Despite major therapeutic progress over the last twenty years, cancer often remains an incurable disease or leaves many after-effects among cured patients.
However, in about fifty percent of cases, cancer could be nowadays avoided.
This chapter studies such avoidable cancers and the prevention measures to be taken. Cancer prevention is an important new role for physicians in the 21st century. To avoid physicians being considered as moralising or infringing on personal freedom, an active prevention policy should be based on scientific knowledge.
1) Epidemiological data
2) Main causes of cancers
3) Prevention policy
4) Genetic predispositions
5) Genetic counselling
6) Chemoprevention
1) Epidemiological data:
Epidemiological data enables a scientific approach to prevention problems.
Here are some general definitions
Incidence may be calculated according to the formula :
This rate is generally expressed for a population of 100,000 or one million. Incidence rate may be global (confounding all ages) or only concern a given age or part of the population. Since life expectancy varies among continents, this rate can be adjusted to a standardised French population or World population.
Incidence is calculated through population registries.
Mortality is calculated in a similar way by the study of death certificates or population registries which collect this information.
Prevalence is not very important for epidemiology or prevention, but is fundamental for the study of the economical impact of a disease. It enables the estimation of how many patients should be treated per year.
Prevalence (of cancer) is calculated as
We can extrapolate these figures for France.
These figures already enable very simple observations on the number of cancers related to tobacco and alcoholism in our region.
2) Main causes of cancers :
The role of tobacco
Study of cancer incidence gives clear evidence on the factors involved in their origin. These studies are confirmed by biological studies.
The role of tobacco in the origin of many cancers is clearly demonstrated:
A link has been clearly established, through epidemiological and biological studies, between tobacco and the following cancers:
An increased number of the following cancers are also observed among smokers:
Tobacco consumption, particularly cigarettes, is responsible for about 40% of deaths by cancer in our country (France). For heavy smokers (more than 20 cigarettes a day, the risk of lung cancer is multiplied by a factor of 20).
The conclusions of these authors are particularly interesting and frightening :
More than 4,000 chemical products are fond in tobacco smoke. They can be found :
Nicotine is the pharmacological factor of smoking dependency and one of the major nitrosamine products contained in cigarettes. It is present in both inhaled and combustion smoke. It is rapidly absorbed by bronchial epithelia and lung alveoli, but also by oral mucosa. Once it is absorbed, it is quickly carried to specific brain sites where it provokes its dependency action. It is metabolised by the liver as a product called cotinine.
Most experimental animal studies have been carried out with tar from cigarette smoke or extracts from the solid phase of smoke. By these methods, bronchial tumours are easily produced as well as other tobacco-dependent tumours. Nitrosamines ar the most powerful carcinogens.
A mutagenic activity can be demonstrated in the urine of smokers. Modifications of the DNA of peripheral lymphatic cells, as chromatide exchanges, micro-nuclei and adducts are also found in smokers. These adducts are generally situated on the methyl-7 radical of guanine and oxygen-6 of methyl-deoxy-guanosine. Another frequent adduct, specific to nicotine, is found on DNA and haemoglobin.
Xenobiotics (in French) are metabolised by various enzymatic systems localised in microsomes. Some individuals have a very quick metabolism for xenobiotics by cytochrom P 450, under the dependency of CYP2D6 gene. Those subjects may have an increased risk of cancer. However, conversely, we do not know of any protective gene against tobacco cancerogenesis.
What is clear is that mutagenic products issued from the tobacco smoke are found in the urine of non-smoking spouses of heavy smokers. We demonstrated this fact at the Centre François Baclesse, in a very unexpected way: we were studying the toxicity of chemotherapy preparation by the nurses in our cancer clinics (at a time when there were no fume hoods). We discovered that there were more mutagenic products on unworked days (Saturday, Sunday) than on working days, and correlated this phenomenon to the tobacco consumption of the spouse or the nurse herself during this leave period.
Tobacco contains mutagenic genotoxic amines: one single mutation may be responsible for further degeneration.
A cautious approach leads to the protection of non-smoking persons and particularly children. This is accepted and understood more and more by everyone, and even by smokers. It is now forbidden to smoke in Irish pubs, planes and more frequently in trains, and smokers consider these limitations to be useful.
The debate in France is to know if we should adopt the complete exclusion of smokers even in open public places as is often the case in the United States where people leave their building to smoke. In this country, interrupting smoking is part of a community deed to respect others. It is a kind of public-spiritedness which should inspire our French legislators.
In comparison, such public-spiritedness should inspire the protection against noise . Noise is very often provoked by the tactlessness of a few individuals who disturb a whole community.
Occupational cancers :
According to the French Ministry of Employment, occupational cancers may be responsible for around 3% of deaths by cancer.
In the United States, the National Cancer Institute fears higher figures over the next few years in conjunction with the role of asbestos, arsenic, nickel, chrome, benzene and certain oil industry by-products. It is quite possible that these figures (at least in France) are under-evaluated since occupational exposure to carcinogens is associated with other triggering factors (like tobacco and alcohol).
Group 1 - The product is carcinogenic for the human being
The agent (mixture) is carcinogenic to humans. The exposure circumstances involve exposure that is carcinogenic to humans.
For instance: Arsenic and arsenic compounds, Aflatoxins, Benzene, Beryllium and beryllium compounds, Asbestos, Aluminium production, Coal gasification, Coke production, Rubber industry, and so on...
Group 2 - The product is probably carcinogenic for the human being
The agent (mixture) is probably carcinogenic to humans. The exposure circumstances involve exposure that is probably carcinogenic to humans. Carcinogenesis has generally been proven for animal.
For instance: Acrylamide, Benzo[a]pyrene, Benzidine-based dyes, Lead compounds, Vinyl fluoride, beryllium and its compounds.
Group 3 - The product might have a carcinogenic effect for the human being
We only have very limited evidence of such carcinogenic power on humans BUT no real proof of carcinogenicity for animals, or vice-versa.
In this group we find: chlorinated toluene, acrylamide, potassium bromide as well as the various products used for carpentry and woodwork.
Group 4 - The product cannot be classified according to its potential carcinogenicity.
This class includes many products for which no clear information is available.
Group 5 - The product is probably not carcinogenetic for the human being
In this category, we find all the products for which studies show the absence of any carcinogenic power for humans as well as for animals.
Fully aware of the list of the various compounds used in the firm where he (she) works, he (she) must suggest all necessary preventive measures to protect potentially exposed personnel
He (she) also has a major role in informing employees of the potential toxicity of the various compounds. The annual physical examination (possibly more frequent according to the employee’s position) is combined with other specific examinations if necessary.
He (she) establishes a specific certificate (in France this is called a preliminary declaration) of occupational disease.
Two sites are of great interest on the subject : one in French : Institut de Médecine du Travail de l'Université de Rennes (in French) or the Finnish Institute of Occupational Health which publish the CAREX study (look at FIOH and then Collaboration) under the patronage of AIRC .
