Int. J Cancer: 43, 967-969 (1989)
UICC WORKSHOP ON EVALUATING INTERVENTIONS TO REDUCE CANCER RISK
Meeting held at Reykjavik, Iceland, September 21-24, 1988
Matti HAKAMA1, Valerie BERAL, Joseph CULLEN, and Max PARKIN
A UICC Workshop on evaluation of primary preventative
interventions against cancer was held in Reyjavik, Iceland, on
September 21-24, 1988. This report summarizes the topics covered
and conclusions reached.
Since some major causes of cancer are known, the theoretical
basis for the primary prevention of cancer is established. However,
practicable ways of avoiding the onset of cancer are largely
limited to reducing smoking cigarettes. smoking has been estimated
to cause about one-third of all cancer deaths (Doll and Peto, 1981)
and a similar proportion of male cancer cases (Higginson and Muir,
1979;Wynder and Gori, 1977) in Western countries.
Approaches to the prevention of cancer vary. Traditionally the
most common method has been health education on an individual
community basis via the mass media or otherwise. In several
countries other means have also been applied: legislative action -
e.g. banning advertisements - price policy, and policy decisions
in relation to health services. A reduction in tobacco use has been
the principle objective in such actions. Other environmental
changes have also been attempted, for example the development of
dietary policies and counselling, the elimination or reduction of
chemical carcinogens in the working environment, and enhancements
in radiation protection. Physical exercise and chemoprevention have
been suggested as a means of reducing the adverse effects of
unhealthy lifestyles.
Preventative efforts are mainly evaluated in terms of follow
up and monitoring for changes in causative exposures-risk factors
of cancer. Much less is known about the relationship between the
preventive intervention and the final outcome, i.e., occurrence of
cancer or otherwise. Efforts to evaluate the effectiveness of
primary preventative measures are hampered by the paucity of
reliable data and of well-established analytical methods.
However, the effectiveness of primary preventative measures
has been demonstrated in several circumstances. Sometimes a
carcinogenic hazard has been removed from the environment, and the
effectiveness of this action can be evaluated from the study of
subsequent incidence or mortality rates, with no attempt to involve
a control group. Specific examples are in industry, where removal
of hazards has resulted in the virtual elimination of some
occupational cancers. Clinical treatment or diagnostic practices
have sometimes had carcinogenic side effects; when these practices
were changed after recognition, rates of cancer at the population
level showed a substantial decrease. In interventions such as
these, however, the exact design and method of intervention is
rarely known.
Time trends and geographical differences in cancer rates
indicate substantial changes and differences in the risk factors.
Studies of time trends in cancer in relation to time trends in
exposure to risk factors-particularly tobacco smoking and alcohol
consumption- are the most illuminating. International trends in
lung cancer mortality, in particular, can be convincingly related
to cohort-specific trends in smoking, particularly if allowance is
made for the introduction of low-tar and filter cigarettes in the
last 30 years. Studies of migrant populations are a well
established method of demonstrating the effect which environmental
change can play in the risk of cancer; however, the extent to which
the change in cancer risk in migrants can be related to changes in
their external or socio-cultural environment has been poorly
investigated.
Epidemiological studies of individuals who have adopted
potentially healthier habits or lifestyles are relatively few, and,
for practical purposes, are confined to the investigation of cancer
in ex-smokers. Such studies show a marked decline in risk, which
is proportional in time since quitting, and they constitute the
most powerful evidence for the effectiveness of stopping smoking
in preventing cancer.
Little is known, however, about the causes of changes in
environment and life-styles at the population or individual level.
Such changes may be due to efforts of health authorities or due to
health conscious changes in the behaviour of individuals. From the
health related point of view they may depict a more or less
spontaneous, i.e., not health-conscious decrease in the prevalence
and intensity of exposures in the environment and in the behaviour,
just as the appearance of such exposures was independent of health
related actions.
The main purpose of the workshop was to accumulate results on
preventative interventions. relatively few studies have been
performed in which specific, documented preventative interventions
can be evaluated with respect to their effort on cancer risk. Those
available are reviewed in this paper. Most such studies involved
preventative programmes against cardiovascular diseases. Because
of this background, the studies reviewed were mainly aimed at
reduction in smoking and changes in diet, the most important causes
of cancer known at present.
