A recent announcement by the National Institutes of Health (NIH) that obesity would likely replace tobacco as the leading modifiable risk factor for cancer probably caught many Americans by surprise. Everyone seems to know that cigarettes cause lung and other cancers (although too many still smoke), but only a minority of the general public is aware of the increased risks for the most common cancers associated with overweight and obesity. Endometrial, breast, colon, high-grade prostate, and esophageal cancers, along with many others and a myriad other health risks, have been associated with overweight and obesity. In addition, in many diseases obesity is associated with a worse outcome after a cancer diagnosis, and this again can come as a surprise to the public who often associate weight loss with cancer treatment and advancing illness.
Before we can understand why overweight and obesity have these associations, it is important to consider why the problem is becoming so widespread. Current levels of overweight and obesity are unprecedented. In the United States, and in many other high-income countries, average daily caloric intake has risen significantly since the 1950s. At the same time, our lives have become more sedentary, meaning we might actually need fewer daily calories. The net effect of these societal changes is that we consume more daily calories, on average, than we need. An important and related aside is that although the specific content of our diets is likely to be important, a dominant issue is simply the number of calories we consume beyond what is needed. Fueling all of this, we produce and distribute calories at low cost with extraordinary efficiency. With lower socioeconomic status, the risk of being overweight or obese rises, and a majority of Americans are predicted to be in this group in the coming decades if current trends continue. These “non-medical” factors simply mean that we have changed the shape of Americans and elevated some of their risks.
Why might overweight or obesity be associated with cancer? Once ingested, excess energy is stored in fat cells (adipocytes). If excess stored energy in fat cells was the end of the problem, it might be a cosmetic or mechanical issue (leading to accelerated wear and tear on joints for example). However, these fat cells are not inert. Over time they enlarge as they store more energy, and eventually they can die. The cellular response to their death includes a localized inflammation that has been shown to possibly contribute to the growth and progression of some cancers. For example, the inflammatory signals created by the response to dying fat cells activate the aromatase gene that is responsible for the manufacture of estrogen (the growth driver of hormone receptor-positive breast cancer). This is one of the reasons the research community is increasingly focused on inflammation, but there are many other consequences of obesity, including metabolism and metabolite changes.
The timing of obesity—in childhood, early adulthood, or later—may also matter in terms of the risk for specific cancers. Voluntary weight loss may reverse some of the effects, perhaps even if the person remains well above ideal weight ranges. Surgery to restrict gastric capacity may be effective but has its own risks to consider. The specific foods that form our diets could matter—for example, some may reduce or increase the inflammation associated with obesity—but this too needs careful study.
Clearly, there are a large number of unanswered questions in the realm of weight, diet, and cancer risk, but from a public health perspective we can’t wait for them before we act. We need education and exercise to reduce childhood obesity rates. We need healthier but affordable food options for lower income neighborhoods. And we need to understand why overweight and obesity contribute to cancer so that we can target the pathophysiology when we can’t prevent it.