Radiations and environment:
Environment:
According to many evaluations, around 2% of cancers could be due to environmental causes, but these figures are very approximate, are not backed by any rigorous scientific data and are probably an underestimation of the reality. However, certain claims of great numbers of environmental cancers are also totally void of any scientific epidemiological or biological proof (such as DNA modifications).
The majority of declarations about the ‘appalling” role of atmospheric pollution are mainly related to respiratory diseases (child asthma) or allergies (eczema) but not necessarily cancer.
Unfortunately, (except perhaps as the consequence of a catastrophic event like the Tchernobyl explosion), we may well be unable to prove the role of pollution or environmental factors due to the major toxicity of tobacco and alcohol and their broad use by the earth’s inhabitants.
The majority of the sun’s dangerous rays are captured by the earth’s atmosphere, in particular by the stratospheric ozone layer: cosmic rays, gamma rays, X rays and ultraviolet C rays. The ozone layer only allows rays with a wavelength above 290 nm to pass through.
It is established that holes in the ozone layer are dangerous since they diminish protection against the sun’s rays. However, their apparition is not responsible for the increasing number of skin cancers, since they are mainly observed in areas of low population density. . Interestingly, the reduction of the use of PFC gas is beginning to reduce the formation of holes in the ozone layer.
The increased risk of skin cancer would appear to be correlated to an increase in sunbathing and the overwhelming desire to obtain a good tan without sufficient skin protection. Water reverberation on the sea, snow or ice are further aggressions to our skin, exacerbated by the fact that the cooling effect of the wind or winter temperatures tend to lead us to forget the ever-present burning effect of the sun.
Ultraviolet rays are responsible for two types of skin cancer:
On the contrary, melanomas mainly affect young people, originating in usually unexposed parts of the body (only exposed during sunbathing or surfing for example). People with a blond complexion are at particular risk since they produce less melanin than those with a darker complexion. Therefore, Australians who often have a clear blond complexion (or are red-headed), live in a very sunny climate at equatorial latitudes and are very keen on beach sports, are at great risk, with the highest incidence in the world.
Many very interesting sites (notably from Australia) are dedicated to the prevention of melanoma:
Face workers' are exposed to relatively important irradiation levels. Uranium miners undergo specific medical control.
The main artificial source of irradiation is provoked by physicians through numerous radiological examinations. Thus, as physicians, we should limit our requests to only those examinations offering the quickest and easiest diagnosis, if essential for the patient. Every radiological examination is a disturbance for patients.
Great precaution should be taken to protect doctors and technicians working in radiology units. In the past, we observed many skin tumours induced by excessive exposure to radiation (for instance surgeons reducing a fracture under radioscopy). Leukaemia and sarcomas were also observed.
The effects of the massive irradiation in Hiroshima and Nagasaki during the second world war has been intensely studied by the American military authorities.
The nuclear industry has brought many precautionary measures such as individual surveillance of employees, regular studies of radioactive waste and its potential effect on the surrounding population. (In France, for instance, a dedicated tumour registry has been created in the Manche Department in order to study the potential harm caused by the La Hague recycling nuclear fuel facility). Such prevention of nuclear accidents, and regular training to ensure procedure observance are absolutely necessary.
The Tchernobyl accident clearly demonstrated how the combination of human failure, poor technical
conception and the absence of training for efficient crisis reaction can result in catastrophic situations.
One of the solutions to prevent the risk of thyroid carcinoma (as observed around the Tchernobyl area) is the quick absorption of iodine potassium capsules. Many iodine capsules have been distributed to the French population living around nuclear plants. Their efficiency has been demonstrated (due to the iodine saturation of the thyroid gland). However its practical efficiency may be dubious since such measures should be applied at the very onset of radioactive rejection. Repeated exercises are necessary to ensure that the population correctly apply such measures, however authorities are reluctant to insist on or even suggest the potential danger in living close to a nuclear plant.
Another source of irradiation is frequent high altitude travel by plane. During flights, pilots, cabin crew and passengers are exposed to cosmic rays without the usual ozone filter. Most rays are neutrons and gamma rays. Annual doses around 2 to 5 mSv are quite frequent (and notably for the staff of Concord or those travelling above the polar zones). However, the real impact for flight personal is difficult to evaluate, due to the low number of subjects involved, but also due to other toxic or dangerous habits such as frequent smoking and solar exposure during stopovers.
The irradiation of astronauts during space flight should also be considered and studied.
The difficulty in studying the precise role of small doses of irradiation is noteworthy. In the past, certain authors considered that a small amount of irradiation might stimulate immunity and DNA repair mechanisms. A precise exposure threshold is difficult to define and for this reason systematic precautionary measures should be taken for all potentially exposed personnel.
3) A prevention policy:
In our Cancer Centre in Caen, cancers due to tobacco and alcohol represent half of hospital admissions: lung cancer, head and neck tumours, oesophageal cancer and bladder carcinoma.
These two toxic products also have effects on the cardio-vascular system, the liver, the stomach and nerves.
Contrary to common belief, stopping tobacco or alcohol consumption leads to a rapid and significant reduction in the risk either for cancer or the other related diseases.
The following diagram shows the significant reduction in the risk of lung cancer in relation to stopping smoking and the influence of stopping duration.
It is relatively easy to put together a prevention policy, but strong political action is necessary.
Tobacco consumption
How to help patients to stop smoking :
Specialised stop smoking clinics are managed by physicians having received technical and psychologicaltraining to help dependent patients to regain their liberty. There are more and more of these clinics. According to the French cancer plan, every hospital should have one.
Evaluating tobacco dependency
Before any treatment, the dependency on tobacco and the patient’s motivation to stop smoking should be evaluated.
Many practical scales have been created: here we quote some French scales, many of them used also in English speaking countries :
the Fagerström questionnaire, testing physical dependence on nicotine,
the Horn test, studies the smoking motivations, (F.F. lkard, D.E. Green and D. Horn, A scale to differentiate between types of smoking as related to management of affect. Int J Addict 4 (1969), pp. 649–659),
the Demaria, Grimaldi et Lagrue test is an auto-test to know if an attempt to stop smoking has a good chance of success.
study of smoking habits: number of cigarettes, smoke inhalation measure of carbon monoxide (CO): for the same number of cigarettes, heavy smokers inhaling smoke have a much higher carbon monoxide level than a smoker who lets his(her) cigarette consume on the corner of the ashtray, measure of urinary cotinine, reflecting nicotine addiction.
There are many different reasons behind the desire to stop smoking.
Among them are:
Whatever the initial motivation, stopping smoking is a difficult experience for the smoker. As the Swiss website StopTabac emphasises, it is important to positively formalise the beginning of the quitting phase Stopping smoking necessitates strong will power, so we have to help the patient to combat his (her) nicotine dependency.
