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.

Table 2 Gene/protein expression or metabolic enzyme activity in colorectal cancer cells and correlation with outcome of patients receiving fluoropyrimidine-based chemotherapy

Treatment setting	Method	Patients (n)	Better response to chemotherapy	Form of the disease	Ref.
Thymidylate synthase (TYMS) [OMIM # 188350]
5-FU	RT-PCR	29	Low expression	mCRC	Iyevleva et al[24]
5-FU	RT-PCR	39	Low expression	CRC	Ishida et al[25]
5-FU	IHC	57	Low expression	mCRC	Hosokawa et al[26]
5-FU	IHC	62	Low expression	aCRC	Ciaparrone et al[27]
5-FU	RT-PCR	92	Low expression	CRC	Nakajima et al[28]
5-FU	RT-PCR	309	Low expression	CRC	Kornmann et al[29]
5-FU	IHC	391	Not significant	aCRC	Westra et al[438]
5-FU	IHC	945	Not significant	CRC	Soong et al[107]
FUdR	IHC	36	Low expression	mCRC	Davies et al[31]
5-FU/LV or 5-FU	RT-PCR	29	Low expression	mCRC	Kornmann et al[32]
5-FU/LV	RT-PCR	33	Low expression	aCRC	Salonga et al[17]
5-FU/LV	RT-PCR	36	Low expression	mCRC	Lenz et al[7]
5-FU/LV	RT-PCR	42	Low expression	CRC	Leichman et al[19]
5-FU/LV	RIA	102	Low expression	mCRC	Etienne et al[33]
5-FU/OX	RT-PCR	45	Low expression	aCRC	Shirota et al[34]
5-FU/MTX	IHC	108	Low expression	aCRC	Paradiso et al[35]
5-FU or 5-FU/MTX or 5-FU/LV	IHC	24	Not significant	aCRC	Belvedere et al[439]
5-FU or 5-FU/MTX or 5-FU/LV	IHC	27	Not significant	mCRC	Aschele et al[23]
5-FU or 5-FU/MTX or 5-FU/LV	IHC	48	Low expression	mCRC	Aschele et al[36]
5-FU/LV/CPT-11	RT-PCR	13	Low expression	aCRC	Yanagisawa et al[37]
5-FU/LV/CPT-11	IHC	54	Low expression	aCRC	Bendardaf et al[38]
5-FU/LV/CPT-11	IHC	57	Not significant	aCRC	Paradiso et al[440]
UFT/LV	RT-PCR	37	Low expression	mCRC	Ichikawa et al[39]
Capecitabine	RT-PCR	37	Not significant	aCRC	Vallböhmer et al[97]
Capecitabine	IHC	39	Not significant	CRC	Lindebjerg et al[441]
Capecitabine/CPT-11	IHC	556	Not significant	aCRC	Koopman et al[110]
5-FU-based therapy	IHC	681	Not significant	CRC	Karlberg et al[442]
Dihydropyrimidine dehydrogenase (DPYD) (OMIM # 612779)
5-FU	RT-PCR	29	Not significant	mCRC	Iyevleva et al[24]
5-FU	RT-PCR	39	Not significant	CRC	Ishida et al[25]
5-FU	IHC	62	Low expression	aCRC	Ciaparrone et al[27]
5-FU	IHC	303	Low expression	CRC	Jensen et al[443]
5-FU	RT-PCR	309	Low expression	CRC	Kornmann et al[29]
5-FU	IHC	391	Not significant	aCRC	Westra et al[438]
5-FU	IHC	945	Not significant	CRC	Soong et al[107]
5-FU/LV	RT-PCR	33	Low expression	aCRC	Salonga et al[17]
UFT/LV	RT-PCR	37	Low expression	mCRC	Ichikawa et al[39]
5-FU/LV/CPT-11	RT-PCR	13	Not significant	aCRC	Yanagisawa et al[37]
Capecitabine	RT-PCR	37	Low expression	aCRC	Vallböhmer et al[97]
Capecitabine/CPT-11	RT-PCR	67	Not significant	aCRC	Meropol et al[98]
Capecitabine/CPT-11	IHC	556	Low expression	aCRC	Koopman et al[110]
5-FU-based therapy	ELISA	64	Low expression	aCRC	Oi et al[444]
5-FU-based therapy	RT-PCR	102	Low expression	CRC	Lassman et al[445]
5-FU-based therapy	RT-PCR	144	Low expression	aCRC	Gustavsson et al[446]
5-FU-based therapy	IHC	150	Low expression	aCRC	Tokunaga et al[447]
Thymidine phosphorylase (TYMP) (OMIM # 131222)
5-FU	IHC	62	Not significant	aCRC	Ciaparrone et al[27]
5-FU	IHC	945	Not significant	CRC	Soong et al[107]
5-FU/LV	RT-PCR	33	Low expression	aCRC	Salonga et al[17]
5-FU/LV/CPT-11	RT-PCR	13	Not significant	aCRC	Yanagisawa et al[37]
Capecitabine	RT-PCR	37	Not significant	aCRC	Vallböhmer et al[97]
Capecitabine/OX	IHC	41	High expression	mCRC	Petrioli et al[448]
Capecitabine/CPT-11	RT-PCR	67	High expression	aCRC	Meropol et al[98]
Capecitabine/CPT-11	IHC	556	Not significant	aCRC	Koopman et al[110]
5-FU-based therapy	RT-PCR	144	Low expression	aCRC	Gustavsson et al[446]
5-FU-based therapy	IHC	150	Low expression	aCRC	Tokunaga et al[447]
Uridine monophosphate synthetase (UMPS) (OMIM #613891)
5-FU	RT-PCR	38	Not significant	mCRC	Sameshima et al[449]
5-FU	RT-PCR	39	Not significant	CRC	Ishida et al[25]
5-FU/LV/OX	RT-PCR	58	Not significant	CRC	Dong et al[450]
5-FU/LV/cisplatin	RT-PCR	22	High expression	mCRC	Matsuyama et al[113]
UFT	RIA	40	High expression	CRC	Ichikawa et al[114]
UFT	RIA	124	High expression	CRC	Ochiai et al[115]
UFT	IHC	150	High expression	CRC	Tokunaga et al[116]
UFT	IHC	160	High expression	CRC	Tokunaga et al[117]
UFT/LV	RT-PCR	37	High expression	mCRC	Ichikawa et al[118]
UFT/LV	RT-PCR	103	High expression	CRC	Yamada et al[119]
5-FU-based therapy	RT-PCR	10	Not significant	CRC	Ishibashi et al[451]
5-FU-based therapy	RIA	11	Not significant	CRC	Yamada et al[452]
5-FU-based therapy	RT-PCR	52	Not significant	CRC	Kinoshita et al[453]
5-FU-based therapy	RIA	54	High expression	CRC	Fujii et al[120]
5-FU-based therapy	RIA	90	High expression	CRC	Ochiai et al[121]