WHO European Collaborative Trial in the Multifactorial Prevention
of Coronary Heart Disease
The study was based on group randomization of 80 factories in
several european countries employing 63,732 men. Measures adopted
were education on diet, smoking and physical exercise, and
supplying of appropriate menus at workplace canteens. The change
in the combined risk factor score ranged from 0.4 to 28.2% in
different countries. Results on cancer mortality after 6 years of
follow-up were available from the UK, Poland, Italy and Spain.
O)nly in Spain was the total cancer mortality rate lower in the
intervention group than in the controls (RR = 0.5, p = 0.02) in
spite of the fact that total mortality and incidence of CHD were
smaller in the intervention than in the control group.
The US Multiple Risk Factor Intervention Trial (MRFIT)
More than 12,000 men were individually randomized to either
an active intervention or usual care control group. The
intervention consisted of individual and group sessions to persuade
cigarette smokers to give up smoking, give dietary advice to
achieve lower blood cholesterol levels, and the use of anti-
hypertensive medication to control high blood pressure. data on
mortality over 10.5 years of follow-up is available. The clinical
trial data on the impact of multiple preventions, especially
stopping smoking and dietary changes, on cancer mortality showed
no significant differences but the material was too limited to
allow firm conclusions to be drawn.
The Finland North Karelia Study
This study is a non-randomized community trial. The
intervention in smoking and diet was achieved by health education
of the public, by reorganizing the community and health services
and by changing the environment. A 14-year follow-up for cancer
after the start of the programme was carried through the Finnish
Cancer Registry and comparisons were made of cancer morbidity among
the North Karelian population, in the population adjacent to North
Karelia and in the rest of Finland. Lung cancer among males was
about 10% less common than expected, as was breast cancer among
women. The number of cancers of the stomach and oesophagus was
somewhat greater than expected. The incidence of other cancers
related a priori to smoking and diet was approximately as expected.
The Indian Oral Precancer Study
This was a cohort study with non-concurrent controls based on
some 18,000 individuals, 12,000 of whom were subjected to health
education against tobacco use. Over a period of at least 8 years,
substantial differences in the use of tobacco persisted in favour
of the intervention group. the incidence rate of leucoplakia was
much lower in the intervention group (RR = 0.4) but no differences
have so far emerged between the observed and expected number of
oral cancer.
Other Published Studies
In the UK Whitehall study (Rose et al., 1982) about 1500 men were
individually randomized; the intervention group was subjected to
anti-smoking advice. After one year of follow-up, in the
intervention group consumption of cigarettes was one quarter of the
level among controls. The difference persisted up to ten years but
at a lower level. According to the results published in 1982 (Rose
et al.) no differences were observed in the total number of cancer
deaths. There were fewer cases of lung cancer in the intervention
(18) than in the control (24) group, but non-lung cancer deaths
were higher (28 vs. 12) in the same group. This unexpected finding
was attributed to chance by the authors.
Several other intervention studies mainly aiming at lowering
cholesterol dietary levels or reducing smoking failed to show any
consistent pattern (Ederer et al.,1971; Hjermann et al., 1981;
Pearce and Dayton, 1971) Most of such studies reported only a few
cases of cancer.
The studies, Collaborative WHO, MRFIT,Finnish North Karelia
and Indian Oral Precancer, reviewed more carefully in the workshop,
were based on about 1800 cancers during a follow-up ranging from
6-14 years. All these studies have demonstrated a substantial to
moderate change in intensity and prevalence of risk factors-smoking
and some dietary practices-in the target populations indicating the
success of such intervention programmes in achieving changes in
behaviour. Smoking and inappropriate diet are likely to be the most
important causes of total cancer, since up to two-thirds of all
cancer deaths were attributed to these risks by Doll and Peto
(1981). It might therefore be expected that changes in cancer risk
would follow an intervention which was successful on the basis of
process indicators. However, the efficacy of the preventative
trials in reducing the risk of cancer seem s to be low. Several
explanations from the negative results should be taken into
consideration, however, before such a conclusion is drawn.