They suggest many techniques to eradicate the desire to light up. Lighting up is an urgent need and refusing to do so necessitates great will-power; it doesn’t last long but repeats itself over and over again at the beginning of stopping smoking.
Medical treatment is often useful and, in particular, nicotine substitutes: manipulation of such treatment requires excellent knowledge of its active principles, thus justifying stop smoking clinics.
Other drugs may be used. Clonidine (an anti-hypertension drug) might be useful during the first days of withdrawal. Bupropion LP, an anti-depressant drug, acts by capturing dopamine and noradrenaline at the synapses of the central nervous system. It could be more efficient than nicotine substitutes.
Nicotine dependent smokers may be exposed to very unpleasant or painful withdrawal syndromes: irresistible urge for a cigarette, nervousness, anxiety, irritability, severe concentration difficulties, agitation, insomnia, and so on.
Relapses are quite frequent and should not be considered as a disaster for the smoker. A strategy for renewing abstinence should rapidly be elaborated.
The circle of family and friends is therefore very important in the continuation of tobacco withdrawal.
If stop smoking clinics are not frequently consulted, simple advice may be given by friends or the smoker’s general practitioner. There are no old smokers clubs such as alcoholics anonymous groups.
Are smoking withdrawal techniques efficient?
Results published on the French website TabacNet are very encouraging. However we should underline the necessity for:
strong motivation on the part of the smoker, a competent medical and nursing team to take care of the smoker.
The review by Said S (Essais contrôlés randomisés d'aides médicamenteuses de l'arrêt du tabac - Résultats et perspectives) offers conclusions on the efficiency of nicotine patches and behaviour therapies:
The relationship between alcohol and cancer has never been so clearly demonstrated as that between tobacco and cancer. The fight against alcoholism in cancer prevention has, therefore, always been considered of lesser necessity by physicians.. Moreover, the French society has always been very tolerant towards alcoholics and alcoholism, and alcoholic doctors are not uncommon!
The aim of this page is to sensitise carers about the specificity of alcoholism and about the difficulties that are met by alcohol-dependent people.
The famous 'French exception', which concerns the low mortality rate from cardio-vascular diseases in our country, is widely counterbalanced by excessive alcohol consumption, largely superior to the reputed small after-dinner drink, and this alcoholism is responsible for the increased incidence of certain cancers (such as head and neck cancers in Western France).
Alcohol produces substantial revenue .
The State (not only the French state!) amasses a considerable amount of tax on alcohol. Smuggling is relatively rare in France (not in other countries) despite the disappearance of the famous privilege of home distilling.
Consumption in France is high, but is constantly diminishing.
In Normandy ,l'Observatoire Régional de la Santé (Regional Health Observatory) has given a clear view of
premature deaths due to alcohol: the three major causes of supra-mortality are: head and neck cancer, alcoholic psychoses and suicides.
Alcoholism can be defined as the loss of the capacity to freely abstain from alcohol.
Alcoholic dependency is psychological and physical and results in social dependency.
The reasons for the diversity of reactions to alcohol are unknown: why can certain people drink and then stop drinking whilst others progressively become alcoholic?
The psychology of the alcoholic patient and of his circle of family and friends explains why the patient’s own awareness of his dependency is crucial.. The alcoholic person lies to others and lies to himself by modesty and by shame. He seeks every opportunity to satisfy his need for alcohol. Family and friends protect him, they deny the alcoholism of their parent or friend, despite their own suffering and the potential threat that they endure.
Complete abstinence is the only way to get rid of a very paradoxical body reaction: if there is no alcohol in the body, the need, the urge for alcohol disappears progressively. If the patient drinks only a small glass, the ingested alcohol does not satisfy his need for drinking.
Treatment for alcoholism: always follows the same therapeutic plan: physical withdrawal problems are treated first of all before concentrating on psychological and family problems.
Help through groups like Alcoholics Anonymous or other organisations is essential in satisfying the constant need for psychological support.
4) Genetic Predispositions:
Genetic counselling is a new approach in cancer treatment. Many different aspects should be contemplated in order to adopt a practical attitude. The following recommendations originate from a working group of onco-geneticians from the French Federation of Comprehensive Cancer Centres (Standards, Options and Recommendations ).
Onco-genetic Consultation :
During his study, the onco-genetician will need medical information from certain of the consultant’s relatives. However, it is not possible to contact and all the more so to summon one of the consultant’s relatives without the consultant’s explicit consent. The same restrictions apply for biological sampling. The physician is bound by medical secrecy and cannot write or speak to another member of the family since this implies revealing information about the constultant’s pathology.
French law is very explicit on this subject and similar laws exist almost in every country.
Therefore the initial consultant must remain the contact for other members of his (her) family, asking them to agree (written consent) for a consultation or a blood sample.
For such relatives, it should be possible for them to discuss this approach with a physician near to their residency, in order for them to obtain the best possible information onthe potential consequences of their acceptance.
The person can accept or refuse to know his risks. Each result must be tactfully given with easy to understand vocabulary, and without any interference from other family relatives.
Before accepting the blood test (or receiving the results), the person must be aware of the potential risks, the benefits and the limitations or uncertainties of the test as well as the efficiency of prevention and screening opportunites.
6) Chemo-prevention of cancer:
The long history of a developing cancer shows that many steps are involved between the first initiated cell and metastatic cancer. For every step, it is conceivable that medication taken by subjects at risk of a particular type of cancer might reduce the incidence of this cancer. Clinical studies are difficult to set up: a great number of healthy subjects would be concerned, the medication would need to be of low or no toxicity, it should be easy to deliver andthe result should be demonstrated by randomised studies.
Some studies have given hope for a chemo-prevention of cancer :
However, in about fifty percent of cases, cancer could be nowadays avoided.
This chapter studies such avoidable cancers and the prevention measures to be taken. Cancer prevention is an important new role for physicians in the 21st century. To avoid physicians being considered as moralising or infringing on personal freedom, an active prevention policy should be based on scientific knowledge.
1) Epidemiological data
2) Main causes of cancers
3) Prevention policy
4) Genetic predispositions
5) Genetic counselling
6) Chemoprevention
1) Epidemiological data:
Epidemiological data enables a scientific approach to prevention problems.
Here are some general definitions
Incidence may be calculated according to the formula :
| Number of patients developing a cancer | |
| Incidence = | ----------------------------------------------------------- for a given period of time |
| Total number of persons in the population |
Incidence is calculated through population registries.
Mortality is calculated in a similar way by the study of death certificates or population registries which collect this information.
Prevalence is not very important for epidemiology or prevention, but is fundamental for the study of the economical impact of a disease. It enables the estimation of how many patients should be treated per year.
Prevalence (of cancer) is calculated as
| Number of patients with cancer | |
| Prevalence= | ----------------------------------------------------------- for a given period of time |
| Total number of persons in the population |
Some figures
In our region (Normandy), we are fortunate to have registries in each of the two geographical 'Départements':Calvados and Manche. Scientific data is therefore well adapted to our daily practice.We can extrapolate these figures for France.