5-FU: 5-fluorouracil; LV: Leucovorin; FUdR: 5-fluorodeoxyuridine; MTX: Methotrexate; OX: Oxaliplatin; UFT: Compound tegafur tablets; CPT-11: Irinotecan; CTX: Cetuximab; RT-PCR: Reverse trascriptase polymerase chain reaction; IHC: Immunohistochemistry; ELISA: Enzyme-linked immunosorbent ssay; RIA: Radioimmunoassay; CRC: Colorectal cancer; aCRC: Advanced colorectal cancer; mCRC: Metastatic colorectal cancer.

Table 3 Selected common polymorphisms of UGT1A1, UGT1A7, UGT1A9, CES2, CYP3A4, CYP3A5, MDR1, MRP1, MRP2, BCRP, OATP1B1 genes and their potential impact on functioning of proteins related to CPT-11 pharmacology

dbSNP rs cluster ID	Type of polymorphism	Function	Ref.
UDP-glycosyltransferase 1A1 (UGT1A1) (OMIM # 191740)
rs8175347	VNTR		[177,178,180,182,191,192,197,219,317,356,454-460]
	-53(TA)6>7	UGT1A1*28, reduced activity
	-53(TA)6>5	UGT1A1*36, increased activity
	-53(TA)6>8	UGT1A1*37, reduced activity
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 8175347
rs3755319	SNP		[187]
	-3279T>G	UGT1A1*60, reduced activity
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 3755319
rs10929302a	SNP		[192,404]
	-3156G>A	UGT1A1*93, reduced activity
rs887829b	-3140G>A	effect unknown
ahttp://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 10929302
bhttp://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 887829
rs4148323	SNP		[186,191,461]
	211G>A	Gly71Arg, UGT1A1*6, reduced activity
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 4148323
rs35350960	SNP		[172,174,189]
	686C>A	Pro229Gln, UGT1A1*27, reduced activity
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 35350960
rs34993780	SNP		[170,174,189]
	1456T>G	Tyr486Asp, UGT1A1*7, reduced activity
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 34993780
UDP-glycosyltransferase 1A7 (UGT1A7) (OMIM #606432)
rs17868323a	SNP		[188,189,197,237]
	387T>G	Asn129Lys, UGT1A7*2 and *3, increased activity
rs17863778b	391C>A	Arg131Lys, UGT1A7*2 and *3, increased activity
rs11692021c	622C>T	Trp208Arg, UGT1A7*3 and *4, reduced activity
ahttp://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 17868323
bhttp://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 17863778
chttp://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 11692021
UDP-glycosyltransferase 1A9 (UGT1A9) (OMIM #606434)
rs45625337	VNTR		[190,197,462]
	–118(T)9>10	UGT1A9*22, increased activity
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 45625337
rs2741049	SNP		[197,463]
	IVS1+399C>T	Effect unknown
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 2741049
Carboxylesterase 2 (CES2) (OMIM #605278)
-	SNP		[159,161,166]
	1A>T	Met1Leu, CES*5
rs72547531a	100C>T	Arg98Trp, CES*2
rs72547532b	424G>A	Val206Met, CES*3
rs8192924c	617G>A	Arg270His, CES*6
rs11075646d	830C>G	Synonymous
rs72547533e	IVS8-2A>G	Splicing defect, CES*4
ahttp://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 72547531
bhttp://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 72547532
chttp://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 8192924
dhttp://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 11075646
ehttp://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 72547533
Cytochrome P450, subfamily IIIA, polypeptide 4 (CYP3A4) (OMIM #124010)
rs2740574a	SNP		[211,464,465]
	-392A>G	CYP3A4*1b, altered pharmacokinetics and toxicity
rs4986907b	485G>A	CYP3A4*15, Arg162Gln
rs4986908c	520G>C	CYP3A4*10, Asp174His
rs12721627d	554C>G	CYP3A4*16, Thr185Ser
rs4987161e	566T>C	CYP3A4*17, Phe189Ser, altered pharmacokinetics
rs55785340f	664T>C	CYP3A4*2, Ser222Pro, altered pharmacokinetics and toxicity
rs28371759g	878T>C	CYP3A4*18, Leu293Pro, altered pharmacokinetics and toxicity
ahttp://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 2740574
bhttp://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 4986907
chttp://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 4986908
dhttp://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 12721627
