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According to the CDC, colorectal cancer (CRC) is the third leading cause of cancer-related deaths in America. Worldwide, colon cancer is the third most common cancer, afflicting men and women equally. Over the past few decades, trends in CRC incidence have exhibited a decrescendo effect, and this slight decline is largely attributed to screening guidelines. According to recommendations by the US Preventive Task Force, colorectal cancer screening should begin at age 50 with a colonoscopy procedure. Colonoscopy may be performed at an age earlier than 50 relative to family history and specific symptoms.
In the United States, African Americans (AA) in comparison with other groups, are not only diagnosed more often with CRC at an earlier age but also present with more advanced disease and have lower 5-year survival rates. The incidence of CRC is 20% greater in blacks compared to white cohorts. Epidemiological investigations have revealed many underlying factors contributing to the disparities. They include socioeconomic differences, lack of access to care, poor compliance relative to historical mistrust of the medical system, underlying medical conditions such as diabetes, vitamin D levels, and more. Interestingly, a systematic review revealed that despite higher incidence of CRC amongst AA, there was no difference in overall prevalence of precancerous polyps, suggesting that lack of access to screening is what accounts for the elevated incidence and mortality in AA with CRC.
According to some studies, less than 10% of cancers are associated with genetic defects. The majority of cancers are associated with environmental factors such as diet, cigarette smoking, alcohol, stress, and obesity. Diabetes is considered an independent risk factor for cancer and studies reveal an association between diabetes, and CRC specifically. In the US, AA have some of the highest rates of diabetes compared with other groups. Numerous studies reveal a significantly beneficial relationship between adequate vitamin D and CRC risk reduction. Consistently in the literature, it is reported that AA have lower vitamin D level. However, in teasing apart the literature, we find that AA have a genetic difference in a vitamin D binding receptor, which may explain the common findings on low vitamin D in this group. Diabetes and vitamin D are highlighted here to provide insight into other factors associated with racial disparities across CRC literature.
The comparative incidence of CRC for South African blacks and AA is drastically different. According to one study, CRC occurs in 60 per 100,000 per year in AA compared with 5 per 100,000 per year for South African Blacks. In this study, researchers switched diets between the groups. AA in Pittsburgh were provided the traditional South African diet low in meat and fat but rich in fiber while South African blacks were provided the Western diet. Changes in the gut microbiome were observed within 2 weeks of the dietary switch. Researchers also noted a change in epithelial cell proliferation which is associated with cancer development.
In a pilot study, AA in comparison with Caucasian Americans (CA), were found to have less intestinal microbiome diversity with more pro-inflammatory bacteria and fewer anti-inflammatory bacteria. Researchers found a lower relative amount of the anti-inflammatory gut bacteria, Bacteroides fragilis in AA compared to CA. Another anti-inflammatory bacteria that is also associated with diabetes, Akkermansia muciniphila, was found to be lower in AA compared with CA. With regard to overall bacteria categories, AA were found in this study to have an abundance of Bacteriodetes with a reduction in Firmicutes and Actinobacteria categories. Other studies reveal similar differences in gut microbiome between AA and other ethnic groups. Butyrate, an anti-inflammatory and immune-modulating compound produced in the gut by specific bacteria, has also been found to be lower in AA compared with other ethnic groups. Butyrate is produced by bacterial fermentation of dietary fiber.
The role of the immune system in cancer pathology has been extensively documented. Our gut microbiome stimulates our immune system. While it is often mentioned that the immune system resides within the gut, there also exists a link between cancer and the gut. In short, the microbiota contributes to cancer development by its role in immune function, the production of toxic carcinogenic chemicals, the production of inflammatory molecules, and dysbiosis.
Metabolites secreted from intestinal bacteria Lactobacillus casei have been shown to trigger cell death in tumor cells. This same bacteria Lactobacilli has been demonstrated to stimulate natural killer (NK) cells, which are immune cells associated with the destruction of cancer cells. Butryate, a by-product of fiber fermentation in the gut has also been shown to exhibit anti-tumor effects in CRC through different mechanisms. Research also demonstrates viral and fungal dysbiosis in the microbiome of CRC cases. The intestinal microbiome has enormous balancing potential but there is another side to the coin.
Diet is one of the most significant influencers of the intestinal microbiome. Intestinal dysbiosis measured in stool samples of CRC patients demonstrates different bacterial populations relative to healthy controls with normal colonoscopies. CRC patients exhibit stark dysbiosis relative to non-CRC patients with a significant increase in Fusobacterium nucleatum that appears relatively consistent across the literature. There are also significant elevations in Bacteroides fragilis, Escherichia coli, and Enterococcaceae to name a few. Overall, there is a reduction in fiber-fermenting bacteria.
With regard to racial disparities in CRC, it is crucial to evaluate the whole patient. Of utmost importance is access to care and awareness of historical medical mistrust that may create barriers to care and compliance. Encouraging a plant-rich diet is beneficial as fibers in our diet lead to the creation of anti-inflammatory compounds such as butyrate. Plant-rich diets also have a profound effect on metabolic diseases such as obesity and diabetes, both of which are highly prevalent in the AA community and both of which are risk associations for CRC.