We have known for a long time that losing weight is healthy for overweight or obese people. Articles published over 25 years ago, like the 1991 Scientific American article “Gaining On Fat,” made it clear that obesity increases risk of heart disease, osteoarthritis, and high blood pressure. The association between obesity and these risk factors is common knowledge today, especially now that obesity affects 35.7% of the population according to the National Institutes of Health.
But many of us do not associate obesity with cancer.
Recently, though, scientists have found evidence that obesity causes cancer. This information is not as well known; in fact, according to the American Institute of Cancer Research, less than half of us realize that obesity and cancer are linked. Up until the 1990s, even scientists did not think they were related. They thought that fat tissue did not have much purpose besides storing and releasing fatty acids. It is obvious that obese people have excess body fat, but scientists did not think this extra tissue had any significant function. Scientists now know that this tissue is in fact highly active in hormone regulation and sugar balance, both of which regulate cell division and can cause cancer. According to the American Institute of Cancer Research, around 15% of cancers, or 85,000 cases of cancer a year, are caused by excess fat.
While obesity contributes to many types of cancer, obesity highly influences the risk of postmenopausal breast cancer. Postmenopausal obese women are more susceptible to breast cancer due to their hormone levels, and they are susceptible to cancer in general because of their weight. In all our bodies, fat tissue produces estrogen, a hormone that older women ordinarily stop producing after menopause. In obese postmenopausal women, estrogen levels are significantly elevated due to excess body fat. As a result, these women are particularly vulnerable to breast tumors that have estrogen receptors.
In light of this information, it makes sense that over 70% of postmenopausal women diagnosed with breast cancer were obese. In 2002, after over a decade of research on obesity and cancer, the International Agency for Cancer Research officially stated that, “excess body weight is an avoidable cause of post-menopausal breast cancer.” Once obese women develop breast cancer, their weight also causes far worse outcomes. A study of 1436 women diagnosed with breast cancer in 1996-1997 showed that women who gained weight after diagnosis had a significantly worse survival rate than women who did not gain weight. This 2005 research, led by E.M. Velie from Michigan State University, proved that there is a two-fold increase in risk for death from breast cancer in obese women.
But what exactly happens in fat tissue that makes obese people susceptible to cancer? What else is different in postmenopausal women that makes these women especially vulnerable to breast cancers?
Increased Insulin Levels
One reason for the link between obesity and cancer is that excess fat in obese and overweight people leads to resistance to insulin, a hormone used by our bodies to either convert sugar into energy or store it for future use. Without insulin, there will be high levels of unused, unprocessed sugar in the bloodstream. The term “insulin resistance” should sound familiar because it causes diabetes, a condition that is commonly associated with obesity.
Though insulin resistance is quite common, we still do not know what causes this insulin resistance in obese people. Dr. Olga Hardy from the University of Massachusetts Medical School offers one explanation: cells essentially become “poisoned” by fat. When fat tissue cannot store excess fat, fat accumulates inappropriately in muscle and liver cells. The accumulation of fat limits the functionality of these cells and prevents them from using insulin, resulting in excess, unused insulin and unconverted sugar floating around in the bloodstream. This extra sugar is dangerous because malignant cancer cells use this sugar to replicate.
Dr. Barry Sears of the Inflammation Research Foundation offers another explanation, hypothesizing that our fat releases products that can block the insulin-signaling process. When that happens, no matter how much insulin we have in our blood, our cells cannot use insulin since the signaling pathway is muted by these products. Insulin will try to communicate with cells to help process the sugars, but the cells will not be able to “hear” the insulin because of the products from fat that interfere and silence this communication. This silencing subsequently causes blood sugar levels to build up in the blood since insulin is not being used to break down these sugars. The increased sugar in the blood consequently supplies food to cancer cells.
We have established that insulin resistance exists in obese people, but this resistance does more than create food for cancer cells. It also increases the growth factors in the bloodstream according to Ruth Patterson and her team from Moore’s USCD Cancer Center. These growth factors are signals that tell cells to replicate. More insulin in the bloodstream leads to more growth factors telling cancer cells to multiply.
So, in other words, obese people experience insulin resistance, which results in too much insulin and sugar in their bodies. The sugar supplies nutrients for cell growth, and the insulin tells these cancer cells to grow. Researchers are looking at drugs to target these high insulin levels, specifically with metformin, a drug used to treat type 2 diabetes. Research so far has shown that metformin has reduced growth of most breast-cancer cells, but we need to know more about long-term effects of this drug.
