For a long time, pancreatic cancer was one of those cancers that people didn’t even bother to confirm. Once the outward signs of the disease were identified, doctors would simply send their patients home. What was the point of operating on them to look for growths that would kill them anyway? These tumors are sneaky: they grow silently, lurking deep in the guts. By the time they appear, it’s already too late.
Since the 1990s, advances in imaging and medical analysis have made checks more frequent. A snapshot and a few reagents in test tubes now make it possible to rule out hasty conclusions and characterize the progress of the disease. But due to the lack of sufficiently early diagnosis, the prognosis has not improved. Worse, the victims continue to pile up at an ever-increasing rate, without anyone knowing why.
Although still relatively rare, pancreatic cancer is even about to become the second leading cause of cancer death in France and the United States, according to current trends recorded by health authorities. It was only the fourth leading cause about ten years ago. Neither the chances of survival, around 10% at five years, nor the nature of the tumor, most often a “ductal adenocarcinoma”, have changed. The only new thing is that the disease is increasingly common, even among those under 50, who are usually spared from tumors.
First victim: France
A global phenomenon, unexplained, and particularly visible in developed countries. In the United States, where a study just published in The Lancet has just revived concerns, the annual incidence has jumped by 13% in thirty years. The dynamic is even more marked in France, where the increase reaches 20%. Expressed in number of annual cases, the evolution is even more striking: they are now 330% more frequent in France. Confirmed by study after study, these dire statistics have not escaped the attention of learned societies and health agencies. In France alone, the Academy of Surgery, the Academy of Medicine, the National Cancer Institute, Public Health France, and even the French Cancer Society have issued repeated warnings over the last ten years. “This is one of the developments that worries us the most,” emphasizes its president, Manuel Rodrigues, an oncology researcher.
A common culprit, smoking remains one of the leading known causes of this tumor – it accounts for about 20% of the risk – but it does not explain the current trend, because tobacco consumption has actually declined in most developed countries. As for risk genes, which account for 25% of the probability of developing pancreatic cancer, their frequency in the Western population has, by definition, remained unchanged. “There is something, that’s for sure. But what, we don’t know,” regrets Catherine Hill, epidemiologist at Gustave-Roussy.
No statistical artifacts
Population growth and ageing, the launch of screening campaigns or the creation of better registers can sometimes artificially inflate official figures. But in this case, these statistical artefacts have been ruled out. “The increase is constant, it has been maintained over time and in many countries. It therefore suggests more of an increasingly high exposure to a carcinogen. But which one?” asks haematologist Eric Solary, chairman of the scientific council of the ARC foundation.
Many studies implicate type 2 diabetes, the type that develops due to a diet that is too sugary and too fatty. Its rise is parallel to that of pancreatic cancer, as shown in particular by a cross-analysis between figures from the Globocan initiative of the International Agency for Research on Cancer and health data from the WHO, published in 2021 in the journal Gastroenterology. Enough to make him one of the prime suspects.
Diabetes, cause or consequence?
In fact, the risk of developing pancreatic cancer is between 1.5 and 2.4 times greater in diabetics, according to a literature review published in Nature Reviews Gastroenterology & Hepatology, in 2021 still. But the reverse is also true: many people with pancreatic cancer subsequently develop diabetes. The organ is the main source of insulin and other digestive hormones. It is therefore impossible to say whether diabetes is a cause or a consequence of pancreatic cancer, or whether the similar evolution of the two pathologies is simply a correlation, with no proven link. Especially since many other risk factors also seem to be involved in the increase in the number of tumors. This is the difficulty that scientists face: there is no shortage of hypotheses, in fact there are too many.
Obesity may also be involved. In 2021, a study of a US cohort of over 160,000 people showed that overweight people had a 1.72 times greater risk of developing pancreatic cancer. Published in the Journal of American Medical Association (JAMA), these figures have since been confirmed. A deteriorated microbiota would also be associated with an additional risk. This is what is shown, among other things, by a meta-analysis published in 2017 in Annals of Oncology. But here the association is more tenuous.
A pet peeve: fat
In reality, scientists are struggling to find what damages the pancreatic system to the point of giving rise to a tumor. Do the factors mentioned act on the pancreas directly or on the immune system that protects it? Is there a direct effect on cancer, or are these simple statistical correlations? Professor Vinciane Rebours, coordinator of the National Reference Center for Rare Pancreatic Diseases at Beaujon Hospital in Clichy, readily admits that she cannot decide.
