Author:

Paolo Vineis

Introduction

The distribution of different types of tumours shows clear differences across the planet: whereas the most frequent in high-income countries are cancers of the breast, of the colon and of the lungs, low-income countries present higher incidence and mortality rates for cancers of the stomach, liver and cervix uteri, all of which are largely or fully (cervix uteri) of infectious origin. The rapid variability of cancer rates over the course of time and between geographical areas debunks a common prejudice that cancer is essentially a genetic disease. The misunderstanding lies in the fact that the acquired genetic damage (e.g. mutations) is confused with changes transmitted by inheritance. Tumours are unquestionably due to alterations acquired by the genetic material (DNA) but only to a small extent (from 5 to 10%) are they hereditary tumours. This means that genetic screening does not play a major part in cancer prevention, if not in a very limited way (counselling in high-risk families), and this chapter is essentially based on the primary prevention of carcinogenic exposures (environmental or behavioural).

Historically, an important piece of evidence of the fact that most tumours have an environmental or behavioural origin and therefore are preventable comes from the study of migrant populations: after a certain period of time those who migrate acquire the same risk of cancer and other diseases of the area where they have settled (Haenszel and Kurihara, 1968). The case of Japan is well known: in the 1970s, stomach cancer was very frequent whereas that of the colon was not, contrary to what was observed with North America; however, when the Japanese emigrated to the United States, their rates of cancer rapidly aligned with those of the local population, with an increase in tumours of the colon and a reduction in those of the stomach.

Since the history of cancer prevention is relatively recent, we start with the current recommendations, to consider then their history. We are not considering in this chapter secondary prevention, i.e. screening practices, that would require a separate treatment. The history of evidence-based cancer prevention is very recent, depending on the epidemiological discoveries. Therefore, we start from the period after WWII.

What is recommended today to prevent cancer

These are the current twelve recommendations of the European Code Against Cancer, that reflect less than one century of research:

1. Do not smoke. Do not use any form of tobacco.
2. Make your home smoke free. Support smoke-free policies in your workplace.
3. Take action to keep a healthy body weight.
4. Be physically active in everyday life. Limit the time you spend sitting.
5. Have a healthy diet: eat plenty of whole grains, vegetables and fruit; limit high-calorie foods (foods high in sugar or fat); avoid processed meat, limit red meat and foods high is salt.
6. If you drink alcohol of any type, limit your intake. Not drinking alcohol is better for cancer prevention.
7. Avoid too much sun, especially for children. Use sun protection. Do not use sunbeds.
8. In the workplace, protect yourself against cancer-causing substances by following health and safety instructions.
9. Find out if you are exposed to radiation from naturally high radon levels in your home. Take action to reduce high radon levels.
10. For women: Breastfeeding reduces the mother’s cancer risk. If you can, breastfeed your baby; Hormone replacement therapy (HRT) increases the risk of certain cancers. Limit use of HRT.
11. Ensure your children take part in vaccination programmes for: Hepatitis B (for newborns); Human papillomavirus (HPV) (for girls).
12. Take part in organized cancer screening programmes for: Bowel cancer (men and women); Breast cancer (women); Cervical cancer (women).

WHO reports on non-communicable diseases, like the 25 × 25 strategy of the United Nations, list amongst the main “behavioural” risk factors for cancer tobacco, alcohol, little physical activity and an imbalanced diet. However, cancer is a group of diseases that are far more heterogeneous than other non-communicable diseases and requires more structured and locally specific policies than those proposed by the WHO, which are focused on a small number of risk factors more relevant to the Western countries (Wild 2012). Even though access to effective treatment and the development of new therapies are fundamental components in the fight against cancer, they will never be completely effective in the absence of prevention (Bray et al. 2015). A strong argument in favour of prevention is that the causes can be removed permanently, i.e. the effort does not have to be renewed at each generation, as is the case for treatment. The role of prevention is particularly important where the resources are scarce, because it entails a substantial saving compared to the costs of diagnosis and therapies.

