Current Strategies for Cancer Prevention : Chemoprevention

Observations at ecological level show strong correlation between exogenous exposures, such as fat consumption, and risk of cancers. The correlations are less but significant at an individual level between many dietary items and cancer risk based on case-control and cohort studies. Most specific attempts to evaluate the role of diet on cancer risk stems from use of serum sample banks and estimation of different components of biochemistry in cases of cancer and healthy controls. The extension of this vast amount of epidemiological knowledge has resulted in preventive trials, chemoprevention of cancer, and in routine use of preventive substances, vitamins and minerals. However, the trials are relatively few and even less frequent are those with invasive cancer as end point. Furthermore, the results of these trials have been rather negative, and it seems at present that vitamins and minerals videly used in adult age for chemopreventive purposes are relative ineffective to prevent occurrence of invasive cancer or death from cancer. This does not imply that these chemical substances were not causes of cancer. J Epidemiol,1996 ; 6 : S39-S42.

The basis for primary prevention of cancer is well established, because important causes of cancer are known. However, apart from reducing cigarette smoking, few easily applicable measures to decrease cancer incidence are available.
Smoking has been estimated to cause about one third of cancer deaths in western countries u.
Approaches to the prevention of cancer vary. Traditionally, the most common method has been health education on an individual or community basis via the mass media or by other channels. In several countries, other means have also been applied: legislative action (such as banning of advertisement), price regulation and policy decisions in relation to health services. A reduction in tobacco use has been the principal objective in most such actions. Other environmental changes have been attempted, for example, in the development of dietary policies and advice, the elimination or reduction of exposure to chemical carcinogens from the working and general environment, and the improvement of radiation protection.
Recently there is much interest in chemoprevention in can- Optimal in many ways to show the role of environmental exposures in the etiology of cancer is through use of biological sample banks collected in the past and linkage of the sample bank and a cancer registry. One of the largest studies was run in Finland, a bank of 40,000 serum samples established in late 1960's by the Social Insurance Institution was linked with the Finnish Cancer Registry early 1980's. More than 700 cancers with 1400 controls were analysed for several vitamins, trace elements, infections and tumour markers. Table 1 shows the risk of cancers among those with low levels (lowest quintile except three lowest quintiles for alpha-tocopherol for males) of retinol, beta-carotene, alpha-tocopherol and selenium. The relative risks for stomach cancer were high but also for breast and lung cancer there were associations with most of the biochemical substances studied. The risk of total cancer increased with the number of the substances with low level. The estimates for population etiologic fractions for dietary factors were close to the estimate of one third by Doll and Peto 1).
Worldwide there is a large consumption of chemopreventive agents, mainly vitamins and minerals. The scientific evidence on their effectiveness is limited, however. International Union against Cancer and several other international bodies have shown interest in chemoprevention in cancer control. The following is mainly based on the reviews of UICC, WHO and EU 23) . Much of the problems in evaluation of cancer prevention in general4) apply also to chemoprevention.
Buiatti et al 3). combined the information available on both published and on-going chemopreventive trials, which they were able to identify altogether 83 which were substantially more numerous than trials on diet (8 in number). Colon, lung , oral cavity and skin were the primary sites most often subjected to chemopreventive interventions. The agents commonly used in the intervention were beta-carotene, synthetic retinoids, calcium or several vitamins combined. Calcium was the agent for studies to reduce the risk of colon cancer or oesophageal cancer whereas the target primary sites were more wide spread in the vitamin trials.  1968-1977 (14).
Reduction in the occurrence of invasive primary cancers is the most convincing evidence on the effectiveness of prevention. Relatively few of the chemopreventive trials have the invasive disease as an end point. Typically, the large trials on lung, oesophageal and breast cancer have incidence of or mortality from invasive cancer as an outcome. Early markers of DNA damage, cell proliferation, mutagenicity etc. are common outcomes as well as occurrence or recurrence of precancerous lesions.
The first results of the large intervention studies were published from the alpha-tocopherol, beta-carotene lung cancer intervention trial (ATBC study) carried out in Finland by the National Public Health Institute 5. 6). About 29000 male smokers were randomized into both alpha-tocopherol and betacarotene, alpha-tocopherol only, beta-carotene only and placebo only arms. There was no protective effect of alpha-tocopherol nor beta-carotene on lung cancer or total cancer ( Table  2). In fact, the numbers of new cases and deaths from cancer were somewhat larger in the beta-carotene group than in the placebo group. Essentially similar results were derived from large U.S. studies 7.8).
The only positive result of chemoprevention to reduce risk of invasive cancer is the reduced incidence of contralateral breast cancer among breast cancer patients with tamoxifen treatment 9). There is going on international breast cancer intervention study to find out the applicability of those results in healthy population and to quantitate the risks of the intervention.
Cost-effectiveness of chemoprevention is considered infrequently. Habbema et ally) showed that only few life weeks would be gained per woman in average assuming a successful chemoprevention against colon cancer starting at middle age . The preventive treatment may be of duration of several decennia. Therefore, from several hundreds to more than one thousand years of chemopreventive treatment is needed to gain one life year. If the activity of chemoprevention itself or harmful effects of it will cause a marginally small decrease in quality of life, there will be a net loss instead of gain in the quality adjusted length of life.
Chemoprevention based on vitamins and minerals has not been shown to be effective so far . This does not imply that  2 show the very recent trends of both incidence and mortality for cancer of digestive organs. It was assumed that focusing on the recent trends in incidence also recent trends in causes could be established. The trends in incidence of and mortality from total digestive cancer were decreasing in most age groups from 30 to 69 years. The changes were small but mainly according to the expectation, i.e. more substantial among the young, among women and in the last period (Figures 1 and 2). In summary, it seems that research based on specific preventive trials has been rather negative as to indicate the potentials of prevention whereas more robust methods at ecological level give a more positive answer as to the effectiveness of primary prevention in cancer control. However, little is known about the causes of changes in environment and life-styles at the population or individual level. Such changes may be due educational and regulatory efforts of health authorities and to growing health-consciousness among individuals. They may also be unrelated to deliberate health-based decisions, as when food fashions change or when purely commercial factors lead to the appearance or disappearance of certain products from the market.