5-fluorouracil Toxicity malady

MalaCards: 5-fluorouracil Toxicity, also known as 5-@fluorouracil toxicity, is related to dihydropyrimidine dehydrogenase deficiency and dihydropyrimidinase deficiency. An important gene associated with 5-fluorouracil Toxicity is DPYS (dihydropyrimidinase), and among its related pathways are Beta-alanine metabolism and Beta-alanine metabolism. The compounds pyrimidine and thymine have been mentioned in the context of this disorder. Affiliated tissues include breast.

OMIM: 274270

5-fluorouracil toxicity 33 5-@fluorouracil toxicity 43

Diseases related to 5-fluorouracil toxicity by text searches and GeneDecks gene sharing:

(show top 50)    (show all 75)

id	Related Disease	Score	Top Affiliating Genes
1	dihydropyrimidine dehydrogenase deficiency	31.2	DPYS, DPYD
2	dihydropyrimidinase deficiency	29.1	DPYS, DPYD
3	colorectal cancer	27.7	UGT1A1, MTHFR, ABCB1, TYMS, DPYD
4	beta-ureidopropionase deficiency	13.1	DPYD, DPYS
5	dihydropyrimidinuria	13.1	DPYD, DPYS
6	gilbert syndrome	13.0	UGT1A1, DPYD
7	rectum cancer	13.0	TYMS, DPYD
8	factor vii deficiency	12.8	UGT1A1, TYMS
9	leukemia, acute nonlymphocytic	12.8	ABCB1, TYMS
10	recessive developmental delay, small stature, microcephaly and brain calcifications	12.8	DPYS, DPYD
11	kidney cancer	12.7	DPYD, ABCB1
12	hemifacial spasm	12.6	MTHFR, TYMS
13	folic acid deficiency anemia	12.6	TYMS, MTHFR
14	adult acute lymphocytic leukemia	12.6	MTHFR, TYMS
15	cardia cancer	12.6	TYMS, MTHFR
16	pediatric osteosarcoma	12.5	MTHFR, TYMS
17	neural tube defect	12.5	MTHFR, TYMS
18	soft tissue sarcoma	12.3	ABCB1, TYMS, DPYD
19	urinary bladder cancer	12.3	ABCB1, TYMS, DPYD
20	bladder carcinoma	12.2	TYMS, DPYD, ABCB1
21	liver cancer	12.2	TYMS, DPYD, ABCB1
22	hyperuricemia	12.1	MTHFR, TYMS
23	pancreatic carcinoma	12.1	DPYD, TYMS, ABCB1
24	peripheral neuropathy	12.0	MTHFR, DPYD, ABCB1
25	acute lymphoblastic leukemia, childhood	12.0	TYMS, ABCB1, MTHFR
26	childhood leukemia	12.0	TYMS, ABCB1, MTHFR
27	osteonecrosis	12.0	ABCB1, TYMS, MTHFR
28	breast-ovarian cancer	11.9	TYMS, MTHFR, ABCB1
29	graft versus host disease	11.9	TYMS, ABCB1, MTHFR
30	hearing loss	11.9	DPYD, MTHFR, UGT1A1
31	leukopenia	11.8	TYMS, ABCB1, UGT1A1, DPYD
32	gastric adenocarcinoma	11.8	ABCB1, MTHFR, TYMS
33	neutropenia	11.8	ABCB1, TYMS, DPYD, UGT1A1
34	diarrhea	11.8	UGT1A1, ABCB1, TYMS, DPYD
35	non-small cell lung carcinoma	11.8	ABCB1, TYMS, DPYD, UGT1A1
36	thrombosis	11.8	MTHFR, TYMS, ABCB1
37	kaposi's sarcoma	11.7	UGT1A1, TYMS, ABCB1
38	thyroid cancer	11.7	UGT1A1, DPYD, TYMS
39	gallbladder carcinoma	11.5	ABCB1, DPYD, MTHFR, TYMS
40	squamous cell carcinoma of the head and neck	11.5	TYMS, MTHFR, DPYD, ABCB1
41	cervical carcinoma	11.5	DPYD, MTHFR, ABCB1, TYMS
42	esophageal cancer	11.5	MTHFR, TYMS, DPYD, ABCB1
43	lung cancer susceptibility	11.5	MTHFR, ABCB1, TYMS
44	epithelial ovarian cancer	11.5	DPYD, TYMS, ABCB1, MTHFR
45	nasopharyngitis	11.5	DPYD, MTHFR, ABCB1, TYMS
46	esophageal squamous cell carcinoma	11.5	TYMS, ABCB1, MTHFR, DPYD
47	peritonitis	11.5	MTHFR, ABCB1, TYMS, DPYD
48	ovarian carcinoma	11.4	TYMS, DPYD, MTHFR, ABCB1
49	endometrial cancer	11.4	UGT1A1, TYMS, MTHFR, ABCB1
50	cervical cancer	11.4	ABCB1, TYMS, DPYD, MTHFR