A historical journey

Tobacco

Ironically, Nazi Germany was the first to condemn tobacco use, funding research against it while levying taxes on tobacco products, and banning tobacco in various public places. In 1950, Sir Richard Doll published in the British Medical Journal research that showed a close link between smoking and lung cancer. The British Doctors study, a large prospective study, ensued in a few years. Similar investigations were conducted by the American Cancer Society (Cancer Prevention Study I and II, starting in 1959).

Tobacco is a powerful carcinogen with multiple effects and has a strong and growing impact on a planetary scale; it causes cancer of the lungs, of the upper respiratory tract, of the pancreas, of the stomach, of the liver, of the urinary tract, of the kidneys, of the cervix uteri and some forms of myeloid leukaemia. For some cancers (lung and upper respiratory tract), tobacco is the main cause, whilst for others it enters into a multifactorial mechanism together with other agents (like HPV for cervix uteri). Smoking is currently responsible for about 30% of all the tumours in developed countries and of a lower, but rapidly growing, percentage in low-income countries. It is also responsible for a higher number of early deaths from cardiovascular and respiratory diseases than from cancer.

Legislation against tobacco has been introduced very late, many years after the 1964 US Surgeon General Report on the effects of tobacco. The latter was strongly attacked by the tobacco industry. In fact in the United States, the Family Smoking Prevention and Tobacco Control Act (Tobacco Control Act) became law only in 2009. The fight against tobacco has been effective in some countries, to the point of making a substantial contribution to the decline of mortality. In the United States, between 1991 and 2024 the rates of mortality due to cancer decreased by 33%, and this was mainly due to decreasing prevalence of smoking, plus early diagnosis (https://www.cancer.gov/about-cancer/understanding/statistics).

Opposite trends, however, are observed in low and middle-income countries, where the absolute number of cases and the rates of incidence and mortality are increasing and are destined to further increase for many years to come, in part due to tobacco. The Framework Convention on Tobacco Control has been approved by the World Health Organization in 2003 (https://treaties.un.org/doc/source/RecentTexts/FCTC_en.pdf). Whilst the full implementation of the Framework Convention by the countries that have signed it is vital for successful prevention, unfortunately it has been hindered by the World Trade Organization in the name of free trade.

Occupational Carcinogens

The carcinogenicity of asbestos was discovered in 1940s, and that of aromatic amines in 1950s. From 1921, when the International Labour Office (ILO) introduced the first specific regulations, great progress has been made in the prevention of occupational tumours in the high-income countries. In these countries, the elimination or a substantial reduction of exposure to asbestos, aromatic amines, benzene, benzidine and other carcinogens has prevented tens of thousands of cases of cancer. For example, there is convincing evidence of the fact that a decline in bladder cancers and leukaemia amongst workers in the United States and Great Britain followed respectively to the banning of aromatic amines and benzene.

One of the most urgent problems to be faced is the fact that productions using carcinogenic substances tends to be exported to low-income countries.

Diet and Cancer

Obesity is an important risk factor for breast, colon, endometrial, kidney, oesophagus and pancreas cancer. Alcohol is clearly associated with cancer of the liver, of the upper respiratory tract, of the breast and of the colon. A diet poor in fibre has been related to tumours of the colon-rectum. However, despite the progress and a massive body of research done in the past decades, the comprehension of the relations between diet and tumours is still fairly uncertain, in particular as far as the mechanisms of action and the role of the individual nutrients are concerned.

Recommendations based on a systematic review of evidence have been published by the World Cancer Research Fund starting in 1997 (https://www.wcrf.org/preventing-cancer/cancer-prevention/our-cancer-prevention-recommendations) and suggest that regular physical activity; a reduced consumption of fats, sweetened drinks, alcohol and salty foods (salt is a risk factor for tumours of the stomach as well as the main cause of hypertension); a varied diet rich in fruit, vegetables and pulses; and keeping weight in the norm can prevent various forms of cancer.

