42499395
Rijksinstuut Voor Volksgezondheid en Milieuhygiene
9, Antoinie Van Leeuwenhoeklaan
3720 BA Bilthoven
Tél.: 31/30 749111
Télécopie: 31/30 291516
C. La Vecchia
Istituto di Ricerca Farmacologica Mario Negri
University of Milan
Via Eritrea, 62
Tél.: 39/2 39014518
Télécopie: 39/2 33200231
Centro Nacional de Epidemiologia
Sinesio Delgado, 6
Tél.: +34 1 3145530
Télécopie: + 34 1 3147970
Department of Dermatology
The Royal London Hospital
London E1 1BB
Tél.: 44/71 2477503
Télécopie: 44/71 3779213
School of Dentistry
Health Science Faculty
University of Copenhagen
Norre Alle 20
Tél.: 45/35 326700
Télécopie: 45/ 35 326505
International Agency for Reseach on Cancer
150 Cours Albert Thomas
69372 LYON Cedex 08
Tél.: 33/ 72738408
Télécopie: 33/ 72738564
Eastman Dental Institute for Oral and Dental Healthcare Sciences
University of London
256 Gray's Inn Road
London WC1X 8LD
Tél.: 44/71 9151172
Télécopie: 44/71 9151105
Provinciaal Instituut voor Hygiene
2000 ANTWERPEN 1
Tél.: 32/3 2385884
Télécopie: 32/3 2377022
Danish Cancer Society
Division of Cancer Epidemiology
Department of Cancer Registration
P.O. Box 839
Tél.: 45/35 268866
Télécopie: 45/35 260090
Programme "Europe contre le Cancer"
Bat. J. Monnet
Plateau du Kirchberg
Télécopie: 352/ 430134511
Programme "Europe contre le Cancer"
200, rue de la Loi
Tél.: 32/2 2951742
Télécopie: 32/2 2962393
Director, Medical Research Council
Clinical Oncology and Radiotherapeutics Unit
Cambridge CB2 2QQ
Tél.: 44/223 245133
Télécopie: 44/223 412213
Centre Hospitalier de Luxembourg
4, rue Barble,
Tél.: 352 44112084
Télécopie: 352 458762
Chair of Oncology and Radiotherapy
Faculty of Medicine
Vrazov trg No.2