None of the studies referred to was designed to study the
prevention of cancer. Nevertheless, it is not certain that the
interventions would have been very different if this had been the
case. Smoking is a risk factor for several cancers and because of
the high attributable risk for lung cancer, the smoking-related
interventions should have led to a reduction of lung cancer risk
if they were effective. Less is known about the dietary factors
affecting cancer risk, although, for cancer, the elements of diet
suspected of producing an increased risk are similar to those for
cardiovascular diseases. Only for cancer of the upper
gastrointestinal tract may risk be elevated by attempts to reduce
fat and sugar consumption and to lower the general intake of
calories.Some of the trials were designed to promote a diet high
in polyunsaturated fat and low in saturated fat and cholesterol.
Relatively little is known of the effects of such dietary changes
on the risk of cancer.
Because the main focus of the studies was on the prevention
of cardiovascular diseases, the accuracy of follow-up and recording
of incident cases of cancer or cancer deaths was not necessarily
of the same quality as for the cardiovascular events. For the
community trial, however, the cancers were identified by a nation-
wide, population-based registration system of high reliability.
Furthermore, even if less accurate, the comparability of the cancer
death certificates is probably valid between the cases and
controls, and cancer diagnoses may be even less biassed(But more
affected by random errors) than the diagnoses for cardiovascular
deaths. It is therefore unlikely that poor quality of cancer
diagnosis accounts for the limited effect.
Cancers are a group of diseases with long latent period
between first exposure and diagnosis. When the risk factor in
question acts late in the carcinogenic process, reduction of
exposure might be expected to have a relatively rapid effect. For
example,risk of lung cancer declines quite rapidly towards levels
found in non-smokers within 15 years of stopping smoking (Doll and
Peto, 1981). Migrant studies suggest that colorectal cancer risk
also changes relatively rapidly after a change in the environment
(Haenzel, 1970). The risk may therefore have declined in the
intervention groups after the follow-up of 6-14 years available for
the intervention trials, but because evaluation is based on all
cases or deaths within the follow-up period, the results will be
greatly diluted by cases with short latent periods during the first
years of follow-up. Probably only the Finnish North Karelia study
had a long enough follow-up for small effects of intervention to
be detected, and from this study a total reduction of about 10% in
the risk of lung cancer emerged.
It should also be noted that health education in some studies
was of relatively short duration and of low intensity. Furthermore,
most of them were undertaken in countries where health
consciousness tends to spread relatively rapidly. It is likely that
in the long run the control populations would also be exposed to
similar information as offered in the health education
interventions for the experimental group, and sometimes to similar
services. In fact, the Indian study showed a substantial and long
lasting effect of a fairly limited health education campaign.
Dilution of the information in the control group imply that such
information is neither effective nor necessary. In recent years,
several community-based programmes have been started-again
primarily aimed at cardiovascular disease-with continuous efforts
to reduce smoking and change dietary habits by a variety of
strategies. Unfortunately, no data are yet available on risk of
cancer or on other diseases. The potential for evaluation of such
programmes, in terms of reduction or cancer incidence and other
outcome indicators, should not be neglected. Although the study
design may be a poor one for inferring cause and effect, existing
data collection systems, particularly cancer registries can be used
at little extra cost.
The designs and populations were variable and one should not
expect an identical effect in all studies. the studies were in
principle similar: an intervention-admittedly from simple to
sophisticated-was made for health purposes. A substantial to
moderate effect was obtained in the risk factor which the
intervention aimed at changing. However, it seems valid to conclude
that the effects on cancer risk of interventions mainly based on
health education on smoking and diet have not so far resulted in
any substantial effect on cancer risk. This does not imply that
such efforts were ineffective. The exposure and follow-up have been
relatively short and similar changes in behaviour may have been
diluted in the control groups.
ACKNOWLEDGEMENTS
We gratefully acknowledge the financial and other support of
the Icelandic Cancer Society, the International Agency for Research
on Cancer, the National Cancer Institute and the Nordic Cancer
Union.