Cancer Incidence in Calvados and in France (in French)You also can consult data on cancer incidence and mortality for the world on the International Centre for Research on Cancer (IARC) website. The data shows major variations from one country to another and the importance of standardising results according to the spontaneous mortality of each region.
Number of annual cancers and cancer mortality in France (in French)
Incidence of male cancers in Europe
Incidence of female cancers in Europe
These figures already enable very simple observations on the number of cancers related to tobacco and alcoholism in our region.
2) Main causes of cancers :
The role of tobacco
Study of cancer incidence gives clear evidence on the factors involved in their origin. These studies are confirmed by biological studies.
The role of tobacco in the origin of many cancers is clearly demonstrated:
- by epidemiological studies,
- by the study of smoke composition,
- by the discovery of specific genetic lesions of tumour and normal cells of smokers,
- by the growing body of knowledge about the metabolism of tobacco amines.
The epidemiological studies
Tobacco is nowadays the most important cause of cancer.A link has been clearly established, through epidemiological and biological studies, between tobacco and the following cancers:
These cancers are rare among non-smokers.
- lung,
- larynx,
- oral cavity
- pharynx,
- oesophagus,
- bladder.
An increased number of the following cancers are also observed among smokers:
These cancers are less frequent among non-smokers than among smokers.
- pancreas,
- kidney,
- cervix uteri,
- rhino pharynx,
- stomach,
- leukaemia.
Tobacco consumption, particularly cigarettes, is responsible for about 40% of deaths by cancer in our country (France). For heavy smokers (more than 20 cigarettes a day, the risk of lung cancer is multiplied by a factor of 20).
 |
| Relation between tobacco consumption and the risk of lung cancers |
Doll et Peto Studies
A great number of studies have been carried out and published by two English researchers, R. Doll and R. Peto on the tobacco consumption of British physicians. Their study began in 1951. An update of their results was published in 2001 in the British Medical Journal. We give details of their study on a specific page on prevention.The conclusions of these authors are particularly interesting and frightening :
About half of the smokers who do not stop will die from their tobacco habit,
About a fourth of smokers who do not stop will be dead before they reach the age of 70.
To correctly understand the full effect of tobacco consumption needs up to 50 years of observation,
Men born during the first decades of the 20th century are the first population in which the toxic effect of tobacco could be expressed over a lifetime,
Only non-smokers have truly benefited from medical progress with a rapid increase in life expectancy: smokers die, as a mean, 10 years earlier than non-smokers.
Smokers who stop between the age of 30 and 40 reduce almost totally this increased mortality .
The composition of cigarette smoke
Plus de 4.000 produits chimiques sont retrouvés au niveau de la fumée du tabac. Ils peuvent s'observer :More than 4,000 chemical products are fond in tobacco smoke. They can be found :
The majority of carcinogenic products are found in the solid phase. 43 carcinogens have been perfectly identified. Among them:
- either in the gas phase
- or in suspension, in the solid phase.
Nitrosamines are among the most toxic: they are found in the inhaled smoke in the smoker’s lungs, but also in the external smoke produced by the slow combustion of the cigarette, possibly at a higher concentration than inhaled smoke (passive smoking).
- Polycyclic aromatic hydrocarbons,
- Nitrosamines,
- Heterocyclic hydrocarbons,
- benzene,
- radioactive 210-polonium.
Nicotine is the pharmacological factor of smoking dependency and one of the major nitrosamine products contained in cigarettes. It is present in both inhaled and combustion smoke. It is rapidly absorbed by bronchial epithelia and lung alveoli, but also by oral mucosa. Once it is absorbed, it is quickly carried to specific brain sites where it provokes its dependency action. It is metabolised by the liver as a product called cotinine.
Markers of genetic toxicity
Cigarette smoke contains tumour initiating and promoting agents. The initiating products are mutagens which build covalent links to cellular DNA: their effect is potentially irreversible. Promoting agents stimulate excessive proliferation of initiated cells.Most experimental animal studies have been carried out with tar from cigarette smoke or extracts from the solid phase of smoke. By these methods, bronchial tumours are easily produced as well as other tobacco-dependent tumours. Nitrosamines ar the most powerful carcinogens.
A mutagenic activity can be demonstrated in the urine of smokers. Modifications of the DNA of peripheral lymphatic cells, as chromatide exchanges, micro-nuclei and adducts are also found in smokers. These adducts are generally situated on the methyl-7 radical of guanine and oxygen-6 of methyl-deoxy-guanosine. Another frequent adduct, specific to nicotine, is found on DNA and haemoglobin.
Genetic variation of susceptibility to cancer
Certain families are known to be prone to lung cancer, for which the occurrence seems to be earlier in comparison with other patients with a similar tobacco consumption.Xenobiotics (in French) are metabolised by various enzymatic systems localised in microsomes. Some individuals have a very quick metabolism for xenobiotics by cytochrom P 450, under the dependency of CYP2D6 gene. Those subjects may have an increased risk of cancer. However, conversely, we do not know of any protective gene against tobacco cancerogenesis.
Passive smoking
Many epidemiological studies raise the suspicion of the harmfulness of passive smoking. Some recent studies are not so demonstrative or bring to the fore only minimal risks. Most of these studies are case control studies comparing non-smoking patients with lung cancer sufferers (independently of the histological type) and are based on a small number of cases.What is clear is that mutagenic products issued from the tobacco smoke are found in the urine of non-smoking spouses of heavy smokers. We demonstrated this fact at the Centre François Baclesse, in a very unexpected way: we were studying the toxicity of chemotherapy preparation by the nurses in our cancer clinics (at a time when there were no fume hoods). We discovered that there were more mutagenic products on unworked days (Saturday, Sunday) than on working days, and correlated this phenomenon to the tobacco consumption of the spouse or the nurse herself during this leave period.
Tobacco contains mutagenic genotoxic amines: one single mutation may be responsible for further degeneration.
A cautious approach leads to the protection of non-smoking persons and particularly children. This is accepted and understood more and more by everyone, and even by smokers. It is now forbidden to smoke in Irish pubs, planes and more frequently in trains, and smokers consider these limitations to be useful.
The debate in France is to know if we should adopt the complete exclusion of smokers even in open public places as is often the case in the United States where people leave their building to smoke. In this country, interrupting smoking is part of a community deed to respect others. It is a kind of public-spiritedness which should inspire our French legislators.
In comparison, such public-spiritedness should inspire the protection against noise . Noise is very often provoked by the tactlessness of a few individuals who disturb a whole community.
Occupational cancers :
According to the French Ministry of Employment, occupational cancers may be responsible for around 3% of deaths by cancer.
In the United States, the National Cancer Institute fears higher figures over the next few years in conjunction with the role of asbestos, arsenic, nickel, chrome, benzene and certain oil industry by-products. It is quite possible that these figures (at least in France) are under-evaluated since occupational exposure to carcinogens is associated with other triggering factors (like tobacco and alcohol).
