Inflammation, microbiome and colorectal cancer disparity in African-Americans: Are there bugs in the genetics?

Figure 2 Interactions between host genetics and microbiome delineate colorectal cancer risk factors. Immune-related risk factors of colorectal cancer (CRC) may combine host genetics [including immune-related single-nucleotide polymorphisms (irSNPs)] and microbiome cues. The genetic regulation (irSNP) of bacteria (Taxa) recognition by the mucosal immunity may mediate the heterogeneity of CRC risk factors between populations which vary by the representation of irSNPs. A: Absence of irSNPs and pathogenic bacteria (no irSNPs/no Taxa) maintain healthy mucosal inflammation and gut barrier; B: Absence of irSNPs with enrichment of pathogenic bacteria (no irSNPs/Taxa) may lead to chronic inflammation that slowly promotes polyp formation; C: Presence of irSNP in absence of pathogenic bacteria may also lead to chronic inflammation that slowly promotes polyp formation; D: Combination of irSNP and pathogenic bacteria (dysbiosis) may trigger a smoldering chronic inflammatory response precipitating early progression of the adenoma-carcinoma sequence. Genome-wide association studies (GWAS) (irSNP as CRC risk) and microbiome GWAS (mGWAS) (bacteria as CRC risk) are poised to miss the association of the irSNP with CRC because of the necessity of a combined occurrence of irSNP and specific bacteria enrichment in the microbiota to increase the CRC risk. However, if the irSNP is linked to the genetic ancestry, population-specific microbiome GWAS will likely detect the association of irSNP and the bacteria as a CRC risk in the population carrying this genetic ancestry. CRC: Colorectal cancer; irSNPs: Immune-related single-nucleotide polymorphisms; GWAS: Genome-wide association studies; mGWAS: Microbiome genome-wide association studies.