The Crucial Role of Diet in Colorectal Cancer Risk

Colorectal cancer (CRC) is the second leading cause of cancer death in the Western world. It afflicts 150,000 Americans, 250,000 Europeans and 1 million people worldwide annually, and nearly one third will die. The global burden of CRC is expected to increase to more than 2.2 million new cases and 1.1 million annual cancer deaths by 2030. Rather than taking a closer look at the root cause of this problem, the response of the medical system to this alarming trend has been the promotion of colon cancer screening without paying much attention to the role of lifestyle factors that have dramatically changed in the past 75 years, in particular dietary changes. Screening with colonoscopies has permitted early detection and recent studies have clearly shown that this early detection is associated with a significant reduction in mortality rates. However, the overall impact of colon cancer screening has been small, particularly among African Americans who shoulder the greatest burden of the disease in the United States. Recently, when I asked an expert on colon cancer screening if individual dietary habits are considered as risk factors to determine how closely individuals with a positive finding on an initial screening colonoscopy have to be followed, the surprising answer was “this would be a great idea”.

“…new cases have been increasing in young and middle-aged adults…”

As is the case for many of our non-communicable chronic diseases, the burden of CRC is rapidly shifting to younger individuals. In the United States, despite declines in older adults, the incidence has been increasing in young and middle-aged adults with 22% of CRC cases occurring in those younger than 55 years in 2013 to 2017. CRC incidence has been on the rise among young adults aged 20 to 39 years since the mid-1980s, and this elevated risk in generations born in the US after 1950 strongly indicates that widespread changes in early-life exposures, such as diet and lifestyle factors, may be a major factor underlying the upward trend in early-onset CRC.

As I have explained in The Gut Immune Connection, colon cancer shows all the hallmarks of a number of diseases that make up the current epidemic of non-communicable chronic diseases affecting all organs in our body, and presenting as such different medical problems as cardiovascular disorders, non-alcoholic fatty liver disease, type 2 diabetes, metabolic syndrome, obesity, autism spectrum disorder, depression, and neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease. These various diseases are not only connected with each other (e.g. the presence of one diagnosis often increases the risk for another), but they share the disease mechanism of low grade systemic immune system activation, occur increasingly in younger age groups and developing countries, and are strongly related to dietary habits and other lifestyle factors, including increased exposure to chemicals and certain medications. For example, studies in Japanese Hawaiians, have demonstrated that it only takes one generation for the immigrant population to assume the colon cancer incidence of the host country, e.g. the US, with adoption of the Western diet playing a major role.

“…diet-induced changes in the interactions between the gut microbiome and the gut-associated immune system are a key mechanism underlying the current epidemic.”

Reviewing the current evidence, I feel strongly that diet-induced changes in the interactions between the gut microbiome and the gut-associated immune system are a key mechanism underlying the current epidemic. It is becoming increasingly clear that one dietary pattern in particular, the Standard American Diet (SAD) contains many of the components responsible for the negative health effects. High consumption of ultra-processed foods, refined sugars (including high fructose corn syrup) and animal products (red meat and animal fats), paired with a greatly reduced consumption of variable fruits and vegetables containing fiber and polyphenols, as well as a low consumption of naturally fermented foods.

A body of evidence suggests that the relationship between the SAD and colon cancer risk is multifactorial. In other words, different dietary components play a role. A study published in the journal Nature Communications in 2015 compared the effect of diet on CRC risk in African Americans and rural Africans. The authors of the study focused on the importance of diet in African Americans and to explore the hypothesis that CRC risk is determined by the influence of the diet on the microbiota to produce molecules that either decreased (anti-neoplastic) or increased (pro-neoplastic) the risk of colon cancer.

“Animal protein and fat intake were two to three times higher in Americans, whereas consumption of complex carbohydrates and fiber, primarily in the form of resistant starch, were higher in Africans.”

They observed that the diets of African Americans here in the United States, and Africans living in rural villages in South Africa, were fundamentally different in preparation, cooking and composition. Animal protein and fat intake were two to three times higher in Americans, whereas consumption of complex carbohydrates and fiber, primarily in the form of resistant starch, were higher in Africans. Looking at colonoscopies, African Americans had more polyps and higher rates of mucosal proliferation. The dietary differences were shown to be associated with profound differences in the gut microbiota. In Americans, the genus Bacteroides dominated, whereas the genus Prevotella dominated in South Africans. The two groups also differed in the functional capacity of their microbes: Africans had higher levels of starch degraders, carbohydrate fermenters and short chain fatty acid (butyrate) producers, while secondary bile acid producers dominated in Americans. It is well known that products of fiber fermentation, in particular the short chain fatty acid butyrate, are anti-inflammatory and anti-neoplastic, while the products of microbial bile acid conjugation, e.g. different types of secondary bile acids, are carcinogenic. These findings suggested two potential mechanisms for diet-associated colon cancer risk: the protective effect of dietary fiber in increasing the production of butyrate, and the pro-neoplastic effect of dietary fat on stimulating bile acid synthesis by the liver.

In summary, considerable epidemiological evidence supports an important role of diet in colon cancer risk. However, it is important to keep in mind that the cause of cancer is multifactorial, including several lifestyle factors and exposure to environmental chemicals and toxins.

Dr. Emeran Mayer is a Distinguished Research Professor in the Departments of Medicine, Physiology and Psychiatry at the David Geffen School of Medicine at UCLA, the Executive Director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience and the Founding Director of the Goodman-Luskin Microbiome Center at UCLA.