Responsibility of chemical products
The International Agency for Research on Cancer (IARC) classifies chemical products and manufacturing techniques according to 5 internationally recognised categories depending on their potential carcinogenic power:Group 1 - The product is carcinogenic for the human being
The agent (mixture) is carcinogenic to humans. The exposure circumstances involve exposure that is carcinogenic to humans.
For instance: Arsenic and arsenic compounds, Aflatoxins, Benzene, Beryllium and beryllium compounds, Asbestos, Aluminium production, Coal gasification, Coke production, Rubber industry, and so on...
Group 2 - The product is probably carcinogenic for the human being
The agent (mixture) is probably carcinogenic to humans. The exposure circumstances involve exposure that is probably carcinogenic to humans. Carcinogenesis has generally been proven for animal.
For instance: Acrylamide, Benzo[a]pyrene, Benzidine-based dyes, Lead compounds, Vinyl fluoride, beryllium and its compounds.
Group 3 - The product might have a carcinogenic effect for the human being
We only have very limited evidence of such carcinogenic power on humans BUT no real proof of carcinogenicity for animals, or vice-versa.
In this group we find: chlorinated toluene, acrylamide, potassium bromide as well as the various products used for carpentry and woodwork.
Group 4 - The product cannot be classified according to its potential carcinogenicity.
This class includes many products for which no clear information is available.
Group 5 - The product is probably not carcinogenetic for the human being
In this category, we find all the products for which studies show the absence of any carcinogenic power for humans as well as for animals.
Characteristics of occupational cancers
There are generally no specific medical characteristics of occupational cancers, and most of the usual symptoms are found:- very long latency between occupational exposure and the apparition of cancer,
- no specific histology for occupational cancer,
- simultaneous action of other carcinogenic products like tobacco and alcohol.
- Very often, the clinical diagnosis is made well after the patient’s exposed work period, and for this reason, the etiologic diagnosis is difficult,
- There may be several simultaneous or consecutive exposures to a variety of carcinogenic products. Manufacturing methods are developing processes, and it is often difficult, 10 to 30 years later, to establish a precise history of the worker's exposure to toxic products. The great mobility of employees and the precariousness of jobs add further difficulty.
- The number of workers exposed to a potential danger may be very low, thus rendering epidemiological studies difficult,
- We do not possess many cancer registries specifically dedicated to the industrial employment of cancer patients and which involve the collection of patient activities,
- Many other factors may obscure the situation, with known etiological factors like tobacco, alcohol and diet.
Main recognised occupational cancer
(this chapter is according to French legislation)| Kind of work | Carcinogenetic product | Tumour |
| Colouring, rubber | Aromatic amines | Bladder |
| Chemical industry | Benzene | Leukaemia, myelo-proliferating syndromes |
| Asbestos Industry | Asbestos | Mesothelioma |
| Cadmium Industry | Cadmium | Prostate |
| Chemical Industry | Chrome | Lung |
| Chemical Industry | Nitrous products | Glioblastoma |
| Mining Industry | Iron Oxide | Lung |
| Various activities | Nickel | Sinuses, Bronchial carcinoma |
| Various activities | Arsenic | Skin cancers, liver angiosarcoma, lung |
| Plastic industry | Vinyle Chloride | Liver angiosarcoma |
| Radiation | Radiation | Lung, leukaemia, osteosarcoma |
| Cole, asphalt, petrochemistry | Polycyclic hydrocarbons | Skin, Lung, bladder |
| Farmers, sailors | Ultra-Violet rays | Skin, lips |
| Wood and leather workers | Tanning products | Noose sinus, ethmoid |
Role of the occupational physician
The occupational physician plays a major role in the detection and screening of occupational cancers.Fully aware of the list of the various compounds used in the firm where he (she) works, he (she) must suggest all necessary preventive measures to protect potentially exposed personnel
He (she) also has a major role in informing employees of the potential toxicity of the various compounds. The annual physical examination (possibly more frequent according to the employee’s position) is combined with other specific examinations if necessary.
He (she) establishes a specific certificate (in France this is called a preliminary declaration) of occupational disease.
Role of the General Practitioner for retired persons
The knowledge of previous occupational exposure should be an indication for specific screening measures for neoplastic diseases (or others) after retirement (the latency period for cancer could be as long as 20 years).Two sites are of great interest on the subject : one in French : Institut de Médecine du Travail de l'Université de Rennes (in French) or the Finnish Institute of Occupational Health which publish the CAREX study (look at FIOH and then Collaboration) under the patronage of AIRC .
Radiations and environment:
Environment:
According to many evaluations, around 2% of cancers could be due to environmental causes, but these figures are very approximate, are not backed by any rigorous scientific data and are probably an underestimation of the reality. However, certain claims of great numbers of environmental cancers are also totally void of any scientific epidemiological or biological proof (such as DNA modifications).
The majority of declarations about the ‘appalling” role of atmospheric pollution are mainly related to respiratory diseases (child asthma) or allergies (eczema) but not necessarily cancer.
Unfortunately, (except perhaps as the consequence of a catastrophic event like the Tchernobyl explosion), we may well be unable to prove the role of pollution or environmental factors due to the major toxicity of tobacco and alcohol and their broad use by the earth’s inhabitants.
Sun radiations
Sun is the most important source of ionising radiation by ultraviolet rays.The majority of the sun’s dangerous rays are captured by the earth’s atmosphere, in particular by the stratospheric ozone layer: cosmic rays, gamma rays, X rays and ultraviolet C rays. The ozone layer only allows rays with a wavelength above 290 nm to pass through.
It is established that holes in the ozone layer are dangerous since they diminish protection against the sun’s rays. However, their apparition is not responsible for the increasing number of skin cancers, since they are mainly observed in areas of low population density. . Interestingly, the reduction of the use of PFC gas is beginning to reduce the formation of holes in the ozone layer.
The increased risk of skin cancer would appear to be correlated to an increase in sunbathing and the overwhelming desire to obtain a good tan without sufficient skin protection. Water reverberation on the sea, snow or ice are further aggressions to our skin, exacerbated by the fact that the cooling effect of the wind or winter temperatures tend to lead us to forget the ever-present burning effect of the sun.
Ultraviolet rays are responsible for two types of skin cancer:
Epidermal cancers generally affect older people or workers who are regularly exposed to the sun, like farmers and fishermen. The most affected parts of the body are those exposed to the sun on a daily basis, for example the face and the chest. Surgical removal or local contact radiotherapy are very efficient. Spinal cell carcinoma, in rare neglected cases, may metastase and become lethal.
- epidermal carcinoma (either basal cell carcinoma or spinal cell carcinoma) which is the most frequent but is generally not dangerous if treated early,
- melanoma (5 - 6,000 new patients in France each year), for which early diagnosis (or systematic screening) and complete removal are the only guarantees of cure.
