Pharmacogenetics research on chemotherapy resistance in colorectal cancer over the last 20 years

Table 1 Some common polymorphisms of genes TYMS, MTHFR, DPYD and UMPS and their potential impact on the functioning of proteins associated with the pharmacology of 5-fluorouracil

dbSNP rs cluster ID	Type of polymorphism	Function	Ref.
Thymidylate synthase (TYMS) (OMIM # 188350)
rs45445694	VNTR		[43-51,68,409-413]
	TSER*2/ TSER*3	TSER polymorphism (TS 2R/3R repeat) is a tandem repeat upstream of the TYMS translational start site containing either double (2R) or triple (3R) repeats of 28-bp sequences
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 45445694
rs34743033	SNP		[44-46,49,50,414]
	TSER*3G>C	TSER*2/*3 repeat is studied together with a G to C SNP within the second repeat of the TSER*3 allele
		TSER*3C allele = decrease transcriptional activity of TYMS
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 34743033
rs151264360	Del/Ins		[44,46,49,51,72,415]
	TS 1494del6bp	-6-bp deletion, decreased stability of TS mRNA
		+6-bp insertion, increased stability of TS mRNA
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 151264360
Methylenetetrahydrofolate reductase (MTHFR) (OMIM # 607093)
rs1801133	SNP		[66-69,72,313,316,362]
	677C>T	At codon 222 in exon 4 (Ala → Val)
		Reduces enzymatic activity and increased thermolability
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 1801133
rs1801131	SNP		[67-69,72,313,316]
	1298A>C	At codon 429 in exon 7 (Glu → Ala)
		Reduces MTHFR activity
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 1801131
rs4846051a	SNPs		[71,416]
	1305T>C	At codon 435 (synonymous), effect unknown
rs201095365b	1798G>A	At codon 600 (Glu → Lys), effect unknown
ahttp://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 4846051
bhttp://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 201095365
Dihydropyrimidine dehydrogenase (DPYD) (OMIM # 612779)
rs3918290	SNP		[88,412,417,418]
	IVS14+1G>A	Exon 14 is skipped as a result of the G → A translocation at intron 14, inactive enzyme is formed
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 3918290
rs75017182	SNP		[92,419]
	c.1129– 5923C>G	Cryptic splice donor site leads to a 44 bp fragment of intron 10 insert in mrna, frameshift and premature stop codon in exon 11
		Associated with toxicity
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 75017182
-	SNPs		[92,417]
	IVS5+18G>A	G → A translocation at intron 5, effect unknown
	IVS6+139G>A	G → A translocation at intron 6, effect unknown
	IVS9–51T>G	T → G translocation at intron 9, effect unknown
rs1801265	SNP		[85,420-424]
	85T>C	At codon 29 in exon 2 (Cys → Arg)
		Decreased expression
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 1801265
rs2297595	SNP		[420,421,424-427]
	496A>G	At codon 166 in exon 6 (Met → Val)
		Significantly conserved site close to the Fe-S motif, may disrupt electron transport
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 2297595
rs1801159	SNP		[421,424,427-430]
	1627A>G	At codon 543 in exon 13 (Ile → Val)
		Decreased expression
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 1801159
rs55886062	SNP		[92,422,431-434]
	1679T>G	At codon 560 in exon 13 (Ile → Ser)
		Might destabilize FMN (flavine mononucleotide) binding domain
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 55886062
rs1801160	SNP		[424,428]
	2194G>A	At codon 732 in exon 18 (Val → Ile)
		Decreased expression
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 1801160
rs67376798	SNP		[92,412,417,422,425,426, 432,435-437]
	2846A>T	At codon 949 in exon 22 (Asp → Val)
		Significantly conserved site near the Fe-S motif, may disrupt cluster formation and electron transport and lead to lower DPD activity
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 67376798
Uridine monophosphate synthetase (UMPS) [OMIM #613891]
rs121917890a	SNPs		[122-126]
	213A>G	At codon 96 (Arg → Gly), effect unknown
rs121917892b	326T>G	At codon 109 (Val → Gly), effect unknown
rs1801019c	638G>C	At codon 213 (Gly → Ala), increase activity
rs2291078d	1050T>A	At codon 350 (synonymous), effect unknown
rs121917891e	1285G>C	At codon 429 (Gly → Arg), effect unknown
rs3772809f	1336A>G	At codon 446 (Ile → Val), effect unknown
ahttp://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 121917890
bhttp://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 121917892
chttp://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 1801019
dhttp://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 2291078
ehttp://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 121917891
fhttp://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 3772809

SNP: Single nucleotide polymorphism.