Ch 2 Page 3 / 13
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 (see Fundamental Oncology -( in French)

The role of tobacco in the origin of many cancers is clearly demonstrated:

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.

An increased number of the following cancers are also observed among smokers:

These cancers are less frequent among non-smokers than 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).

Poumon_et_tabac.gif (10106 octets)
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:

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).

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 (with its very important psychological burden). Noise is very often provoked by the tactlessness of a few individuals who disturb a whole community (a noisy bike in the night wake an entire city street!).

Cancer prevention - You are looking at website