On the contrary, melanomas mainly affect young people, originating in usually unexposed parts of the body (only exposed during sunbathing or surfing for example). People with a blond complexion are at particular risk since they produce less melanin than those with a darker complexion. Therefore, Australians who often have a clear blond complexion (or are red-headed), live in a very sunny climate at equatorial latitudes and are very keen on beach sports, are at great risk, with the highest incidence in the world.
Hereditary diseases
A few particular hereditary diseases predispose to more or less generalised skin cancers :Xeroderma pigmentosum
Cockayne Syndrom
Prevention of skin cancers consists:
- in educating the general public on the potential dangers of the sun, of prolonged sunbathing and the regular examination of moles(nevus).
- in educating physicians (notably general practitioners) and other carers on the regular examination of their patients’ entire skin, insisting that they be very precise in their diagnosis (using ABCDE rules for melanoma)
- in the regular use of protection against the sun’s rays: spontaneous protection or use of protecting sun cream.
Many very interesting sites (notably from Australia) are dedicated to the prevention of melanoma:
SunSmart
Licensed practical nurse
Ionizing radiations
We are all subject to natural irradiation to which human activity adds some artificial irradiation sources.Face workers' are exposed to relatively important irradiation levels. Uranium miners undergo specific medical control.
The main artificial source of irradiation is provoked by physicians through numerous radiological examinations. Thus, as physicians, we should limit our requests to only those examinations offering the quickest and easiest diagnosis, if essential for the patient. Every radiological examination is a disturbance for patients.
Great precaution should be taken to protect doctors and technicians working in radiology units. In the past, we observed many skin tumours induced by excessive exposure to radiation (for instance surgeons reducing a fracture under radioscopy). Leukaemia and sarcomas were also observed.
The effects of the massive irradiation in Hiroshima and Nagasaki during the second world war has been intensely studied by the American military authorities.
The nuclear industry has brought many precautionary measures such as individual surveillance of employees, regular studies of radioactive waste and its potential effect on the surrounding population. (In France, for instance, a dedicated tumour registry has been created in the Manche Department in order to study the potential harm caused by the La Hague recycling nuclear fuel facility). Such prevention of nuclear accidents, and regular training to ensure procedure observance are absolutely necessary.
The Tchernobyl accident clearly demonstrated how the combination of human failure, poor technical
conception and the absence of training for efficient crisis reaction can result in catastrophic situations.
One of the solutions to prevent the risk of thyroid carcinoma (as observed around the Tchernobyl area) is the quick absorption of iodine potassium capsules. Many iodine capsules have been distributed to the French population living around nuclear plants. Their efficiency has been demonstrated (due to the iodine saturation of the thyroid gland). However its practical efficiency may be dubious since such measures should be applied at the very onset of radioactive rejection. Repeated exercises are necessary to ensure that the population correctly apply such measures, however authorities are reluctant to insist on or even suggest the potential danger in living close to a nuclear plant.
Another source of irradiation is frequent high altitude travel by plane. During flights, pilots, cabin crew and passengers are exposed to cosmic rays without the usual ozone filter. Most rays are neutrons and gamma rays. Annual doses around 2 to 5 mSv are quite frequent (and notably for the staff of Concord or those travelling above the polar zones). However, the real impact for flight personal is difficult to evaluate, due to the low number of subjects involved, but also due to other toxic or dangerous habits such as frequent smoking and solar exposure during stopovers.
The irradiation of astronauts during space flight should also be considered and studied.
The difficulty in studying the precise role of small doses of irradiation is noteworthy. In the past, certain authors considered that a small amount of irradiation might stimulate immunity and DNA repair mechanisms. A precise exposure threshold is difficult to define and for this reason systematic precautionary measures should be taken for all potentially exposed personnel.
3) A prevention policy:
Why should we set up a prevention policy?
For most cancer types with a specific tobacco origin as described in the previous pages (mainly in relation to tobacco and alcohol)In most cases, diagnosis is late and cancer is no longer localised.
- either the cancer is still localised but major mutilation is necessary to save the patient (pneumonectomy for lung cancer which can be carried out in only 10% of cases, total laryngectomy which cures about 50% of patients, but with voice loss and the risk of social isolation, oesophagectomy which cures only 10% of patients and radical cystectomy with an external derivation in about half of cases),
- or the cancer is no longer localised: only palliative measures can be taken in order to win time (palliative radiotherapy, chemotherapy with a few short-lived responses and pain sedation).
In our Cancer Centre in Caen, cancers due to tobacco and alcohol represent half of hospital admissions: lung cancer, head and neck tumours, oesophageal cancer and bladder carcinoma.
These two toxic products also have effects on the cardio-vascular system, the liver, the stomach and nerves.
Contrary to common belief, stopping tobacco or alcohol consumption leads to a rapid and significant reduction in the risk either for cancer or the other related diseases.
The following diagram shows the significant reduction in the risk of lung cancer in relation to stopping smoking and the influence of stopping duration.
 |
| Effect of stopping smoking on the relative risk of cancer (from Doll and Peto studies). |
- Tobacco consumption is a social reality which can be studied scientifically. In France, like in many other countries, tobacco consumption can be measured, thus allowing a statistical study of the effects of advertisement campaigns paid by the tobacco industry as well as the real impact of prevention propaganda. The economical interest (in French) is colossal. For the French speaking population, two sites are of great interest and defend the interests of the tobacco industry: CDIT and SEITA . For English speakers, the Philip Morris site is also very interesting. These sites are the proof of the difficulty to fight against tobacco consumption.
- Tobacco smoking sociology (in French) has been described in many papers and we have taken the data from a consensus conference in France held in October 1998.
- Tobacco smoking is a health problem like many others. Thus, the physician (or the nurse) should treat this problem like any other: personal history of the smoking habit (beginning, quantities of tobacco smoked, attempts to stop), family and social history (smoking habits of family and friends), disease symptoms (head and neck, lung, heart, vascular disease), physical and psychological dependency, emotional relationships and personal conceptions concerning his (her) own smoking habit. The Swiss website Stop-Tabac (with its English text) is very interesting and helps understand what kind of health problem smoking is.
- The physician is a scientist and has a great deal of epidemiological and experimental proof of the toxicity of tobacco .For the long term benefit of his (her) patient, stopping smoking is very important. Thus, as demanded by ethical principles, the physician (or the nurse) should set aside his (her) own philosophy and attitude towards tobacco in order to act as a genuine health professional. Cigarette smoking by the physician or the nurse (and worse so if done in front of the patient) is a counter-example for adolescents or fragile patients.
- Despite many technical progresses like the new chemotherapies or target therapies, . For instance, the diagnosis of lung cancer or oesophageal cancer is almost always done at an advanced stage when an efficient therapy is no more feasible. Only prevention is efficient.Despite great technical progress such as new chemotherapies or target therapies, most tobacco cancers kill their host. For instance, the diagnosis of lung cancer or oesophageal cancer is almost always at an advanced stage when efficient therapy is no longer feasible. Only prevention is efficient.