REFERENCES
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men on cholesterol lowering diets, Lancet, II, 203-206 (1971).
HAENSZEL, W., Studies of migrant populations. J. chron. Dis.,
23, 289-291 (1970).
HIGGINSON,J. and MUIR, C.S., Environmental carcinogenesis:
misconceptions and limitations to cancer control. J. Nat.
Cancer Inst., 63, 1291-1298 (1979).
HJERMANN, I., HOLME,I., VELVE BYRE, K. and LEREN, P., Effect of
diet and smoking intervention in the incidence of coronary
heart disease: report from the Oslo study group of a
randomized trial in healthy men. Lancet, II, 1303-1310 (1981).
PEARCE, M. and DAYTON, S., Incidence of cancer in men on a diet
high in polyunsaturated fat. Lancet, I, 464-467 (1971)
ROSE, G., HAMILTON, P., COLWELL, L. and SHIPLEY, M., A randomised
controlled trial of anti-smoking advice: 10 year results. J.
Epidem. Comm. Hlth, 36, 102-108 (1982).
WYNDER, E.L. and GORI, G.B., Contribution of the environment to
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LIST OF PARTICIPANTS
ARNESEN, E. ISM, P.B. 417, N-9001 Tromso, Norway.
BERAL, V., The Radcliffe Infirmary, Oxford 0X2 6HE, UK.
BURING, J., Brigham and Women's Hospital, Harvard Medical School,
55 Pond Ave, Brookline, MA 02146, USA.
BYAR, D., Division of Cancer Prevention and Control, National
Cancer Institute, Bethesda, MD 20892-4200 USA
CARLETON, R., Pawtucket Heart Health Program, memorial Hospital,
126 Prospect Street, Pawtucket, RI 02865, USA.
CHENEY, J., International Agency for Research on Cancer, 150, Cours
Albert-Thomas, 69372, Lyon Cedex 08, France.
COLEMAN, M., International Agency for Research on Cancer, 150,
Cours Albert-Thomas, 69372, Lyon Cedex 08, France.
CULLEN, J., Division of Cancer Prevention and Control, National
Cancer Institute, Bethesda, MD 20892-3100, USA.
DOBROSSY, L., Cancer unit, World Health Organization, Regional
Office for Europe,8, Scherfigsvej, DK-2100 Copenhagen O/,
Denmark.
FRIEDEWALD,W., Disease Prevention, National Institutes of Health,
Bethesda, MD 20892, USA.
GUPTA, P., Tata Institute of Fundamental Research, National Centre
of the Government of India for Nuclear Science and
Mathematics, Home Bhabha Road, Bombay 400 005, India.
HAKAMA, M., University of Tampere, Department of Public Health, Box
607, SF-33101 Tampere, Finland.
HAKULINEN, T., Finnish Cancer Registry, LIISANKATU 21, SF-00170
Helsinki, Finland.
KALDOR, J., International Agency for Research on Cancer, 150, Cours
Albert-Thomas,69372, Lyon Cedex 08, France.
LAMM, G., Klinikum der Universitat Heidelberg, Abteilung Klinische
Soczialmedizin, Bergheimer Strasse 58, D-6900 Heidleberg 7,
FRG
LAW, M., The Medical College of St. Bartholomew's Hospital,
University of London, Charterhouse Square, London ECIM 6BQ,
UK.
LOPEZ, A., Globel Epidemiological Surveillance and Health Situation
Assessment, World Health Organization, 1211 Geneva 27,
Switzerland.
PARKIN, M., International Agency for Research on Cancer, 150, Cours
Albert-Thomas, 69372, Lyon Cedex 08, France.
SASAKI, R., Department of Preventative Medicine, School of
Medicine, Nagoya University, Tsurumai-cho, Showa-ku, Nagoya
466, Japan.
SWERDLOW, A., London School of Hygiene and Tropical Medicine,
Keppel Street, London WC1E 7HT, UK.
TULINIUS, H., Icelandic Cancer Society, PO Box 523, 121 Reykjavik,
Iceland.
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(1) To whom reprint requests should be sent.
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