Obesity is the key that opens Pandora's box in dozens of diseases. The excessive accumulation of fat in the body is a risk factor that predisposes to a very disparate amalgam of ailments, the gateway to pathologies such as diabetes, heart disease, some neurological problems, mental health disorders or cancer. But not all excess adiposity impacts in the same way. An international investigation, published this Friday in
Science Advances
refines this reading of the impact of obesity on colorectal cancer and identifies, specifically, two body shapes that are associated with a greater risk of this type of tumor: of the four subtypes of adiposity described, people with generalized obesity and those Tall individuals with excess fat specifically concentrated in the abdominal area are more at risk of developing these tumors.
Colorectal cancer is the third most common tumor and the second cause of death related to this disease in the world, according to the World Health Organization (WHO): it is estimated that in 2020 there were almost two million new cases and 930,000 deaths a year. cause of this ailment. Apart from age, obesity is, along with other lifestyle habits such as smoking or alcohol consumption, one of the main risk factors. Overweight and obese people—who identify themselves with a body mass index (BMI) above 25 or 30, respectively—are more likely to develop these types of tumors, and the scientific community is now focused on defining as closely as possible. possible precision of those risk profiles. "Now, what is used as an anthropometric marker of health is the BMI and, although it works very well and is easy to calculate, it also presents some limitations: for example, with the BMI we can have individuals with a lot of weight, either because they have a accumulation of very high adiposity or because they are people who have very great muscle development. And this, metabolically, is very different and may or may not lead to disease through different molecular pathways. That is why now we are trying to develop new anthropometric indices that help us characterize this in a more global way,” explains Laia Peruchet-Noray, first author of the study and researcher at the International Agency for Research on Cancer (IARC). English).
Previous research by his team had already identified body shape phenotypes that were associated with a higher risk of suffering from up to 17 different tumors. And now, in another new study, they delve into the context of colorectal cancer: “That obesity is associated with colorectal cancer is something that is already widely assumed in science. What we wanted to do is try to find out if the different subtypes of adiposity were associated in different ways with colorectal cancer,” says the researcher.
The scientists characterized the participants—they used a cohort of nearly 330,0000 UK Biobank participants (3,728 of them with colorectal cancer)—according to four body patterns, based on six different anthropometric indices (BMI, weight, and head circumference). waist and hip, among others). “In the end, we obtain four different body shapes that are independent, but complementary to each other,” says Peruchet-Noray.
That is, four numbered body shapes are established—1, 2, 3 and 4—and each person is assigned a value based on their similarity to each of them. And depending on this value, “if it is higher or lower, your risk of colorectal cancer will change,” explains the researcher. The results revealed that form number 1, which characterizes individuals who accumulate adiposity more globally in the body, was associated with colorectal cancer. This same link was seen in phenotype 3, which describes tall people with abdominal fat. “Phetype 2, for example, which are tall individuals who do not accumulate adiposity in general, seems not to be associated with colorectal cancer. And, phenotype 4 would be more athletic people, because they have a high weight, but not so much abdominal adiposity; and we theorize that their weight comes from muscle and not so much from the accumulation of adipose tissue,” the scientist specifies.
The researchers clarify that all their findings are framed in an association, not causality. That is, it does not mean that all people with phenotypes 1 and 3 will develop cancer. “It must be taken into account that the general population has a baseline risk of a disease, which is normally the prevalence: the prevalence that we find of a disease in a population is the basic risk that any individual has and in the case of cancer, Even though they are scandalous diseases, the general risk is low,” contextualizes Robert Carreras, co-author of the study and scientist at the Doctor Josep Biomedical Research Institute of Girona. And he continues: “We have found, when we do these association studies where we observe relative risks greater than one, that the first phenotype of general obesity has a relative risk of 1.13. This means that a person who has high values of this parameter has a 13% greater probability than the baseline, but multiplying the baseline risk by 1.13 does not mean that, suddenly, a certain predisposition changes to a determination. One thing is association and predisposition and another is determination.” In the case of phenotype 3, the added risk is 9%.
But Peruchet-Noray insists that “not all people who have a high body shape value of 1 or 3 are going to develop colorectal cancer.” “What happens is that this is like a lottery and then, the more numbers you buy, the more likely it is that you will get it and having a high value of body shape number 1 or 3 means having bought some of the tickets. There are other risk factors, some known and others that we are still investigating, that give you a greater chance of developing the disease,” she emphasizes.
The research also characterized, at a genetic level, the four phenotypes and found that the origin of this adiposity is different depending on body shape. The molecular pathways that operate in phenotype 1 are different from those responsible in body shape 3. Carreras admits that they still do not know which pathways are activated to direct each of the phenotypes with the highest risk of ending up developing cancer, but they have delved deeper into “how these phenotypes are generated.” Body shape 1, which describes generalized obesity, “is generated by genetic expression activity in the brain, from neuronal tissue.” And from there, scientists interpret that this excessive accumulation of fat is associated with behavior, "both diet, food addiction, and anxiety, satiety, alcohol...". In the case of body shape 3, however, the key is not in the neuronal tissue, but in the adipose tissue. “We theorize that what happens is more at the metabolic level and not so much at the behavioral level,” explains Peruchet-Noray.
Different preventive approaches
These differential findings in genetic expression invite us to rethink preventive approaches in each case, says the researcher: “This opens the doors to a possible more personalized treatment. If you can know if the source of a person's obesity is, for example, due to behavior, because that person is more anxious, then to stop the growth of this adiposity, this individual should take more psychological measures. But this is not going to help obesity in a person who is more characterized by body shape number 3. In the end, it helps us to be more assertive with the preventive strategy for each individual.” Carreras goes one step further: “In future studies, if we know which genes are overexpressed or underexpressed to determine one type or another of obesity, if we are able to hit the right buttons, we could, through some type of therapy , make a preventive approach to weight gain.”
Ramón Salazar, head of the Medical Oncology service at the Catalan Institute of Oncology of L'Hospitalet (ICO), admits that, from a clinical point of view, one tends to be “skeptical regarding epidemiological studies”, but this research, in who has not participated, “it has been done very well,” he says: “They have sophisticated the way of measuring an effect that almost no one doubts: that obesity increases the risk of cancer. “They have identified two types of anthropomorphic obesity where there is an increase in colon cancer and they validate it through a genetic study,” he points out.
The oncologist admits that these specific findings will not have short-term implications in clinical practice, but “they do add another point of evidence to the hypothesis that the distribution of body fat can increase the risk of cancer due to a metabolic imbalance in the fabrics.” However, Salazar remembers that there is an important point of “randomness” in the development of cancer. “There are uncontrollable causes that explain up to 50% of tumors. The genetic lottery. Bad luck".