- Tobacco smoking is like a drug habit (in French), with its physical and psychological dependency. It is totally wrong to believe that one can stop smoking without any major difficulty. Young people get the habit through multiple and repeated experiences: on the other hand, the social role of smoking is very important.
- Advertising of tobacco links cigarettes to success at work, power of seduction and team spirit. In our times of loneliness and unemployment, cigarettes allow distancing from real situations. This false protection may explain the increasing number of women smokers (at least in France). Fighting advertisement for tobacco smoking is a very efficient preventive measure.
How to help patients to stop smoking :
Specialised clinics
Helping a heavy smoker to stop smoking is a difficult task. Companions friends or general practitioners are often the first people to prompt smokers to stop , but most of the time without any success.Specialised stop smoking clinics are managed by physicians having received technical and psychologicaltraining to help dependent patients to regain their liberty. There are more and more of these clinics. According to the French cancer plan, every hospital should have one.
Evaluating tobacco dependency
Before any treatment, the dependency on tobacco and the patient’s motivation to stop smoking should be evaluated.
Many practical scales have been created: here we quote some French scales, many of them used also in English speaking countries :
the Fagerström questionnaire, testing physical dependence on nicotine,
the Horn test, studies the smoking motivations, (F.F. lkard, D.E. Green and D. Horn, A scale to differentiate between types of smoking as related to management of affect. Int J Addict 4 (1969), pp. 649–659),
the Demaria, Grimaldi et Lagrue test is an auto-test to know if an attempt to stop smoking has a good chance of success.
The magnitude of nicotine dependency
Another way to study tobacco consumption and the potential difficulties in stopping smoking is to study three clinical symptoms :study of smoking habits: number of cigarettes, smoke inhalation measure of carbon monoxide (CO): for the same number of cigarettes, heavy smokers inhaling smoke have a much higher carbon monoxide level than a smoker who lets his(her) cigarette consume on the corner of the ashtray, measure of urinary cotinine, reflecting nicotine addiction.
The scientific study of tobacco dependency enables carers to present a logical programme for quitting.
Conditions for stopping smoking
Just as there is no typical smoker, there is no one best way to stop smoking.There are many different reasons behind the desire to stop smoking.
Among them are:
- following a pathological state caused by tobacco,
- following minor lung problems and due to fear of cancer,
- following short of breath experience when practising sport,
- following an emotional shock (death of a parent or a friend due to a tobacco related disease),
- after becoming aware of the loss of one's liberty due to tobacco dependency,
- for economical reasons (particularly for young people),
- at the beginning of pregnancy,
- when renewing prescription for a contraceptive pill,
- after comments from children,
- when children have pulmonary disease like asthma,
- when the person’s GP discusses the risks of tobacco, when consulting for another reason
- during consultation for a depressive mood or alcoholic consumption.
Whatever the initial motivation, stopping smoking is a difficult experience for the smoker. As the Swiss website StopTabac emphasises, it is important to positively formalise the beginning of the quitting phase Stopping smoking necessitates strong will power, so we have to help the patient to combat his (her) nicotine dependency.
The steps involved in stopping smoking
Most smokers go through 5 phases when they stop smoking:
- hesitation: ’What if I tried to stop smoking?',
- gradual decision to stop smoking during the preceding months,
- immediate mental preparation to stop in the next few days
- stopping action over the first six months,
- reinforcement of the decision after the initial intensive efforts,
The first days
The first days are the worst for the smoker. Most stop smoking clinics give sets of easy advice in order for the smoker to recognise the specific circumstances in which lighting a cigarette has become a reflex.They suggest many techniques to eradicate the desire to light up. Lighting up is an urgent need and refusing to do so necessitates great will-power; it doesn’t last long but repeats itself over and over again at the beginning of stopping smoking.
Medical treatment is often useful and, in particular, nicotine substitutes: manipulation of such treatment requires excellent knowledge of its active principles, thus justifying stop smoking clinics.
Other drugs may be used. Clonidine (an anti-hypertension drug) might be useful during the first days of withdrawal. Bupropion LP, an anti-depressant drug, acts by capturing dopamine and noradrenaline at the synapses of the central nervous system. It could be more efficient than nicotine substitutes.
Nicotine dependent smokers may be exposed to very unpleasant or painful withdrawal syndromes: irresistible urge for a cigarette, nervousness, anxiety, irritability, severe concentration difficulties, agitation, insomnia, and so on.
Relapses are quite frequent and should not be considered as a disaster for the smoker. A strategy for renewing abstinence should rapidly be elaborated.
Pursuing the no tobacco period
Everyone has a friend who has stopped smoking over and over again and has relapsed just as often!The circle of family and friends is therefore very important in the continuation of tobacco withdrawal.
If stop smoking clinics are not frequently consulted, simple advice may be given by friends or the smoker’s general practitioner. There are no old smokers clubs such as alcoholics anonymous groups.
Therapeutic results
Stopping tobacco smoking is very important for the health of our patients even if they are relatively oldAre smoking withdrawal techniques efficient?
Results published on the French website TabacNet are very encouraging. However we should underline the necessity for:
strong motivation on the part of the smoker, a competent medical and nursing team to take care of the smoker.
The meta-analysis by Lam (Meta-analysis of randomised controlled trials of nicotine chewing-gum) demonstrates the importance of a specialised team and of the use of nicotine substitutes (gums) : :
Place of treatment | Subjects | Observation time | Non smokers with placebo | Non smokers with gums |
| Specialised centre | n= 734 | 6 months | 18% | 27% |
| General practitioner | n= 1022 | 6 months | 12% | 11% |
| References | Subjects | Behaviour Duration | Other treatment | Non smokers with placebo | Non smokers with patch |
| Tonnessen 91 | 289 | 16 | - | 2% | 11% |
| Russel 93 | 600 | 18 | advices + book | 5% | 9% |
| Buckremer 89 | 131 | | behavioral therapy | 18% | 26% |
Helping to reduce alcohol dependency:
The relationship between alcohol and cancer has never been so clearly demonstrated as that between tobacco and cancer. The fight against alcoholism in cancer prevention has, therefore, always been considered of lesser necessity by physicians.. Moreover, the French society has always been very tolerant towards alcoholics and alcoholism, and alcoholic doctors are not uncommon!
The aim of this page is to sensitise carers about the specificity of alcoholism and about the difficulties that are met by alcohol-dependent people.
The famous 'French exception', which concerns the low mortality rate from cardio-vascular diseases in our country, is widely counterbalanced by excessive alcohol consumption, largely superior to the reputed small after-dinner drink, and this alcoholism is responsible for the increased incidence of certain cancers (such as head and neck cancers in Western France).
Alcohol produces substantial revenue .