But the researcher, at the forefront in the field, still has her pet peeve: fat, especially when it is present in too great a quantity. “In my opinion, it is one of the most important risk vectors.” Normally stored under the skin, excess fat can accumulate around the abdominal organs and end up infiltrating the pancreatic cells. When such a build-up occurs, the probability of precancerous lesions occurring is much higher. This is what a study published in 2015 in the scientific journal Clinical Cancer Researchand signed by the scientist.
Other food substances have also been talked about without their role being confirmed. This is the case of red meat for example, classified as a probable carcinogen by the International Agency for Research on Cancer (IARC) in 2015, but whose harmful effects have mainly been observed on the intestine. Or alcohol – but its consumption is decreasing in the West, and its consequences on the pancreas are not very well demonstrated. Conversely, associations seem to indicate a protective effect of an allergic terrain, perhaps linked to the more active immune system of the individuals concerned. A diet rich in fruits and vegetables also seems beneficial.
Ultra-processed and “pro-inflammatory” foods
All these phenomena have a common denominator: the major changes in Western lifestyles and the emergence of ultra-processed food in the 1980s. With its recomposed dishes, this led to the absorption of fat, sugar and additives in much greater quantities than in the past. At the same time, the advent of office jobs, “tertiary”, has encouraged a sedentary lifestyle. “These are all behaviors that contribute to over-inflammation of the body and in particular of the pancreas”, emphasizes Vinciane Rebours.
However, inflammation is itself a risk factor. Patients with pancreatitis (an inflammation of the pancreas) are more often affected by pancreatic cancer than the rest of the population. Several analyses published in European Journal of Epidemiology in 2020 And 2022 have also shown that lifestyle (diet, alcohol consumption, sedentary lifestyle, body mass) and more specifically diet”proinflammatory” increase the risk of developing these tumors. These factors appear to be even more important than smoking.
To obtain these results, the researchers analyzed the health data of 400,000 Europeans, as part of theEuropean Prospective Investigation into Cancer and Nutrition (Epic). An unprecedented initiative that specialists would like to see multiplied in the years to come. “When the causes are too intertwined, or the cases are too few in number, science can only advance with the help of a comparative international perspective,” argues Eric Solary of the ARC foundation.
Doubts about pesticides
Often singled out, environmental pollutants could also play a role. The toxicity of pesticides or heavy metals in high doses is no longer in doubt. But most of the time, these substances end up in the body in quantities that are insufficient to observe clear effects. “Further work is needed to understand the role of environmental exposure,” concludes the literature review of Nature Reviews Gastroenterology & Hepatology which is a landmark on the subject.
In the case of pollutants, scientists come up against a methodological wall. There are many substances and they change often. In the absence of systematic screening of large population samples, it is impossible to obtain convincing results. “This does not mean that we should not continue research efforts, because there is a real question mark here, particularly regarding a possible cocktail effect,” points out Eric Solary.
A French project, called ecoPESTIPAC, could provide more information. Led by the Reims University Hospital in collaboration with Imperial College London, this work identifies the locations in France where pancreatic cancers are most common. They then compare them to agricultural activity. Initial results were published in March 2024, in Journal of Epidemiology and Population Healthbut they turn out to be disappointing. The two maps do not really overlap. They are very numerous in Paris and in the Bouches-du-Rhône for example, whereas in Brittany, a land of livestock and culture, there are very few.
Perhaps researchers will one day be able to dissect the exact role and effects of each risk factor. In the meantime, some scientists seem to have managed to get around the problem. A study based on data from the Danish Health Insurance recently caused a stir. It shows that with careful monitoring of health indicators, it is possible to “predict” the risk of developing pancreatic cancer. To obtain such results, Danish scientists gave artificial intelligence (AI) the health journeys of people who had been diagnosed with a tumor. Their conditions (diabetes, jaundice, gallstones, anemia, hypercholesterolemia), but also the frequency with which they visited the doctor and the content of their prescriptions were analyzed. Still in development, these tools could help identify risky “medical trajectories” and motivate early screening, believe the authors of the study, published in Nature Medicine in 2023. With the hope of being able to identify patients early enough to increase their chances of survival.
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