The Link between Fat and Cancer

Everyone seems to know that being overweight and obese is bad for your health, but many people don’t know exactly why. Increased cancer risk is just one reason, but a big and important one.

Data indicate 14% of cancer deaths in men and up to 20% of cancer deaths in women are attributable to obesity. A 2002 comprehensive expert review by the International Agency for Research on Cancer (IARC), the same body that classifies carcinogens, concluded that, globally, obesity is a cause of 11% of colon cancer cases; 9% of postmenopausal breast cancer cases; 39% of endometrial cancer cases; 25% of kidney cancer cases; and 37% of esophageal cancer cases.

 

More recent data from the American Cancer Society (ACS) suggests that being overweight and obesity are also related to mortality from liver cancer, pancreatic cancer, non-Hodgkin lymphoma, and myeloma (cancer of plasma cells). Finally, most recently, an expert panel with the American Institute for Cancer Research (AICR) and World Cancer Research Fund (WCRF) conducted an updated review and concluded there is convincing evidence for a relation between obesity and esophageal, pancreatic, colorectal, postmenopausal breast, endometrial and kidney cancers. They found evidence was probable for a relation between obesity and gallbladder cancer, as well as, abdominal fat and an increased risk of pancreatic, endometrial and postmenopausal breast cancers. New evidence also suggests that obesity increases the risk of developing the aggressive forms of prostate cancer.

Overall, we estimate that being overweight and obesity causes approximately 20% of all cancer cases. Experts now estimate that the total health burden of being overweight and obesity, combined with a lack of physical activity and poor diet, equal – or might even exceed – that for cigarette smoking.

 Why does obesity increase cancer risk?
Understanding the mechanism by which obesity increases cancer risk requires us to understand the tumor biology, and it also helps us target our prevention strategies. While we often talk of cancer as one disease, tumors in different parts of the body act differently (which is why treatment approaches vary by tumor site). This means that the mechanism by which one cancer develops may not be the same mechanism for another. Cancers are also complex and develop over many years, or sometimes decades. As a result, more than one mechanism can link a complex cause, like obesity, with this complex disease. This means that different mechanisms can initiate the tumor early from those that promote its growth or metastasis later.

For example, in colon cancer, evidence points to insulin pathways mediating the effect of BMI and risk. We know that people with diabetes, a disease characterized by dysregulation of insulin, have a higher risk of colon cancer. Studies of blood glucose (blood sugar) levels and colon cancer show a direct relation between higher glucose and subsequent risk. Providing further biologic rationale, c-peptide, a marker of insulin production, also shows this positive relation. In animal studies, injecting insulin (as opposed to saline) significantly increases colon cancer risk. In addition to insulin mediating the relation between obesity and colon cancer, we see a role for it in endometrial and pancreatic cancers.

While strong evidence points to hyperinsulinemia as a direct pathway from obesity to colon cancer, we also have good evidence that inflammation is an important risk factor for colon cancer. Obesity promotes systemic inflammation.

Non-steroidal anti-inflammatory drugs (NSAIDs) have shown promise as chemopreventive agents, but concerns exist regarding the side effects associated with their long-term use. In observational studies, where large groups of healthy people are followed over many years, regular use of aspirin and NSAIDs is associated with a decreased risk of colon cancer and colon polyps, which often progress into colon cancer if not removed. Celecoxib, a prescription anti-inflammatory drug, has been shown to decrease the number of colon polyps in people with inherited polyp syndromes. All of this points to inflammation as key in colon carcinogenesis. Since we know obesity increases levels of inflammation in the body, it is likely that inflammation is also part of the obesity-colon cancer mechanism. (Note: NSAID and COX-2 use is associated with some serious side effects, highlighting the challenges of relying on chemoprevention as a cancer prevention strategy. Before starting regular NSAID use, talk to your doctor.)

In cancers of reproductive organs, such as endometrial and ovarian cancers, obesity may also act through hormonal mechanisms. Adipose, or fatty, tissue is estrogenic;  and estrogen is a powerful hormone, acting to increase cell proliferation and inhibit cell death in the endometrial tissue. This combination promotes cancer growth.

Finally, obesity can also place mechanical stress on the body that increases cancer risk.  For example, obesity increases the risk of hypertension (high blood pressure), an established risk factor for kidney cancer.

Regardless of the mechanism (or mechanisms) at play, it is clear that being overweight and obese increase cancer risk. We also know that changing weight can change cancer risk. Gaining weight from early adulthood to later in life, even modestly, increases cancer risk. For example, in a Canadian study, men who gained 21 kg (46.2 lbs) or more since age 20 were at a 60% increased risk of colorectal cancer as compared to men who had gained 1-5 kg (2.2 to 11 lbs). Another study of men and women found that, compared to those who had remained BMI-stable, those who increased their BMI from age 30 or 50 to cancer diagnosis were at a 25-35% higher risk of colorectal cancer. Similarly, a study of US nurses found that women who lost 10 kg (22 lbs) or more after menopause, and kept it off, saw a 50% reduction in breast cancer risk.  Losing 10 kg might seem like an impossible task for some women, but that same study found that women losing just 2 kg (4.4 lbs) still saw their risk go down.

Conclusion

Obesity causes a substantial proportion of all cancers, and emerging evidence suggests adult weight loss reduces cancer risk. To maintain a healthy weight, focus on eating a diet rich in fruits, vegetables and whole grains, avoid sugary beverages and junk food, and build physical activity into your daily life. These factors not only help in maintaining a healthy weight, but we have evidence that they protect against cancer on their own. For example, people who are physically active have a significantly lower risk of several cancers, including colon, breast and endometrial. Fruits, vegetables and whole grains contain important compounds, like folate, which we’ve seen in some studies to lower pancreatic cancer risk. It might sound cliché, but increasing physical activity and avoiding weight gain are, and have always been, important tools in the fight against cancer.

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