Being overweight or obese increases the risk of developing several types of cancer, although the reason is not entirely clear. These conditions may not be the direct cause of this increase, however, various studies suggest that the cause may be in the alterations that these conditions cause in the body, or in the changes resulting from these physical conditions. Understanding the relationship between obesity, overweight and cancer is essential.
Understanding this relationship is essential, since, according to the data from the European Health Survey in Spain 202016.5 percent of men over 18 years of age and 15.5 percent of women suffer from obesity in our country. In addition, overweight affects 44.9 percent of men and 30.6 percent of women. For this reason, different research groups at the Spanish National Cancer Research Centre (CNIO) are working to understand the relationship between these pathologies.
Liver and colon cancer
“Epidemiological studies that show a very high relationship, especially with liver and colon cancer, although also with others, but with less statistical evidence; They began in 2010. Shortly after, the phenomenon was studied in animal models and it was quickly seen that those with a high-fat diet showed a propensity for liver cancer, a relationship that was also seen later with other types of tumors,” he points out. Guadalupe Sabio director of the Interorgan Interaction Group in Metabolic Diseases at the CNIO. One of the tissues that is most damaged by obesity is adipose tissue, and in this sense, Sabio’s group discovered that if a type of highly active protein is removed from adipose tissue in obese people, the risk of cancer is reduced. “We discovered that when we removed 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,” adds the researcher.
Sabio’s team began to analyze these protein kinases by differentiating between “obese and thin people and, something that had not been done before, between women and men,” which allowed them to discover that this pathway is less active in women than in men. “This was a very significant finding, because Men are four times more likely than women to develop a liver tumor“, explains Sabio.
Now, the group is investigating how fat affects other types of cancer, such as breast cancer, and continues looking for blood biomarkers fat related that can indicate whether a person is at greater risk of liver cancer.
Pancreatic cancer, obesity and the microbiome
On the other hand, the researcher Núria Malats, leads the team at the CNIO Epidemiology and Molecular Genetics Group, has led a large international study, PanGenEU, dedicated to investigating the factors associated with the risk of pancreatic cancer. The objective 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, which is why 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 not yet understood. “We believe that the role of obesity is much more complex and we think that there are other related factors,” he adds. Along these lines, Malats’ group had already shown that Long-standing 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 the previous conditions that lead to both diabetes and obesity could be the cause of the increased risk of pancreatic cancer,” says the specialist.
These preconditions could lead to a mild, chronic inflammation of the pancreas, which would induce diabetes and obesity and, finally, 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. Now, this is a line of research that is being explored with the CNIO Epithelial Carcinogenesis Group, led by Paco X. Real.
Metastasis
Hector Peinado, head of the Microenvironment and Metastasis Group at CNIOinvestigates the relationship between obesity or overweight and metastasis, the process by which a primary tumor reproduces in other organs, spreading throughout the body. Little is known about this point, but “it seems clear that obesity influences the spread of cancer, but research had not focused, until now, on explaining molecularly why this happens,” Peinado points out. That is what she began to investigate in 2015. “We started with melanoma and observed that in obese mice the cancer cells metastasized better. Then we moved on to breast cancer, a tumor whose risk is more 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,” she adds.
Based on these results, the group established a hypothesis. “We believe that obesity affects the organs to which cancer metastasizes. On the one hand, obesity increases what is known as vascular permeability. We have observed that in the organs where there are metastases this vascular permeability also increases,” says the researcher. “Another change caused by obesity is the increase in platelet activity, and we see the same thing in our mouse models in organs with metastases. It seems that the tumor cell takes advantage of these two circumstances to nest and form metastases,” he says.
Peinado is now focusing on humans. “We are collaborating with Miguel Quintela’s group, from the CNIO Breast Cancer Clinical Research Unit, to try to extrapolate our observations to patients. Our hypothesis is that obesity has a systemic influence on metastasis, and we are looking for ways to control or reverse this process,” he says.
Closer relationship
The National Cancer Institute (NIH) identifies 13 types of cancer whose risk increases with obesity or overweight in varying proportions:
Likewise, experts highlight that each five-unit increase in Body Mass Index (BMI) increases the risk of breast cancer after menopause by 1.2 times and the risk of ovarian cancer by 1.1 times.
In this line, one of the therapeutic strategies that are being addressed is based on diet. The success of this strategy has been proven in mouse models. “We are exploring different therapeutic approaches in our mouse models. For example, switching from a high-fat diet to a normal diet, we observed positive results. Extrapolating these findings to human patients, this would imply adopting healthier eating habits, such as a balanced diet instead of consuming saturated fats and processed foods,” explains Peinado, who also points out that “our data suggests that a change in diet could reduce ability of tumor cells to metastasize. “In addition, we are investigating the use of platelet aggregation inhibitors, which also show potential to reduce the formation of metastasis.”
You may also like…