Clinical features from OMIM: 274270

Approved drugs:

Drug clinical trials:

MalaCards organs/tissues related to 5-fluorouracil toxicity:

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Articles related to 5-fluorouracil toxicity:

(show all 16)

id	Title	Authors	Year	Affiliating Genes
1	Prediction of irinotecan and 5-fluorouracil toxicity and response in patients with advanced colorectal cancer. (20177420)	Glimelius B.... Wadelius M.	2010	TYMS, ABCB1, MTHFR
2	Intragenic deletions and a deep intronic mutation aff ecting pre-mRNA splicing in the dihydropyrimidine dehydrogenase gene as novel m echanisms causing 5-fluorouracil toxicity. (20803296)	Van Kuilenburg A.B.... Gross E.	2010	DPYD
3	Two cases of 5-fluorouracil toxicity linked with gene variants in the DPYD gene. (19822137)	Ofverholm A.... EnerbAock C.	2010	DPYD
4	Dihydropyrimidine dehydrogenase gene variation and se vere 5-fluorouracil toxicity: a haplotype assessment. (19530960)	Amstutz U.... LargiadA"r C.R.	2009	DPYD
5	5-Fluorouracil toxicity-attributable IVS14 + 1G > A mutation of the dihydropyrimidine dehydrogenase gene in Polish colorectal cancer patients. (18443386)	Sulzyc-Bielicka V.... Ciechanowicz A.	2008	DPYD
6	Pyrimidine degradation defects and severe 5-fluorouracil toxicity. (15571261)	Van Kuilenburg A.B.... Van Gennip A.H.	2004	DPYS
7	Mutations in exon 14 of dihydropyrimidine dehydrogenase and 5-Fluorouracil toxicity in Portuguese colorectal cancer patients. (15017333)	Salgueiro N.... Castedo S.	2004	DPYD
8	Dihydropyrimidinase deficiency and severe 5-fluorouracil toxicity. (14555507)	Van Kuilenburg A.B.... Van Gennip A.H.	2003	DPYS
9	Denaturing high performance liquid chromatography analysis of the DPYD gene in patients with lethal 5-fluorouracil toxicity. (12912951)	Ezzeldin H.... Diasio R.	2003	DPYD
10	Identification of novel mutations in the dihydropyrimidine dehydrogenase gene in a Japanese patient with 5-fluorouracil toxicity. (9865912)	Kouwaki M.... Wada Y.	1998	DPYD
11	Semi-automated radioassay for determination of dihydropyrimidine dehydrogenase (DPD) activity. Screening cancer patients for DPD deficiency, a condition associated with 5-fluorouracil toxicity. (9323539)	Johnson M.R.... Diasio R.B.	1997	DPYD
12	Molecular basis of the human dihydropyrimidine dehydrogenase deficiency and 5-fluorouracil toxicity. (8698850)	Wei X.... Fernandez-Salguero P.	1996	DPYD
13	Severe 5-fluorouracil toxicity in a woman treated for breast cancer with concurrent osteogenesis imperfecta and dehydrogenase deficiency (8680084)	Beuzeboc P.... Pouillart P.	1996	DPYD
14	Severe 5-fluorouracil toxicity possibly secondary to dihydropyrimidine dehydrogenase deficiency in a breast cancer patient with osteogenesis imperfecta. (8664058)	Beuzeboc P.... Pouillart P.	1996	DPYD
15	cDNA cloning and chromosome mapping of human dihydropyrimidine dehydrogenase, an enzyme associated with 5-fluorouracil toxicity and congenital thymine uraciluria. (8083224)	Yokota H.... Gonzalez F.J.	1994	DPYD
16	Severe 5-fluorouracil toxicity secondary to dihydropyrimidine dehydrogenase deficiency. A potentially more common pharmacogenetic syndrome. (1648430)	Harris B.E.... Diasio R.B.	1991	DPYD