The State (not only the French state!) amasses a considerable amount of tax on alcohol. Smuggling is relatively rare in France (not in other countries) despite the disappearance of the famous privilege of home distilling.
Consumption in France is high, but is constantly diminishing.
In Normandy ,l'Observatoire Régional de la Santé (Regional Health Observatory) has given a clear view of
premature deaths due to alcohol: the three major causes of supra-mortality are: head and neck cancer, alcoholic psychoses and suicides.
Alcoholism can be defined as the loss of the capacity to freely abstain from alcohol.
Alcoholic dependency is psychological and physical and results in social dependency.
The reasons for the diversity of reactions to alcohol are unknown: why can certain people drink and then stop drinking whilst others progressively become alcoholic?
The psychology of the alcoholic patient and of his circle of family and friends explains why the patient’s own awareness of his dependency is crucial.. The alcoholic person lies to others and lies to himself by modesty and by shame. He seeks every opportunity to satisfy his need for alcohol. Family and friends protect him, they deny the alcoholism of their parent or friend, despite their own suffering and the potential threat that they endure.
Complete abstinence is the only way to get rid of a very paradoxical body reaction: if there is no alcohol in the body, the need, the urge for alcohol disappears progressively. If the patient drinks only a small glass, the ingested alcohol does not satisfy his need for drinking.
Treatment for alcoholism: always follows the same therapeutic plan: physical withdrawal problems are treated first of all before concentrating on psychological and family problems.
Help through groups like Alcoholics Anonymous or other organisations is essential in satisfying the constant need for psychological support.
4) Genetic Predispositions:
Some types of cancer have an evident genetic context.
General remarks
Cancer is a continuum of gene modifications and of their expression. The awareness of genetic predisposition for a given patient has three main consequences:- Individuals with a predisposition to develop cancers constitute a high cancer risk for whom specific prevention and systematic screening are available, even if such screening involves complicated procedures.
- The existence of a genetic predisposition is also a ressource for the study of the succession of genetic modifications involved during the development of cancer. Familial forms of cancer are not very frequent, but the usual forms (non familial forms) are often very similar to the familial forms when considering genetic modifications. Therefore, studying familial forms constitutes a major step towards improved understandingof usual forms of cancer.
- In many cases, the predisposition for cancer is accompanied by other development defects in other tissues, thus permitting improved understanding of the physiological role of the modified genes.
We will study:
the familial colon carcinoma,
the familial mammary and ovarian carcinoma,
the familial endocrine cancers,
the particular forms of some child cancers.
We will then study how to institute genetic counselling and an onco-genetic consultation.
5) Genetic counselling :
Goals
The goals of the onco-genetic consultations are:
- evaluating a possible hereditary cancer risk with an aim to either confirm or invalidate it,,
- offering, when possible, a realistic screening policy adapted to the cancer risk,
- offering, when indicated and feasible, molecular research on predisposing genes, whilst explaining the interest and limits of such research,
- taking charge of the psychological consequences of a presumed or demonstrated hereditary risk,
- providing long term follow-up for individuals and families.
Indications
As a general rule, families for which a onco-genetic study is indicated are those with one of the following clinical presentations:
- presence of at least three cases of cancer (for instance: breast, colon) in first or second degree related family members, in the same parental lineage,
- presence of two cases of cancer in first degree related family, associated with at least one of the following criterion:
- early occurrence of one of these cancers, in comparison with the mean age of occurrence (for instance breast cancer before 40 years, colon before 50 years),
- bilateral occurrence (for breast cancers),
- multifocal occurrence ,
- occurrence of several cases of cancer in the same person (multiple primitive tumour syndromes), apart from evident iatrogenic contexts (such as tobacco-related cancers),
- cancer associated with a predisposing disease (like familial colic polypomatosis, Recklinghausen disease, and so on…) or with a dysmorphic syndrome.
Onco-genetic Consultation :
Study of the family
The initial consultant is the indispensable go-between for other members of the family.During his study, the onco-genetician will need medical information from certain of the consultant’s relatives. However, it is not possible to contact and all the more so to summon one of the consultant’s relatives without the consultant’s explicit consent. The same restrictions apply for biological sampling. The physician is bound by medical secrecy and cannot write or speak to another member of the family since this implies revealing information about the constultant’s pathology.
French law is very explicit on this subject and similar laws exist almost in every country.
Therefore the initial consultant must remain the contact for other members of his (her) family, asking them to agree (written consent) for a consultation or a blood sample.
For such relatives, it should be possible for them to discuss this approach with a physician near to their residency, in order for them to obtain the best possible information onthe potential consequences of their acceptance.
Communication of biological results
For every member of the family, the communication of biological results (confirming whether or not the person bears the genetic abnormality rendering him/her more sensitive to cancer?) must be given after a formal written informed consent.The person can accept or refuse to know his risks. Each result must be tactfully given with easy to understand vocabulary, and without any interference from other family relatives.
Before accepting the blood test (or receiving the results), the person must be aware of the potential risks, the benefits and the limitations or uncertainties of the test as well as the efficiency of prevention and screening opportunites.
Therapeutic Options
Three attitudes are technically feasible:However such a family investigation brings with it a lot of anxiety and guilt, with problems in knowing if and how to contact other members of the family (more specifically if the family is broken up).
- Do nothing at all (if no feasible prevention or only recommendations exist): this leaves a doubt on the benefit of carrying out the test.
- Propose systematic screening (at established intervals): for example systematic colonoscopies, mammographies, PSA or Ca 125 blood tests,
- Propose a preventive surgery (breast, ovary, colon) the efficiency of which has been demonstrated for familial polypomatosis of colon, but also more recently for breast or ovarian carcinoma.
6) Chemo-prevention of cancer:
The long history of a developing cancer shows that many steps are involved between the first initiated cell and metastatic cancer. For every step, it is conceivable that medication taken by subjects at risk of a particular type of cancer might reduce the incidence of this cancer. Clinical studies are difficult to set up: a great number of healthy subjects would be concerned, the medication would need to be of low or no toxicity, it should be easy to deliver andthe result should be demonstrated by randomised studies.
Some studies have given hope for a chemo-prevention of cancer :
- Administration of tamoxifen (anti-oestrogen) in the prevention of breast carcinoma among healthy women with important familial risks: the results were positive in one major American study (NSABP Breast Cancer Prevention Trial P-1) and negative in two European studies (IBIS-1 study and Royal Marsden Hospital trial)
- Administration of another anti-oestrogen (raloxifen) used for prevention of osteoporosis in post-menopausal women or CORE trial with positive effect in the prevention of endometrial adenocarcinoma (ASCO 2005).
- Administration of an anti-androgen (finasteride) for the prevention of prostate cancer (see the paper in N Engl J Med, 2003, 349, 3, 213)
- Administration of non steroidal anti-inflammatory drugs or aspirin for the prevention of colon carcinoma,
- Multiple disappointing studies with retinoids for the prevention of head and neck cancer.
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