The link between cancer and fat explained

Colorectal cancer cells under the microscope. Photo / National Cancer Institute, Unsplash

Being overweight doesn't mean you'll automatically develop cancer, but from having a "spare tyre" to being "apple-shaped", carrying excess fat is associated with an increased risk of 13 forms of cancer. More than 1 in 20 cancer cases in the UK are linked to obesity, and this week, two new research studies have shed further light on the dangers.

Every year around 11,900 men in the UK die from prostate cancer – now epidemiologists at the University of Oxford have linked obesity to the disease for the first time. Using data from the UK Biobank study, they found that in overweight men, every additional four inches on their waistline increased their risk of dying from prostate cancer by 7 per cent.

Meanwhile, a separate paper from the University of Glasgow has found that women carrying lifelong excess weight around the stomach are twice as likely to develop womb cancer.

Such statistics are particularly troubling in the context of the UK's accelerating obesity epidemic, which has been predicted to result in around 670,000 new cases of cancer over the next two decades. But the connection between obesity and cancer is not present for all forms of the disease.

To date, the International Agency for Research on Cancer has linked 13 cancers to excess weight, including cancers of the gallbladder, stomach, liver, pancreas, kidney, ovaries, uterus, colon and rectum, as well as post-menopausal breast cancer.

"The problem with excessive visceral fat is that it affects certain processes in your body," says Dr Karen Basen-Engquist, a professor of behavioural science and director of the Center for Energy Balance in Cancer Prevention and Survivorship at the University of Texas MD Anderson Cancer Centre.

"This includes how your body manages hormones, like insulin and oestrogen. All of this can lead to an increased cancer risk by affecting how and when cells divide and die."

Epidemiologists at the University of Oxford have linked obesity to prostate cancer for the first time. Photo / Towfiqu Barbhuiya, Unsplash

The timing of weight gain also matters. For example, women who progressively gain weight from puberty to adulthood, and specifically in the third decade of life, should be considered at a higher risk for developing breast cancer.

The link between weight and disease is not necessarily definitive, though. While being overweight increases your odds of getting cancer, it may not always be a direct cause. Obese individuals may have other lifestyle factors that contribute towards them developing the disease.

"There could be confounding factors," explains Dr Dipender Gill, a researcher at Imperial College London. "For example, smoking may affect body weight, and smoking may also affect risk of cancer. They may also exercise less or have higher cholesterol."

Given mounting evidence linking obesity to particular cancers, scientists have been attempting to figure out the precise role that excess body fat plays in increasing the risk of the disease.

Inflammation

One of the major underpinning factors behind a third of all cancers is inflammation. Overweight people tend to carry more visceral fat – the body fat surrounding internal organs – that can slowly initiate chronic inflammation. This happens because visceral fat cells are very large, meaning there is not enough room for oxygen and this low oxygen environment triggers inflammatory processes.

"As we get heavier, the fat cells in our bodies get squeezed," notes Dr Michelle Harvie, a cancer researcher at the NIHR Manchester Biomedical Research Centre. "This low-grade inflammation running through the body damages healthy tissue, and damaged cells are the ones that become cancerous."

Harvie explains that while cell damage occurs naturally throughout our lives, the inflammatory environment created by obesity results in the body's normal repair mechanism not working as efficiently, increasing the chances of damaged cells developing into tumours.

Hormones

Being overweight can also disrupt your hormonal processes, thought to be one of the reasons why it plays a major role in womb cancer, ovarian cancer, postmenopausal breast cancer, and possibly even prostate and kidney cancer.

Extra fat doesn't just sit there, it is active, sending out signals to the rest of your body. These signals can tell cells to divide more often, which can lead to cancer.

"It is responsible for activating and metabolising a range of hormones, as well as itself producing hormones," says Gill. "It's that effect in particular that can have implications for cancer development and progression."

After women go through the menopause, the body stops deriving the hormone oestrogen from the ovaries and instead takes it from body fat. As a result, post-menopausal women who are overweight have far higher levels of oestrogen. This becomes a risk for certain cancers as it causes increased cell production.

The chronic inflammation caused by obesity can lead to the development of insulin resistance, whereby the body does not properly respond to the hormone insulin. This induces a destructive cycle where the body produces excess insulin, which then leads to more cells being produced, and in turn heightens the risk of developing cancer.

Microbiome

Around 11 per cent of colorectal cancer cases in Europe have been attributed to obesity, with the risk factor being particularly notable in men.

Professor Sir Mel Greaves, founding director of the Centre for Evolution and Cancer at the Institute of Cancer Research, suspects part of the reason why overweight people are at a greater risk of colorectal and other cancers is a consequence of a disturbed gut microbiome.

"The microbiome is incredibly complicated," he points out. "There are hundreds of species of bacteria, and viruses and fungi, and the bacterial species in particular have an extraordinary regulatory control over our metabolism, and our immune systems. We know that the microbiome can be profoundly affected by diet, and eating the wrong things."

Studies have previously shown that colorectal cancer patients have an overabundance of bacterial species that are linked to chronic inflammation, as well as a reduction of bacteria which produce a chemical called butyrate. Insufficient butyrate has been linked with abnormal cell behaviour.

Treatment

Being overweight can also reduce the chances of doctors being able to treat certain cancers.

According to Ghulam Nabi, a clinical professor at the University of Dundee, if a patient is very obese, it makes it harder to precisely target a tumour with radiotherapy.

"The rays might not reach the intended origin," he says. "Similarly with surgery. The fat might cause problems with distinguishing where the cancer is."

There is also a theory that obese patients may be more likely to develop aggressive or metastatic cancers. "When a tumour starts, it grows to an extent and then it finds its nutrition is compromised," explains Nabi. "So it starts cross-talking with neighbouring cells, and if those are fat cells, then it can use them to promote its continued growth."

Losing weight can reduce risk

But the good news is that research also shows that losing weight at any age can subsequently reduce your risk – and the sooner you do so, the better.

University of Oxford scientists discovered that reducing the average male body mass index (BMI) by five points – equivalent to 2.5 stone (15.8kg) – would prevent 1300 prostate cancer deaths per year. Harvie has also found in the past that weight loss can reduce the risk of post-menopausal breast cancer by 25 to 40 per cent.

She is at pains to point out that even people who are born with a hereditary trait which predisposes them towards a certain type of cancer can still greatly reduce their chances of ever developing it by keeping tabs on their weight.

"So many health problems are associated with being overweight," she says. "And cancer is another, and one where people can potentially modify their risk, even people that have a genetic predisposition."