Several types of studies must be carried out and show concordant results to be able to affirm that an element is carcinogenic. A long and often complex process.
“By changing our lifestyle habits, we can reduce our risk of cancer,” writes on its site. the Léon Bérard center, on the occasion of World Cancer Day, this Saturday, February 4. It is indeed estimated that in France “about 40% of cancers could be avoided by modifying our behavior”.
We know that the consumption of alcohol and tobacco can lead to cancer, just like excessive consumption of red meat, but exposure to other substances present in our environment can also be dangerous. However, being able to avoid or limit our contact with these products, it is still necessary to identify them.
IARC (International Agency for Research on Cancer), a body of the World Health Organization, thus lists in its latest report 122 agents which are proven carcinogens, including opium and tobacco. It lists 93 other “probable” carcinogens and 319 “possible” carcinogens.
The European Union also has a similar classification of substances considered to be carcinogenic. This allows it to regulate or even ban their use and circulation in Europe.
“Possible”, “probable” or “proven” carcinogen?
To carry out this classification, these organizations study the scientific “bundles of evidence” around suspicious substances, explains to BFMTV.com Henri Bastos, scientific director of Health and Work at ANSES (national health security agency).
Their method “will mobilize three types of studies”, explains Béatrice Fervers, associate professor in oncology, head of the cancer prevention and environment department of the Léon Bérard center. There are “epidemiological studies, therefore in humans, experimental studies in laboratory animals, in particular in rodents, and studies in vitro on cell culture, to understand the mechanisms of action”, or laboratory tests.
For a product to be classified as “possible carcinogen“, “we rely on human and/or animal studies, but which are not sufficiently convincing to classify the substance as a proven or probable carcinogen” explains Henri Bastos. “The available information suggests a carcinogenic effect but is not conclusive”, summarizes the IARC.
A substance can be classified at the higher level, “probable carcinogen”with, for example, conclusive studies on two animal species and the first positive epidemiological studies but which have limits, continues Henri Bastos.
the glyphosate is for example considered by the IARC as “probably” carcinogenic, an opinion “based on ‘limited’ evidence of cancer in humans and ‘sufficient’ evidence of cancer in laboratory animals.”
Because even if certain substances have “shown carcinogenic effects in the animal model”, which remains “a strong indication”, it is not enough to decide definitively, notes Béatrice Fervers: the carcinogenic effects observed in animals will not be not necessarily the same in humans.
The category of proven carcinogens, “is used when there is sufficient evidence of carcinogenicity in humans”. “In other words, there is compelling evidence that the agent causes cancer in humans,” says IARC.
And this convincing proof is generally due to the positive results of epidemiological studies which “allow us to observe an association between exposure to a carcinogen and the risk of cancer”, declares Béatrice Fervers. But the road to get there can be long.
Substance = tumor? “Not easy”
First problem, it can be difficult to target the effect of a particular product in a study, because “we are exposed throughout our lives to a whole lot of things” potentially carcinogenic, underlines to BFMTV.com Marc Audebert , research director at INRAE. There are indeed multifactorial causes of cancer: genetic, environmental, dietary, due to lifestyles… In-utero exposure can even be the cause of cancer.
In this sense, “it is not necessarily obvious to have a certain direct causal link: substance = tumor”.
The Tobacco consumption is, for example, associated with several types of cancer. If there are smokers in a cohort, how do you know if their cancer potential is due to the element being evaluated rather than to tobacco? Several epidemiological studies are therefore needed with different, numerous audiences and which present conclusions going in the same direction.
“When we find in different studies, carried out in different countries or contexts, a positive association with this same carcinogen, we have a strong argument”, summarizes Béatrice Fervers.
What exposure to the substance?
There is also the question of the toxicity of a product and the dose to which the population is exposed to it. Marc Audebert takes the example of benzo(a)pyrene, a compound present in coal and oil. This product was singled out for its dangerousness after it was noticed in the United Kingdom that chimney sweeps developed, proportionally, more tumors than the rest of the population.
“Historically, it is by observing populations of workers that we have acquired the most knowledge” on carcinogenic products, explains Henri Bastos.
Indeed, the larger doses “of dangerous substances or compounds and the high frequency at which they can be exposed to them in industry can contribute to the appearance of diseases”, more easily.
If the carcinogenic molecules “are little used and there is therefore a low exposure”, it is much more difficult to identify them, underlines Marc Audebert. But if they do not present an immediate public health problem, it remains important to identify them because one day they could be used in high doses in certain chemical processes.
Sometimes decades before an effect
Another difficulty for scientists: cancer can appear several years after exposure to the carcinogen, even decades. An epidemiological study can therefore “require years” before reaching conclusions, which can be negative, explains Béatrice Fervers.
For all these reasons, patient cohorts are particularly useful to researchers: hundreds, even thousands of people regularly give very diverse data (living places, habits, diet, illnesses, etc.) over several years, which can identify potential carcinogens.
Béatrice Fervers also stresses the need to establish the carcinogenicity of a substance to demonstrate how it can, in the long term, cause cancer. A carcinogen can act by causing a DNA mutation, or chronic inflammation or even have an impact on the immune response of the affected person. And “many, do not act by a single mechanism”, but by “2, 3, 4, 5, 6 or 7” different mechanisms.
“If we don’t find the biological mechanism, we can say that (cancer) may be linked to something else that has not been measured,” says Béatrice Fervers.
“This explains why sometimes, even if we have arguments that tell us ‘there is something there’, we are not necessarily able to decide,” she concludes.
New methods under study
Today, “what is important is to have as much knowledge as possible about the substances placed on the market in order to be able to identify toxic substances”, underlines Henri Bastos. And “the more time passes, the more the level of scientific knowledge increases, which allows us to refine our assessments and adapt the decisions that concern them”.
As the specialist points out, it is not necessary for a product to be classified as a “proven carcinogen” for it to be subject to harsh regulation or a ban, “classification as a presumed carcinogen generally produces the same effects regulations”.
Formaldehyde – notably used in the manufacture of resins – was thus classified as a category 1B carcinogen (i.e. probable carcinogen) in 2014 by the EU, but “in France, employers have had the obligation to seek alternatives since the decree of July 13, 2006”, indicates ANSES.
Researchers are currently working on new methods to identify carcinogenic molecules in our environment. This is the case of Dr. Marc Audebert, who sets up tests to detect more quickly and more certainly the carcinogenic potential of substances and this “without resorting to animal tests”.
