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

Table 1 Immune-related single nucleotide polymorphism associated with colorectal cancer

Ref.	Size	Analysis	Gene	SNP	Function	Ethnicity	Comment
Montazeri et al[89], 2020	6149 CRC 7337 controls	Meta-analysis	COLCA1/21	rs3802842 (11q23.1)	Immune infiltration of LP	Europeans	Confirmed by Lu et al[49], 20191
			TGFB1, SMAD7,SMAD7	rs1800469, rs12953717, rs4464148	TGFB signaling inhibitor
Law et al[50], 2019	34627 CRC 71379 controls	Meta-analysis	HLA-C	rs3131043 (6p21.33)	Adaptive immunity	Europeans
			HLA-DRB1/DQA1	rs9271770 (6q21.33)	Adaptive immunity
			COLCA1/2	rs3087967 (11q23.1)	Immune LP leukocytes
			FUT2	rs12979278 (19q13.33)	Gut barrier
Lu et al[49], 2019		GWAS	NOD2	rs2066847	Innate immunity	East Asians	Confirmed by Montazeri et al[89], 20202
			GATA3	rs10795668 (10p14)	T cell transcription factor
			SMAD7	rs7229639	TGFB signaling inhibitor
			SMAD7	rs4939827	TGFB signaling inhibitor
			COLCA1/22	rs3802842 (11q23.1)	Immune infiltration of LP
Sanabria-Salas et al[33], 2017	391 CRC	GWAS	IL1B	CGTC haplotype (2q14)	Inflammation	Columbian Africans	Association with AA admixture
Hung et al[85], 2015	15414 CRC 17688 controls	GWAS	SH2B3	rs3184504 (12q24)	Cytokine signaling	Europeans	Confirmed by Schumacher et al[135], 2015
Schumacher et al[135], 2015	18299 CRC, 19656 controls (Europeans), 2098 cases, 6172 controls (Asian 1), 2627 cases, 3797 controls (Asian 2)	Meta-analysis	SH2B33	rs3184504 (12q24.12)	Cytokine signaling	Europeans/Asians	Confirmed by Hung et al[85], 20153
			NOS1	rs73208120 (12q24.22)	ROS production
Wang et al[47], 2013	2535 CRC, 3915 controls (discovery), 2153 CRC, 2630 controls (validation)	GWAS	PPARG	rs9858822	Monocyte activation	Multi-ethnic	High frequency in AA
Tsilidis et al[136], 2009	CLUE II cohort, 208 CRC, 381 controls	GWAS	IL10	rs1800896, rs1800890, rs3024496, rs3024498	Increased IL-10	ND

¹Confirmed by Lu et al[49].

²Confirmed by Montazeri et al[89].

³Confirmed by Hung et al[85].

AA: African-American; CRC: Colorectal cancer; GWAS: Genome-wide association studies; IL: Interleukin; LP: Lamina propria; ROS: Reactive oxygen species; SNP: Single nucleotide polymorphism; TGF: Transforming growth factor; ND: Not determined; HLA: Human leukocyte antigen; FUT2: Fucosyltransferase 2; NOD2: Nucleotide binding oligomerization domain containing protein 2; GATA3: GATA binding protein 3; SH2B3: SH2B adapter protein 3; NOS1: Nitric oxide synthase 1; PPARG: Peroxisome proliferator-activated receptor gamma.

Table 2 Interactions of host genetics (metabolic and immune-related single nucleotide polymorphism) with gut bacteria

Ref.	Size	Analysis	Gene	SNP	Function	Bacteria	Ethnicity	Comment
Knights et al[59], 2014	474 IBD	16S RNA	NOD2	rs5743293, rs104895431, rs104895467, rs2068844, rs2068845, rs5743277, rs5743293	Innate immunity	Enterobacteriaceae	Europeans	IBD
Blekhman et al[122], 2015	93 (HMP)	Metagenomic	LCT	rs2304371, rs3754689	Metabolism	Bifidobacterium, SMB53 (Clostridiaceae)	Multi-ethnic	NS
			GNA12	rs1182182	IBD
Goodrich et al[123], 2016	1126	Fecal 16S rRNA	CD36	rs1360741	Immune-related	Blautia	Europeans	United Kingdom twins
Li et al[137], 2016	10523 IBD, 5726 IBD	Mucosal 16S rRNA	SLC39A8	rs13107325	Immune-related	Composition	ND	IBD
Bonder et al[68], 2016	1514	Metagenomic	C11orf30-LRRC32	rs2155219	IBD	Coprococcus comes/Proteobacteria		AA1 PCa risk
			CCL2	rs3091315, rs3091316	Immune-related	Methonobacteria
			DAP2	rs267939	Innate immunity	Bifidobacterium
			IL23R	rs12141575	Immune-related	Enterobacteriaceae/E. coli
			IL10	rs18008711	Immune-related	Proteobacteria/Sutterella
			MUC22	rs3873352	Barrier defense
			NOD1	rs12669082	Innate immunity	Enterobacteriaceae/E.coli
				rs41524946	Innate immunity	Enteroba cteriaceae/E. coli
				rs55689059	Innate immunity	Enterobacteriaceae/E. coli
				rs55841603	Innate immunity	Enterobacteriaceae/E. coli
			NOD2	rs8056611, rs2357792,	Innate immunity	Enterobacteriaceae/E. coli
			CD209	rs1010046	Innate immunity	Bacteroidetes
Rühlemann et al[138], 2021	8956	16S rRNA/GWAS	FUT2	rs602662	Barrier defense	Bacteroides OTU97_27	Europeans
			BLVRA	rs623108	Innate immunity	Barnesiella spp. OTU99_55

¹Studies include an analysis according to the population origins.

AA: African-American; GWAS: Genome-wide association studies; HMP: Human Microbiome Project; IBD: Inflammatory bowel disease; SNP: Single nucleotide polymorphism; ND: Not determined; NS: Not significant; PCa: Prostate cancer; rRNA: Ribosomal RNA; E. coli: Escherichia coli; FUT2: Fucosyltransferase 2; NOD2: Nucleotide binding oligomerization domain containing protein 2; LCT: Lactase; GNA12: Guanine nucleotide-binding protein alpha-12; CCL2: C-C motif chemokine ligand 2; IL: Interleukin; MUC22: Mucin 22; BLVRA: Biliverdin reductase.