One in five people who die of cancer are obese. Now researchers can tell us more about why.
Abundant fat substances make cancer cells more aggressive and more capable of forming tumours, according to a study conducted by researchers at the University of Bergen.
Researchers have long known that overweight and obese people are more likely to develop certain cancers, such as colorectal cancer, liver cancer and pancreatic cancer.
Until now, however, no one has known exactly why overweight people are more susceptible to these cancers.
A research team at the Department of Biomedicine at the University of Bergen has taken a closer look at the underlying mechanisms and made an important discovery. The study was recently published in the journal Nature Communications.
“The finding may be the start of developing more personalized cancer treatment for obese patients.
Researcher Nils Henrik Halberg at UiB
“The finding may be the start of developing more personalized cancer treatment for obese patients,” says researcher Nils Henrik Halberg, an associate professor at UiB.
Mouse trials and clinical trials
Cancer is caused by genetic changes in cells that then interfere with normal cell growth.
“Single cells with the potential for cancer are not in themselves dangerous. Most of us have some in our body all the time, but they’re cleared out by the body's immune system. Only when the cancer cells form tumours do they become dangerous,” Halberg says.
Together with his colleagues, Halberg has studied cancer cells in the laboratory, experimented with mice and done research on cancer tissue from patients to see whether cancer occurs and how aggressive it is.
Injecting cancer into obese mice
The research team started by researching breast cancer which is not hormone dependent. This is a form of cancer that overweight women are more prone to developing after menopause.
By exposing cancer cells to abundant lipids, they first observed what was happening in the laboratory. Lipids are fats that overweight people tend to have a lot of.
Then the researchers injected the cancer cells into lean and fat mice.
“We created an overweight environment for the cancer cells by fattening up some of the mice,” says Halberg.
Cancer cells forced to become more aggressive
The result was the same in the mice as in the lab dishes.
Cancer cells have ten times the chance of succeeding at forming cancerous tumours in mice in an overweight environment than in a less fat-rich environment, says Halberg.
“We found that cancer cells in lipid-rich environments become more aggressive and more easily form cancerous tumours,” says Halberg.
But more available nutrients are not what makes cancer cells multiply more easily in overweight people.
“This high-fat environment forces the cancer cells to change in order to survive,” he says.
The lipid-rich environment leads to selection pressure, which causes the cancer cells to change. Only those cells that are able to adapt to the high-fat environment survive. This happens through a form of epigenetics.
At the same time, these altered cancer cells – as an unfortunate consequence – become more dangerous and can form tumours more easily.
Found a certain protein
The researchers then looked for differences in the cancer cells that formed tumours, compared to those that did not.
They found a certain protein in the cancer cells that had changed and become more dangerous. Then they examined the tissue of about 90 cancer patients from a biobank.
“We found that the same protein was far more prevalent in patients who were overweight than in patients who were normal weight,” says Halberg.
Cancer treatment less effective for people with obesity
Cancer treatment also appears to work less well for this patient group.
“Overweight and obese people generally have a poorer cancer survival rate than normal weight individuals,” says Halberg.
Although the researchers found a ten-fold increased risk of developing cancerous tumours in overweight and obese mice, the risk is not quite as high in humans.
But Halberg emphasizes that the cancer cells in overweight people are different than in normal-weight people.
This may explain why different types of chemotherapy do not work equally well in all patients. Some respond positively to treatment, whereas others get better and then suddenly have a relapse.
"This finding may be the starting point for finding new and personalized treatments and medications for cancer patients who are overweight or obese", says the researcher.
Exciting and useful
Previous epidemiological research has been done on the link between obesity and breast cancer risk. But these studies have not been able to establish a definite causal relationship.
“It’s exciting and really useful to have more experimental data on this link,” says Therese Sørlie, a biologist at Oslo University Hospital.
She heads the Department of Cancer Genetics at Radiumhospitalet, OUS.
This research is also useful due to the increase in obesity in the population across large parts of the industrialized world, Sørlie says.
“In the longer term, we hope that increased insight into the mechanisms for how breast cancer develops will influence patient treatment,” says Sørlie.
Does it matter what part of your body is big?
During the experiments, the researchers found that the risk of tumour formation increased in proportion to increasing body mass index. The more overweight, the greater the risk.
“In the study we included both overweight mice and overweight people with BMIs between 25 and 30, and ones who were obese with BMIs over 30,” says Halberg.
When it comes to breast cancer, many women’s breasts get bigger with age. The breasts are often mostly large fat deposits,” says Halberg.
But in general, overweight and obese people have more lipids – or fatty acids – in the bloodstream, and cancer cells are fed through the blood supply.
For a number of other cancers where overweight and obesity increase the risk, internal belly fat is especially dangerous. Large waist circumference is also a risk factor for a number of other lifestyle diseases such as high blood pressure, type 2 diabetes and cardiovascular disease.
“Large fat stores on the thighs, buttocks and hips in women, on the other hand, aren’t that dangerous, but serve more as extra energy stores,” says Halberg.
Obesity is catching up with smoking as a cause of cancer
Smoking has long been the most important lifestyle factor that increases the risk of cancer. Now obesity is catching up, says Halberg.
Lifestyle factors are habits that you can try to change yourself to lower your risk of disease.
Fewer and fewer people are smoking in the world, and more are becoming overweight and obese. So the curves on the graph will soon cross each other, according to the researcher.
About five percent of cancer cases are estimated to be due to obesity, and between 15 and 20 per cent of cancer deaths are due to obesity.
The WHO estimates that as many as 500 000 new annual cases of cancer worldwide are due to overweight and obesity.
However, being too thin is not good either. Some cancers are more common among people who are underweight, such as cancers of the oral cavity, oesophagus, stomach and lungs.
Reference:
X. Lui et al: C / EBPB-dependent adaptation to palmitic acid promotes tumour formation in hormone receptor negative breast cancer. Nature Communications, 2021.
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Read the Norwegian version of this article at forskning.no
