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Obesity and cancer

Obesity linked to increase in womb cancer cases

How exactly does fat increase our risk of cancer?

Rising levels of obesity among UK women have helped fuel a 54 per cent increase in womb cancer rates over the last two decades, according to Cancer Research UK’s latest statistics. In the early 1990s, around 19 women in every 100,000 developed the disease. That figure has now climbed to 29 women in every 100,000 – with obesity being the most likely culprit. Approximately 9,000 women are diagnosed with womb (uterine) cancer every year in the UK, and around 2,000 women die from the disease. Twenty years ago, there were around 4,800 new cases of womb cancer each year with around 1,500 deaths.

“It’s worrying that womb cancer cases are going up so sharply,” said Professor Jonathan Ledermann, director of the Cancer Research UK and UCL Cancer Trials Centre. “We don’t know all the reasons why. But we do know that about a third of cases are linked to being overweight so it’s no surprise to see the increases in womb cancer cases echo rising obesity levels.”

The science behind how extra weight can cause cancer is not completely clear. But there is evidence that extra fat in the body can raise cancer risk by producing hormones and growth factors that encourage cells to divide. A lack of exercise and taking HRT (hormone replacement therapy) are also risk factors – but are linked to fewer cases of womb cancer than obesity. A woman’s age and genetic make-up can also affect her risk.

“The good news is that thanks to research and improved treatments survival has improved,” added Ledermann. “In the 1970s, almost six in ten women diagnosed with the disease survived for at least ten years. Now almost eight in ten women survive. But we need more research to understand the biology of the disease better and to know more about how it is caused so that we can improve the treatment of these women as well as preventing more cases.”

Despite efforts to raise the profile of the link, public awareness remains stubbornly low, only around one in ten people name being overweight as a factor when asked what things they think affect a person’s chance of developing cancer. With worldwide obesity rates increasing, and the condition already linked to nearly 500,000 cancer cases worldwide every year, the number of cases is likely to increase.

According to recent reports, public health experts predict that in the US obesity will soon overtake tobacco as the leading preventable cause of cancer, and the UK might one day follow suit.

How exactly does fat increase our risk of cancer?

According to Cancer research UK, while there are several plausible explanations, it’s an answer that researchers are still working on, although there are currently three theories (Figure 1). Fat (also known as adipose tissue) has two main roles in the body. It primarily exists to store calories in the form of chemicals called lipids, which when food was scarce would serve as a back-up energy store to keep us going. However, today many people consume more calories than they use up, leading to more of us becoming overweight or obese.

Fat also has a secondary function – it’s essentially a huge gland, sending out a constant stream of biological information and instructions that affect the rest of your body. This helps control processes like growth, metabolism and reproductive cycles.

Because of their ability to turn biological processes on and off, the signals produced by fat have a darker side when it comes to cancer. This is especially true when people become overweight or obese – the point at which excess fat has a negative impact on health. Here are the three leading theories about how excess fat might lead to cancer, and the scientific evidence behind each one.

(Credit: Graphic by Alice Cotelli, information designer at Cancer Research UK, click here to see the original image)

The oestrogen connection

According to Cancer research UK, one of the strongest links between obesity and cancer is an increased risk of breast and womb cancers in women who are overweight or obese after the menopause, and this relates to higher oestrogen levels.

In pre-menopausal women, the ovaries are the main oestrogen-producing cells. However, fat cells can make oestrogen too and, after the menopause, when the ovaries stop working, fat becomes the chief source of the hormone. And there is solid evidence showing that being obese leads to higher oestrogen levels in women after the menopause.

Professor Martin Wiseman, a leading expert on diet, weight and cancer from the World Cancer Research Fund, claims that oestrogen made by fat cells is a leading culprit in postmenopausal breast and womb cancer.

“The evidence that oestrogen plays a central role in some cancers is black and white. Oestrogen makes certain cells – like breast and womb cells – divide, so too much oestrogen can encourage cells to keep dividing when they shouldn’t be. And uncontrolled cell division is fundamentally what cancer is,” he explained. “Large studies of women have shown a direct relationship between obesity, high oestrogen levels and breast and womb cancers and understanding this relationship has been critical in developing effective treatments – like tamoxifen and aromatase inhibitors – that work by cutting off oestrogen. Furthermore, if women at high risk of breast cancer are given oestrogen-blocking treatments, fewer go on to develop the disease. Cutting off oestrogen can stop breast cancer developing.”

