21% of Spanish adults suffer from obesity (18% of the child and youth population) and 40% are overweight, according to the Spanish Society for the Study of Obesity (Seedo). And, if nothing is done, by 2034 there will be, according to the “World Obesity Atlas”, 37% of the adult population with obesity.
Being obese or overweight increases the risk of developing several types of cancer, but the reason is not clear. In fact, they may not even be a direct cause of this increase.
It is a disease of the adipose tissue itself, which, when it increases with weight gain, is damaged and this damage affects practically all the organs of the body. Some research suggests that the origin of obesity is in the alterations that it causes, or perhaps in the changes in the organism derived from these physical conditions.
Three teams of researchers from the Spanish National Cancer Research Centre (CNIO) are seeking to understand the relationship between obesity, overweight and cancer.
Guadalupe Sabio heads the CNIO Organ Interaction in Metabolic Diseases Group, which studies the relationship between cancer and obesity: “Epidemiological studies showing a very high relationship, especially with liver and colon cancer – and with other cancers as well, but with less statistical evidence – began in 2010. Shortly afterwards, the phenomenon was studied in animal models and it was quickly seen that those with a high-fat diet were more prone to liver cancer, a relationship that was later also seen with other types of tumours.”
One of the tissues that is most damaged by obesity is adipose tissue – the fat present in the usual ‘love handles’. Sabio’s group found a certain type of very active proteins in obese people. If they are removed of adipose tissue, the risk of cancer is reduced.
“We discovered that when we eliminated them from the adipose tissue of animals, they had a lower risk of developing liver cancer. From there we began to study how these proteins are in people,” explains Sabio in a CNIO statement.
The researcher began to analyze these protein kinases, differentiating between “obese and thin people and, something that had not been done before, between women and men.”
And what she and her team discovered was that Women have this pathway less active than men.. “This was a very significant piece of information, because Men are four times more likely than women to develop a liver tumor.“, says Sabio.
Following this discovery, this group is now investigating how fat affects other types of cancer, such as breast cancer, and is continuing to search for blood biomarkers related to fat that can tell us whether a person is at higher risk of developing liver cancer.
Pancreatic cancer, obesity and the microbiome
Núria Malats, who heads the Epidemiology and Molecular Genetics Group at the CNIO, has led a large international study, PanGenEU, dedicated to investigating the factors associated with the risk of pancreatic cancer. The ultimate goal is to establish screening programs that allow early detection of the disease.
Pancreatic cancer is usually detected in advanced stages and usually causes death within a year after diagnosis, so it is crucial to advance early detection.
“Pancreatic cancer is one of the cancers most associated with obesity as a risk factor,” says Malats. But the relationship is still not understood: “We believe that the role of obesity is much more complex and we think that there are other related factors,” she adds.
Malats’ group had already shown that long-term type 2 diabetes is a risk factor for pancreatic cancer. “We believe that diabetes mediates the effect of obesity, and obesity mediates the effect of diabetes, and neither factor has a causal relationship with pancreatic cancer. “This suggests that pre-existing conditions that lead to both diabetes and obesity could be the cause of the increased risk of pancreatic cancer.”
Those preconditions could lead to mild, chronic inflammation of the pancreas, inducing diabetes and obesity and, eventually, pancreatic cancer. “The causes of this inflammation may be genetic or related to the microbiome, the community of microorganisms that live in our bodies,” says Malats. It is a line of research that is being explored with the CNIO Epithelial Carcinogenesis Group, directed by Paco X. Real.
Metastasis and obesity
Héctor Peinado, head of the Microenvironment and Metastasis Group at the CNIO, investigates the relationship between obesity or overweight and metastasis, the process by which a primary tumor reproduces in other organs, spreading throughout the body.
An aspect about which very little is still known. “It seems clear that obesity influences the spread of cancer, but research had not focused, until now, on molecularly explaining why this happens,” says Peinado.
This is what she began to investigate in 2015. “We started with melanoma, and we saw that in obese mice cancer cells metastasize better. Then we moved on to breast cancer, a tumor whose risk is more closely related to obesity than melanoma. In this case, too, we found that cancer cells metastasized better in obese mice. So we already had evidence in two types of cancer: melanoma and breast.”
With these data, the group established a hypothesis: “We believe that obesity affects the organs in which cancer metastasizes. On one side, Obesity increases what is known as vascular permeability. And we have seen that in The organs in which there is metastasis also increase vascular permeability” says the researcher.
“Another change that obesity causes is the increased platelet activityand we see the same thing in our mouse models, in organs with metastasis. It seems that The tumor cell takes advantage of these two circumstances to nest and form metastasis.”Add.
Peinado is now focusing on humans: “We are collaborating with Miguel Quintela’s group, from the Breast Cancer Clinical Research Unit at CNIO, to try to extrapolate our observations to patients. Our hypothesis is that obesity has a systemic influence on metastasis, and we are looking for a way to control or reverse it.”
Diet-changing strategies do work in mouse models: “We are testing therapeutic strategies in our mouse models. For example, changing from a high-fat diet to a normal diet. Extrapolated to a patient, this would mean eating healthier, eating a balanced diet instead of eating saturated fats and processed foods. The data suggest that a change in diet could reduce the ability of tumor cells to metastasize. And, on the other hand, we use platelet aggregation inhibitors that also reduce this ability for metastatic implantation,” explains Peinado.
Advancing knowledge of the relationship between obesity and overweight and cancer is essential in Oncology. According to the National Cancer Institute of the United States, between Between 2011 and 2015, there were 37,670 new cases of cancer in men and 74,690 in women that were related to excess body weight. In Spain there is no specific data.
Furthermore, between 2005 and 2014, most cancers associated with overweight and obesity increased by 7% in the United States, while cancers associated with other factors decreased by 13%.
There are thirteen types of cancer whose risk increases with obesity or being overweight. in varying proportions, according to the United States National Cancer Institute.
Thus, the risk of endometrium increases seven times in case of severe obesity and four times in case of both obesity and overweight. In the case of esophageal adenocarcinoma, severe obesity increases the risk of suffering from this tumor by 4.8 times, between 2.4 and 2.7 in the case of obesity and 1.5 if overweight.
Other tumors related to high weight gain are cancer of the gastric cardia, liver, kidney, multiple myeloma, meningioma, pancreas, colorectal, gallbladder, breast (they consider it two types depending on whether it occurs before or after menopause) and thyroid.
Specifically, being overweight and obese increases the risk of breast cancer before menopause by 0.8% and Each increase of 5 units in the Body Mass Index (BMI), which is the indicator with which obesity and overweight are measured, increases the risk of breast cancer after menopause by 1.2 times and the risk of breast cancer after menopause by 1.1 times. of ovarian cancer.