Obesity and Cancer in The Scientist

One theme of this blog is the importance of healthy eating and the consequences of obesity, which include an increased risk of at least ten types of cancer. The readers interested to learn in depth about the obesity-cancer connection may find this article from The Scientist useful.

The article states that:
 

This year, obesity overtook smoking as the top preventable cause of cancer death in the U.S., with some 20 percent of the 600,000 cancer deaths per year attributed to obesity.
 
One mechanism that connects obesity to cancer is inflammation. Exacerbating the inflammation problem are diet-related changes in the gut microbiome:
 

Obesity is associated with an overall reduction in gut bacterial diversity, and decreased bacterial richness has been linked to elevated systemic inflammation. Researchers have also demonstrated that high-fat diets are accompanied by impairments in gut barrier function, resulting in higher plasma levels of lipopolysaccharide (LPS), a component of the outer membrane of gram-negative bacteria. Increased LPS levels have been shown to induce metabolic endotoxemia, characterized by elevated adipose tissue macrophage infiltration and proinflammatory cytokine expression. Together, these studies suggest that obesity-related perturbations of the gut microbiome and barrier function associated with a high-calorie diet can induce chronic systemic and adipose tissue inflammation, which is known to play a role in the progression of several cancer types.

Another mechanism whereby obesity can promote cancer is through changes in the signaling between cells, including elevated insulin levels ( as in metabolic syndrome).


Obesity not only increases the risk for developing cancer, but it can result in a more aggressive and invasive form.

In addition to putting people at an increased risk for developing cancer, obesity also worsens a cancer patient’s prognosis. Research from our group and others has shown that a variety of cancers grow at faster rates in obese patients than in lean individuals. Furthermore, obesity appears to increase the chances that a patient’s cancer will metastasize. A variety of factors may underlie the obesity-metastasis link, including circulating factors such as leptin, adiponectin, and IGF-1; adipose tissue remodeling, including alterations in adipose-derived stem cells; and other changes to the tumor microenvironment. Our work in breast and pancreatic cancer, for example, has shown that obesity can drive epithelial-to-mesenchymal transition (EMT), a key mechanism in progression to metastasis.

Obesity can also result in a diminished response to chemotherapy.
 

Unfortunately, the article concludes with the suggestion that weight normalization is an “unrealistic goal,” and we should instead come up with treatments that would allow people to be obese while blocking some of the negative downstream consequences of obesity, including cancer:

Thus, while weight normalization in a significant number of the obese adults worldwide will likely never be a realistic goal, it is also unclear whether this simple reversal of obesity would markedly reduce the cancer burden. A precision-medicine approach that targets key processes dysregulated by obesity may be needed to break the obesity-cancer link. In addition, combination approaches that simultaneously target growth factor, inflammatory, or other key signals will likely have better success than single agents or interventions.

One justification for this conclusion is that 20% of normal weight individuals are metabolically unhealthy; whereas,10% of the obese are metabolically healthy. Therefore, we should concentrate on the downstream metabolic effects rather than on the weight:

The idea that preventing obesity-related cancers depends on targeting the obesity-associated metabolic dysregulation rather than weight is further reinforced by the recent recognition that some 20 percent of normal-weight people are metabolically unhealthy and at increased risk for cancer,14 while approximately 10 percent of obese individuals are metabolically healthy and show no elevated cancer risk.

Of course, 20% and 10% represent minorities of the normal weight and obese populations, respectively. Most of the normal weight people are metabolically healthy; whereas, a very large majority of obese individuals develop metabolic dysfunction. In addition, the concept that metabolically healthy obese exist might be flawed. Therefore, while it is certainly a good idea to come up with treatments that can block the obesity-cancer link, it will also be important to pursue the “unrealistic” goal of reducing overweight and obesity. Thus, in addition to cancer, overweight and obesity contribute to a broad range of other health problems. We can either continue on the absurd road of obesity, or we can try to restore a more normal weight profile for Americans. If we do not try, the vast majority of Americans will be medicated to counteract/ameliorate the effects of obesity; such medications will likely have side effects and increase the already crushing financial burden to the patients and the health care system. It is clear also that if it is difficult to shed the already-accumulated weight, at least we should try our best to prevent the next generation of Americans from becoming overweight/obese.
 

There will be some who will need treatment, particularly those who are metabolically unhealthy even with normal weight and healthy eating. But that should be a minority. The idea that a huge portion of the American population needs to be extensively medicated because we surrender to the “inevitability” of obesity is unacceptable. Perhaps what we need are more research initiatives like this.