Concerning diet, we have to mention the multiple randomized trials based on supplementations, including the 2009 results of the very large Selenium and Vitamin E Cancer Prevention Trial (SELECT) for prostate cancer. Overall, vitamin supplementation has not been found to be effective in preventing cancer. Instead, chemoprevention trials have shown that aspirin can reduce the risk of colorectal cancers.

Infectious Carcinogenic Agents

Human Papilloma Virus has been identified as the necessary cause of cervical cancer thanks to the research of the German virologist zur Hausen in the mid 1980s (for which he obtained the Nobel prize) (https://pmc.ncbi.nlm.nih.gov/articles/PMC10945753) and the epidemiological studies of, among others, Nubia Munoz (https://pubmed.ncbi.nlm.nih.gov/11091143). Helicobacter pylori, similarly, has been discovered as a major cause of stomach cancer (though not a necessary cause) by joint work of virologists in 1983, and epidemiologists later on. Helicobacter pylori, hepatitis B and C viruses and the papillomavirus (HPV) are responsible for an important percentage of tumours of the stomach, liver and cervix uteri, respectively.

One of the most important achievements in recent years in cancer research has been the development of an anti-HPV vaccine to prevent tumours of the cervix uteri. Ensuring that the vaccine is available to the poorest populations, who are those with the highest incidence of tumours of the cervix uteri, is decisive.

Another effective vaccine is that against hepatitis B, and in this case too, it is particularly important that it becomes available in poor countries where the frequency of infection is higher. A reduction in the incidence of liver cancer has already been observed in the countries that introduced the vaccine in the 1980s.

Environmental Carcinogens

The extent of exposure to environmental carcinogens in the world is unknown, in particular in low-income countries, although the total figure of tumours that can be attributed to them may number hundreds of thousands, just limiting the calculation to known carcinogens for which data on exposure are available (arsenic, atmospheric pollutants, aflatoxins, polychlorinated biphenyls—PCB, asbestos). The effects of additional exposures, such as to heavy metals (chromium, cadmium, nickel, beryllium) and to other carcinogens are difficult to quantify because we do not have adequate information on the spread and number of people exposed in low-income countries (Vineis and Xun 2009).

Strong evidence about the carcinogenicity of ambient air pollution has come in recent years with large epidemiological studies. Atmospheric pollution is one case where the quantitative and qualitative increase of research (in particular thanks to the ESCAPE multicentric study on the chronic health effects of pollution) has allowed dissipating uncertainties, showing that air pollution—due mainly to traffic—has numerous and important repercussions on health, in particular for cardiovascular diseases, for the respiratory system and for lung cancer (Raaschou-Nielsen et al. 2013).

The Future: Threats of Globalisation for the Primary Prevention of Cancer

In September 2011 at the “United Nations High-level Meeting on Noncommunicable Disease (NCD) Prevention and Control”, the world’s leaders committed themselves to energetically facing up to the threatening epidemic of degenerative chronic diseases. The main concerns include the great economic and social consequences of the epidemic. Eight months later, the Assembly of the WHO set the objective of reducing the mortality rates for NCD by 25% by 2025. Known as the 25 × 25 strategy, it has been incorporated into the WHO plan of action for 2013–2020, which in turn lists nine national objectives. Two objectives are general: to reduce mortality from NCD and halve the increase in obesity and diabetes. The other seven are specific: a reduction in the consumption of alcohol, salt in the diet and smoking, control arterial pressure, an increase in physical activity, greater access to pharmacological treatment of people at a high risk of cardiovascular diseases and a wider access to basic technologies and essential medicines. It is to be noted that at national level these objectives are “voluntary”, i.e. the States have to find the resources to implement them.

As can be seen, the strategy was focused almost exclusively on “behavioural” risk factors typical of Western countries: tobacco, physical exercise, obesity, diet and excess salt. The identification of these priority risk factors is hard to disagree with, but there are serious limits in the 25 × 25 strategy (see the criticism by Pearce et al. 2014). There is evidence of the fact that prevention based on a strictly individualised approach—such as educational messages by healthcare personnel—has an overall limited impact on cancers, whereas actions at the level of the population are more effective, for example taxation for tobacco.

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