Genes related to 5-fluorouracil toxicity according to GeneCards:

id	Symbol	Description	Score	GeneCards Section Context
1	DPYS	dihydropyrimidinase	11.0	Publications
2	UGT1A1	UDP glucuronosyltransferase 1 family, polypeptide A1	11.0	Publications
3	DPYD	dihydropyrimidine dehydrogenase	11.0	Publications
4	TYMS	thymidylate synthetase	11.0	Publications
5	MTHFR	methylenetetrahydrofolate reductase (NAD(P)H)	11.0	Publications
6	ABCB1	ATP-binding cassette, sub-family B (MDR/TAP), member 1	11.0	Publications

Pathways related to 5-fluorouracil toxicity according to GeneDecks:

(show all 21)

id	Pathway	Score	Top Affiliating Genes
1	Beta-alanine metabolism10	9.8	DPYD, DPYS
2	Beta-alanine metabolism41	9.8	DPYS, DPYD
3	Erlotinib Pathway, Pharmacokinetics34	9.8	ABCB1, UGT1A1
4	Codeine and Morphine Pathway, Pharmacokinetics34	9.8	UGT1A1, ABCB1
5	Irinotecan Pathway, Pharmacokinetics34	9.7	UGT1A1, ABCB1
6	Atorvastatin/Lovastatin/Simvastatin Pathway, Pharmacokinetics34	9.7	ABCB1, UGT1A1
7	Irinotecan Pathway, Pharmacodynamics34	9.7	UGT1A1, ABCB1
8	Pantothenate and CoA biosynthesis20	9.7	DPYS, DPYD
9	Etoposide Pathway, Pharmacokinetics/Pharmacodynamics34	9.6	UGT1A1, ABCB1
10	Pyrimidine metabolism38	9.6	DPYS, DPYD
11	Drug metabolism - other enzymes20	9.4	DPYS, DPYD, UGT1A1
12	Statin Pathway - Generalized, Pharmacokinetics34	9.4	UGT1A1, ABCB1
13	Fluoropyrimidine Pathway, Pharmacodynamics34	9.3	TYMS, MTHFR
14	Antimetabolite Pathway - Folate Cycle, Pharmacodynamics34	9.3	MTHFR, TYMS
15	Fluoropyrimidine Pathway, Pharmacokinetics34	9.3	DPYS, DPYD, TYMS
16	beta-Alanine metabolism20	9.2	DPYS, DPYD
17	Pyrimidine metabolism20	9.2	DPYS, DPYD, TYMS
18	One carbon pool by folate20	9.0	TYMS, MTHFR
19	Thiopurine Pathway, Pharmacokinetics/Pharmacodynamics34	9.0	MTHFR, TYMS
20	Methotrexate Pathway (Cancer Cell), Pharmacodynamics34	8.8	ABCB1, TYMS, MTHFR
21	Metabolic pathways20	8.0	UGT1A1, TYMS, MTHFR, DPYS, DPYD

Compounds related to 5-fluorouracil toxicity according to GeneDecks:

(show top 50)    (show all 87)