Affected Reproductive Hormone Levels
All overweight and obese people are susceptible to insulin resistance and the uncontrolled cell division that results from it. However, fat tissue not only affects insulin levels, but also estrogen levels. Postmenopausal women have stopped releasing eggs and producing estrogen in their ovaries, so their fat is their only source of estrogen. As a result, excess fat in postmenopausal obese women means that their levels of estrogen are abnormally high. An abnormally high level of estrogen is dangerous because estrogen is a driving force behind most breast cancers. Research by Neil Iyengar from Memorial Sloan-Kettering Cancer Center has shown that postmenopausal women are at a much higher risk of developing tumors that express estrogen receptors. These tumors account for about 60% of breast cancers according to research conducted in Sirai Hospital, Italy.
Estradiol is the specific estrogen thought to stimulate the reproduction of breast cells and mutations. Postmenopausal women have higher rates of breast cancer than premenopausal women, so it would make sense that they must have high levels of estradiol since this hormone helps replicate breast cells. But compared to premenopausal women, postmenopausal women have less estradiol in their bodies since the ovaries no longer produce substantial amounts of estrogen. They are, however, the most susceptible to its effects, and researchers do not know why. Though it has not been directly proven that estrogen causes breast cancer, it has been shown by Ruth Patterson from UCSD that women with hormone levels in the top 20% have two to three times higher risk of breast cancer compared to the bottom 20%. Therefore, despite not knowing exactly how estradiol or estrogen causes cancer-cell replication, researchers know that hormones are responsible for cancer proliferation.
In addition to high insulin levels and excess estrogen, a last cause of postmenopausal cancer in obese patients is chronic inflammation, a biological process that occurs when our bodies’ white blood cells are released into blood and tissues to protect our bodies from foreign substances. We feel this inflammation when we have a sore throat, a stuffy nose, a swollen ankle, or arthritis, but it is also caused by ordinary experiences like eating too much and being stressed. Diets that are high in saturated fat and trans fats can also induce inflammation, and these eating habits are common in obese and overweight people. As a result, obese people experience high levels of inflammation, and many cancers arise at sites of chronic inflammation. In fact, inflammatory response is linked to 15% to 20% of all cancer-related deaths worldwide according to researcher Dr. Neil Iyengar. The release of chemicals by our immune system is meant to be a protective process, but it turns out that too much inflammation has an opposite effect.
Due to the extra fat in obese patients, levels of adipokines, which are signaling molecules involved in inflammation, are significantly higher. Fat releases these adipokines just as it releases estrogen. Many studies show worse prognoses or increased breast-cancer risk in women with higher circulating levels of adipokines. It has not been established yet how exactly the higher levels of adipokines lead to cancer, but it is known that adipokine is one of many indicators of inflammation that are present in breast-cancer tumors.
In addition to secreting adipokines, fat also secretes cytokines, which induce an inflammatory response. Cytokines decrease insulin sensitivity and thus contribute to insulin resistance and all the consequences of insulin resistance including uncontrolled cell growth.
In exploring the causes of cancer in obese people, we are constantly reminded that there is still much to be discovered. We know from the past 25 years of research that excess fat results in too much insulin and sugar in the bloodstream, which in turn feeds cancer cell growth. We know that excess fat also produces extra estrogen, which induces breast cancer in postmenopausal women because many breast cancers have estrogen receptors. Similarly, we have discovered that breast cancers often grow in sites of inflammation that are indirectly caused by poor diet. Researchers have made significant progress, but much work needs to be done to understand the exact pathways between signaling molecules and cancer, the effectiveness of diet and exercise in reducing cancer risk, and more.
Luckily, the scientific community recognizes this major health risk, so they are focusing resources to discover new research models and information about obesity and cancer. The National Cancer Institute is driving this movement by funding many new research centers that foster interdisciplinary collaboration. Several human trials are in progress today. One study on obese women examines the effectiveness of diets that are low in fat but high in carbohydrates or diets that are low in carbohydrates but high in fat. Another study looks at how metformin and exercise can impact breast-cancer mortality among the overweight and obese. A different clinical trial will track obese women with heart rate monitors, accelerometers, and GPS devices to analyze the effects of physical-activity energy expenditure on insulin levels. These trials are looking at the best way to help us lose weight and prevent these cancers.
With significant research in progress, hopefully we will have more answers in the next 25 years.
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