While the link to women’s cancers is stronger, there’s also data suggesting that obesity-related changes in sex hormones can play a role in men’s cancers too. There’s evidence that, while rare, breast cancer in men is linked to increased oestrogen caused by excess body fat. Obesity is also linked to higher rates of aggressive prostate cancer, but it’s unclear if changes in oestrogen from fat cells play a role, or whether it could be down to changes in testosterone, the male sex hormone.

Metabolic chaos

The metabolic processes are complicated and tightly controlled, relying on a finely tuned web of information flowing between cells and organs. However, the chemical signals produced by fat cells means that obesity can cause a major upset to this balance, and this is thought to be another way it makes cancer more likely.

One key hormone that acts as a master-controller of metabolism is insulin. But insulin’s instructions can be overridden by chemicals in blood known as free fatty acids – the levels of which can be affected by eating a fatty meal, for example. This flips a switch in liver and muscles, telling them to use this fat as fuel instead of glucose.

But it’s not just eating fatty food that increases free fatty acid levels in blood. Body fat, especially around the abdomen, can also release them – it’s the body’s way of using up fat stores. Excess body fat can lead to rising  levels of free fatty acids, leaving cells increasingly resistant to the effects of insulin and unable to take up glucose properly.

“This can cause all kinds of problems”, said Wiseman. “Cells become resistant to insulin, so the pancreas makes more to try and compensate and bring blood glucose levels back down. Higher amounts of insulin have a knock-on effect of re-programming the levels of growth factors available to cells, and both insulin and these growth factors can become a danger when it comes to cancer. Growth factors are a green light signal for cells to divide”.

There’s also substantial laboratory evidence of a link: lots of data showing that as cancer cells react to both insulin and insulin-related growth factors, they become harder to kill, and divide more quickly.

Taken together, the evidence that disturbances in metabolism lead to cancers is compelling. The big question is the degree to which it plays a role in the increased rates of cancer in obese people – and studies are on-going to find this out.

Inflammation

As people become obese, and more fat cells build up in their tissues, specialised immune cells (called macrophages) are called to the scene, possibly to clear up dead and dying fat cells. But as macrophages carry out their clean up job, they also release a potent cocktail of chemicals called cytokines that summon other cells to help them out. The number of macrophages in obese fatty tissue can be substantial – they can account for as many as four in ten cells.

This ultimately creates a condition called chronic inflammation – and this is another way that obesity is thought to fuel the development of cancer. And it’s been shown that obese people tend to have higher levels of inflammatory cytokines in their blood.

The evidence that inflammation is linked to cancer is damning. Many chronic inflammatory diseases (such as pancreatitis and Crohn’s disease) can increase a person’s risk of cancer. And cancers caused by infections are also characterised by chronic inflammation.

“The result of inflammation is a cocktail of signals that tell cells to divide, because after injury you need new cells for healing to occur,” said Wiseman. “But the signals encouraging cell growth for healing can also support cancer cells dividing. In fact if we look at the genes that are turned on and off in inflamed tissue, it’s very similar to genetic changes we see in cancer cells. There’s strong evidence that aspirin, a drug that reduces inflammation, prevents bowel cancer, or other anti-inflammatory drugs may also be beneficial when it comes to treating, and possibly preventing, other types of cancer.”

There’s not a shadow of doubt that obesity is linked to cancer, but unravelling the biological reasons why is proving complicated. Being obese affects lots of different aspects of our physiology – hormones, growth signals, and inflammation. It also affects different people in different ways; for example, not everyone who is obese will have abnormal metabolism or chronic inflammation.

To make matters more complicated still, oestrogen, insulin, and inflammation are a convoluted tapestry of interwoven threads. None of them in isolation directly causes cancer, but in obesity they knit together to form a lethal fabric – dampening the delicate systems that balance our bodies with disastrous consequences.

And while it’s not simple to understand how the threads weave into the overall picture, researchers know that there’s potentially an opportunity to treat, or even prevent, cancer by developing drugs that override signals made by fat cells. For example, both metformin (a diabetes drug that affects insulin levels) and aspirin (which dampens down inflammation) are under investigation as possible anti-cancer drugs.

“It’s concerning that more women are developing womb cancer, but it’s important that they are informed about ways to reduce their risk of the disease,” said Dr Julie Sharp, head of health information at Cancer Research UK. “Obesity is linked to ten different types of cancer, including womb cancer, and is the single biggest preventable cause of the disease after smoking. While there are no guarantees against cancer, keeping a healthy weight can help you stack the odds in your favour and has lots of other benefits too.”

This article was sourced from information provided by the Cancer Research UK website. For more information, please click here

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