Gene, genetics and genetic medicines in gastroenterology: Current status and its future

Table 8 Genes that help in prediction and poor prognostications[56-89]

Disease	Prediction and prognostication	Genes	Ref.
FAP	Profuse polyposis	APC codon 1250-1464, 1250-1311, 1309-1324	Nagase et al[56]; Enomoto et al[57]; Ficari et al[58]; Walon et al[59]; Gebert et al[60]
	Desmoid tumors	APC codon 1924, 1962, 1444-1560, 1403-1987	Caspari et al[61]
	Upper gastrointestinal polyps	1445-1578	Davies et al[62]
	Gastric adenomas	1403-1987	Caspari et al[61]
	Multiple extracolonic manifestations	3’14451995, 3’1403	Caspari et al[61]
	CHRPE	311-1444, 413-1387, 542-1309	Caspari et al[61]
Crohn’s disease	Stenotic/structuring behavior	NOD2, TLR4, IL-12B, CX3CR1, IL-10, IL-6	Tsianos et al[63]
	Penetrating/fistulizing behavior	NOD2, IRGM, TNF, HLADRB1, CDKAL1	Tsianos et al[63]
	Inflammatory behavior	HLA	Tsianos et al[63]
	Granulomatous disease	TLR4/CARD15	Tsianos et al[63]
	Upper gastrointestinal	NOD2, MIF	Tsianos et al[63]
	Ileal	IL-10, CRP, NOD2, ZNF365, STAT3	Tsianos et al[63]
	Ileocolonic	ATG16 L1, TCF-4 (TCF7 L2)	Tsianos et al[63]
	Colonic	HLA, TLR4, TLR1, TLR2, TLR6
	Crohn’s disease activity	HSP70-2, NOD2, PAI-1, CNR1	Tsianos et al[63]
	Surgery	NOD2, HLA-G	Tsianos et al[63]
	Dysplasia and cancer	FHIT
	Extraintestinal manifestations	CARD15, FcRL3, HLADRB103	Tsianos et al[63]
Ulcerative colitis
	Extensive colitis and increased colectomy risk	HLA-DRB1 alleles, CASP9 gene on 1p36, ATG16 L1 T300A	Nam et al[64]
	May influence severity and steroid dependence	IL23R, STAT3, HSP70-2, MDR1	Nam et al[64]
	Early response to infliximab	IL23R higher gene expression IL-17A and IFN-γ	Jürgens et al[65]; Rismo et al[66]
	Good response to therapy	TNF ALPHA expression	Olsen et al[67]
	Non response to infliximab	PR3-ANCA	Yoshida et al[68]
	Favorable response to treatment	FCGR3A, TNFRSF1A, IL-6, and IL-1B
	Failure of steroid therapy	MDR1 (ABCB1), TNFα (-308/-857 SNPs), HLA-DQA1 05/DRB1, NOD2, ATG16 L1, IL13RA2, IL6, IL11, TNFAIP6
	Unfavorable response to therapy (IBD)	TLR2 and TLR9 show a negative correlation	Sazonovs et al[69]
	Development of ADA against infliximab and adalimumab	HLA-DQA1 05	Sazonovs et al[69]
	Development of ADA against infliximab	HLA-DRB1
Celiac disease
	Increase severity of disease	DQA1 05 and DQB1 02, homozygous for DQ2.5 haplotype, second copy of the DQB1 0201	Murray et al[70]; Stanković et al[71]
Hereditary pancreatitis	Increased risk of disease	PRSS1 pathogenic variants include p.Asn29Ile and p.Arg122His, p.Asn29Ile and p.Arg122His	Avanthi et al[72]; Whitcomb[73]
	Increased severity and early onset of disease	SPINK1, c.101A>G p.Asn34Ser and SPINK1, c.56-37T>C	Abass et al[74]
GIST
	Increase severity and relapse	Exon 11, 13, 17, c-KIT mutation; SDH deficient, BRAF mutation	Zhang and Liu[75]
Colorectal cancer	Increased severity and predict recurrence	P53, KRAS codon 12, loss of 18q	Andreyev et al[76]; Walther et al[77]
HCC	Increased severity	EZH2, STAT3, YB-1, ANLN, NLRC5
	Poor prognosis	Overexpression of CDCA5	Wang and Lai[78]; Hashemi et al[79]; Svinka et al[80]; Chao et al[81]; Jia et al[82]; Peng et al[83]
		Overexpression of CDCA5	Tian et al[84]
Gall bladder cancer	Increased severity of disease	SERPINB5 (maspin) KRAS, E-cadherin/beta-catenin, PML, P53, CDKN21 loss	Kim et al[85]; Hirata et al[86]; Chang et al[87]
Intra hepatic cholangiocarcinoma	Increased severity and large tumor size	BRAF	Xin et al[88]
Pancreatic cancer	Poor prognosis	KRAS (G12D/G12V/G12R), CDKN2A (p16), SMAD4 (DPC4)	Zhou et al[89]

FAP: Familial adenomatous polyposis; HCC: Hepatocellular carcinoma; GIST: Gastrointestinal stromal tumor; CHRPE: Congenital hypertrophy of the retinal pigment epithelium; ADA: Anti-drug antibodies; IBD: Inflammatory bowel disease; TNF-α: Tumor necrosis factor alpha.