id	Compound	Score	Top Affiliating Genes
1	pyrimidine32 18	11.4	DPYS
2	thymine32 18	11.0	DPYD, DPYS
3	5,6-dihydrothymine32	9.9	DPYS, DPYD
4	dihydrouracil32 18	10.9	DPYS, DPYD
5	nilotinib34 9 9	11.8	ABCB1, UGT1A1
6	atazanavir32 9 9	11.7	UGT1A1, ABCB1
7	tegafur-uracil32	9.7	TYMS, DPYD
8	eniluracil32	9.7	TYMS, DPYD
9	raltitrexed34 9 9	11.7	DPYD, TYMS
10	2-deoxyuridine-5-monophosphate32	9.7	DPYD, TYMS
11	5-fluoro-2-deoxyuridine-5-monophosphate32	9.7	DPYD, TYMS
12	bvdu32	9.7	DPYD, TYMS
13	idurd32	9.7	TYMS, DPYD
14	tegafur32 34	10.7	DPYD, TYMS
15	trimetrexate32 9 9	11.6	ABCB1, TYMS
16	5-deoxy-5-fluorouridine32	9.6	TYMS, DPYD
17	trimethoprim32 9 9	11.5	ABCB1, TYMS
18	ch2h4folate32	9.4	TYMS, MTHFR
19	p-00732	9.4	DPYD, MTHFR
20	lamotrigine32 9 9	11.4	UGT1A1, ABCB1
21	pemetrexed34 9 9	11.4	MTHFR, TYMS
22	orotic acid32 9 18 9	12.3	TYMS, DPYD
23	b vitamins32	9.3	TYMS, MTHFR
24	bevacizumab34 9 9	11.2	DPYD, MTHFR
25	docetaxel32 34 9 9	12.1	TYMS, ABCB1, DPYD
26	mitomycin c32	9.1	ABCB1, TYMS, DPYD
27	6 mercaptopurine32	9.1	UGT1A1, MTHFR, DPYD
28	phenytoin32 34 9 9	12.1	UGT1A1, MTHFR, ABCB1
29	tomudex32	9.0	TYMS, DPYD
30	tetrahydrofolate32	9.0	TYMS, MTHFR
31	camptothecin32 42 9 9	12.0	DPYD, TYMS, ABCB1
32	quercetin32 42 9 18 9	12.9	TYMS, UGT1A1, ABCB1
33	carboplatin32 34 9 9	11.9	MTHFR, TYMS, ABCB1
34	sn 3832 42	9.8	DPYD, TYMS, UGT1A1, ABCB1
35	cyclophosphamide32 34 9 9	11.8	ABCB1, MTHFR, DPYD
36	etoposide32 42 9 9	11.7	ABCB1, DPYD, TYMS, UGT1A1
37	purine32 18	9.5	DPYD, TYMS, MTHFR, DPYS
38	thiopurine32	8.5	MTHFR, DPYD, TYMS, UGT1A1
39	leucovorin32 34 9 9	11.5	UGT1A1, DPYD, MTHFR, TYMS
40	oxaliplatin32 34 9 9	11.5	DPYD, TYMS, MTHFR, UGT1A1
41	fluorouracil34 9 9	10.4	DPYD, MTHFR, ABCB1, TYMS
42	capecitabine32 34 9 9	11.4	DPYD, MTHFR, ABCB1, TYMS
43	taxane32	8.4	DPYD, MTHFR, ABCB1, TYMS
44	gemcitabine32 34 9 9	11.4	ABCB1, MTHFR, TYMS, DPYD
45	methotrexate32 34 42 9 9	12.4	ABCB1, MTHFR, TYMS, DPYD
46	thymidine32 18	9.1	TYMS, DPYD, UGT1A1, DPYS, MTHFR
47	irinotecan32 34 9 9	11.0	UGT1A1, DPYD, TYMS, ABCB1, MTHFR
48	thymidylate32	8.0	TYMS, DPYD, UGT1A1, MTHFR, ABCB1
49	cisplatin32 34 9 9	11.0	UGT1A1, ABCB1, TYMS, MTHFR, DPYD
50	5fluorouracil32	7.6	DPYD, DPYS, TYMS, ABCB1, MTHFR, UGT1A1

Biological processes related to 5-fluorouracil toxicity according to GeneDecks:

(show all 7)

id	Name	GO ID	Score	Top Affiliating Genes
1	uracil catabolic process	GO:006212	9.6	DPYD, DPYS
2	thymine catabolic process	GO:006210	9.5	DPYD, DPYS
3	pyrimidine nucleoside catabolic process	GO:046135	9.5	DPYS, DPYD
4	pyrimidine nucleobase catabolic process	GO:006208	9.2	DPYD, DPYS
5	pyrimidine nucleobase metabolic process	GO:006206	9.0	TYMS, DPYS, DPYD
6	nucleobase-containing small molecule metabolic process	GO:055086	8.8	DPYD, TYMS, DPYS
7	small molecule metabolic process	GO:044281	7.3	MTHFR, DPYS, DPYD, TYMS, ABCB1, UGT1A1