Two body shapes linked to higher risk of colon cancer | The science

Obesity is the key that opens Pandora’s box for dozens of diseases. Excessive accumulation of fat in the body is a risk factor that predisposes to a very diverse set of diseases, and is a gateway to pathologies such as diabetes, heart disease, certain neurological problems, mental disorders or cancer. But not all excess obesity is affected equally. An international investigation published this Friday in Science achievementsrefines this understanding of the impact of obesity on colorectal cancer and specifically identifies two body shapes that are associated with a higher risk of this tumor type: Of the four obesity subtypes described, people with generalized obesity and tall people with excess fat especially concentrated in the abdominal area, they are more susceptible risk of developing these tumors.

According to the World Health Organization (WHO), colorectal cancer is the third most common tumor and the second cause of disease-related deaths in the world, with an estimated nearly two million new cases and 930,000 deaths reported worldwide in 2020. the cause of this illness. Besides age, obesity, along with other lifestyle habits such as smoking or drinking alcohol, is a major risk factor. Overweight and obese people, who identify 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 determining the accuracy as closely as possible. these risk profiles. “BMI is now used as an anthropometric marker of health, and although it works very well and is easy to calculate, it also has some limitations: for example, with BMI we can have people who are overweight, either because they have accumulated very high amount of obesity, either because they have very well developed muscles. And that, from a metabolic standpoint, is very different and may or may not lead to disease through different molecular pathways. That’s why we are now trying to develop new anthropometric indices that will help us characterize this more globally,” explains Laia Perouche-Noray, first author of the study and researcher at the International Agency for Research on Cancer (IARC English). ).

His team’s previous research had already identified body shape phenotypes that were associated with a higher risk of developing 17 different tumors. And now, in another new study, they delve deeper into the context of colorectal cancer: “The fact that obesity is associated with colorectal cancer is already widely accepted in science. We wanted to try to find out whether different subtypes of obesity are associated with colorectal cancer differently,” says the researcher.

The scientists characterized the participants – they used a cohort of almost 330,000 UK Biobank participants (3,728 of them with colorectal cancer) – into four body models based on six different anthropometric measures (BMI, weight and head waist circumference). and hip, among other things). “We end up with four different body shapes, independent but complementary,” 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 resemblance to each of them. And depending on that value, “if it’s higher or lower, your risk of colorectal cancer will change,” the researcher explains. The results showed that form number 1, which characterizes people who accumulate obesity on a more global scale in the body, is associated with colorectal cancer. The same association was observed in phenotype 3, which describes tall people with abdominal fat. “For example, fetype 2, which is tall people who generally do not become obese, does not appear to be associated with colorectal cancer. And phenotype 4 is more athletic people because they have a lot of weight, but not as much abdominal obesity; and we assume that their weight is due to muscles, and not so much the accumulation of adipose tissue,” the scientist clarifies.

The researchers explain that all their findings are based on association, not causation. That is, this does not mean that all people with phenotypes 1 and 3 will develop cancer. “We must take into account that in the general population there is a baseline risk of disease, which is usually the prevalence: the prevalence that we find in a population is the basic risk that any individual has, and in the case of cancer, “Although these are scandalous diseases, the overall risk is small,” explains Robert Carreras, co-author of the study and researcher at the Dr. Josep Institute for Biomedical Research in Girona. And he continues: “When we do these association studies where we see a relative risk greater than one, we found 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 probability of 13% greater than the base level, but multiplying the base risk by 1.13 does not mean that a certain predisposition will suddenly change to determinism. Association and predisposition are one thing, determination is another.” In the case of phenotype 3, the additional risk is 9%.

But Perouche-Noray insists that “not all people who have a high body shape score of 1 or 3 will develop colorectal cancer.” “What happens is that it’s like a lottery: the more numbers you buy, the more likely you are to get it, and having a high body shape number of 1 or 3 means you bought multiple tickets. There are other risk factors, some of which are known and others we are still studying, that increase the likelihood of developing the disease,” he emphasizes.

The study also genetically characterized the four phenotypes and found that the cause of obesity differs depending on body shape. The molecular pathways that operate in phenotype 1 are different from those responsible for body shape 3. Carreras admits that they still don’t know which pathways are activated to direct each of the highest-risk phenotypes to eventually develop cancer , but they dug deeper. in “how these phenotypes are generated.” Body Shape 1, which describes generalized obesity, “is created by genetic expression activity in the brain, in neuronal tissue.” And from there, scientists interpret that this excessive fat accumulation is related to behavior, “both dieting, food addiction, and anxiety, satiety, alcohol…”. However, in the case of body shape 3, the key is not in the neuronal tissue, but in the adipose tissue. “We hypothesize that what’s happening is more at the metabolic level rather than at the behavioral level,” Perouche-Noray explains.

Various preventative approaches

These different results in genetic expression prompt us to rethink preventative approaches in each case, the researcher says: “This opens the door to possible more personalized treatments. If you can know whether the source of a person’s obesity is, for example, behavior because that person is more anxious, then to stop the increase in that obesity, that person should take additional psychological measures. But it won’t help eliminate obesity in someone who is more of a body shape 3. Ultimately, it will help us be more aggressive about prevention strategies for each individual.” Carreras goes even further: “In future research, if we know which genes are overexpressed or underexpressed in determining which types of obesity, if we can push the right buttons, we could, through some type of therapy, create a preventative approach to weight gain.” .

Ramon Salazar, head of the medical oncology service at the Catalan Institute of Oncology L’Hospitalet (ICO), admits that from a clinical point of view people tend to be “skeptical of epidemiological studies”, but this study, which was not involved, “was done very well” , he says: “They have developed a way to measure an effect that almost no one doubts: obesity increases the risk of cancer. “They identified two types of anthropomorphic obesity that are associated with an increased incidence of colon cancer, and confirmed this using genetic research,” he notes.

The oncologist acknowledges that these specific findings will not have short-term significance in clinical practice, but “they add further evidence to the hypothesis that body fat distribution may increase cancer risk due to metabolic imbalances in tissues.” ” However, Salazar remembers that there is an important aspect of “chance” in the development of cancer. “There are uncontrollable causes that explain up to 50% of tumors. Genetic lottery. Bad luck”.

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