ehttp://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 4987161
fhttp://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 55785340
ghttp://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 28371759
rs4986910	SNP		[210,465]
	1334T>C	CYP3A4*3, Met444Thr
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 4986910
Cytochrome P450, subfamily IIIA, polypeptide 5 (CYP3A5) (OMIM #605325)
rs776746	SNP		[179,464-467]
	6986A>G	Synonymous
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 776746
Multidrug resistance 1 (MDR1, ABCB1) (OMIM #171050)
rs1128503	SNP		[210,211,217,460,467-469]
	1236C>T	Synonymous, CTP-11 or SN-38 AUC ↑
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 1128503
rs2032582	SNP		[217,468-470]
	2677G>T/A	Ser893Ala or Ser893Thr
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 2032582
rs1045642	SNP		[179,217,468-475]
	3435C>T	Synonymous, CTP-11 AUC ↑
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 1045642
rs10276036	SNP		[207]
	IVS9-44A>G	Effect unknown
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 10276036
Multidrug resistance-associated protein 1 (MRP1, ABCC1) (OMIM #158343)
rs35605	SNP		[210,476]
	1684T>C	Synonymous
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 35605
rs17287570	SNP		[237]
	c.1677+4951A>C	Effect unknown
rs3765129	SNP		[207,210,476]
	IVS11-48C>T	Effect unknown
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 3765129
rs2074087	SNP		[476,477]
	IVC18-30C>G	Effect unknown
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 2074087
Multidrug resistance-associated protein 2 (MRP2, ABCC2) (OMIM #601107)
rs1885301	SNP		[477]
	-1549A>G	Effect unknown
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 1885301
rs2804402	SNP		[207]
	-1019A>G	Effect unknown
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 2804402
rs717620	SNP		[477-479]
	-24C>T	Effect unknown
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 717620
rs2273697	SNP		[467,479,480]
	1249G>A	Val417Ile, effect unknown
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 2273697
rs3740066	SNP		[477,479,481]
	3972C>T	Synonymous, CTP-11 or APC or SN-38G AUC ↑
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 3740066
Breast cancer resistance protein (BCRP, ABCG2) (OMIM #603756)
rs2622604a	SNP		[237]
	c.-19-17758A>G	Synonymous
rs3109823b	c.-19-3436G>A	Synonymous
ahttp://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 2622604
bhttp://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 3109823
rs2231142	SNP		[239-244,482]
	421C>A	Gln141Lys, no significant changes in CPT-11 pharmacokinetics
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 2231142
rs2231137	SNP		[242,467,482]
	34G>A	Val12Met, higher drug resistance in vitro (SN-38)
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 2231137
rs1481012	SNP		[483]
	c.841+179T>C	Synonymous
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 1481012
Organic anion-transporting polypeptide 1B1 (OATP1B1, SLCO1B1) (OMIM #604843)
rs2306283	SNP		[247-249,460,467,484]
	388A>G	Asn130Asp, effect unknown
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 2306283
rs4149056	SNP		[247-249,460]
	521T>C	Val174Ala, effect unknown
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 4149056

SNP: Single nucleotide polymorphism.

Table 4 Selected common polymorphisms of MDR1, GSTP1, ERCC1, ERCC2, XRCC1 genes and their potential impact on functioning of proteins related to OX pharmacology

dbSNP rs cluster ID	Type of polymorphism	Function	Ref.
Multidrug resistance 1 (MDR1, ABCB1) (OMIM #171050)
rs1128503	SNP		[152,296,318,485]
	1236C>T	Synonymous, effect unknown
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 1128503
rs2032582	SNP		[152,296]
	2677G>T/A	Ser893Ala or Ser893Thr, the GG genotype carriers have the highest while the AT genotype carriers have the lowest levels of ABCB1 expression
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 2032582
rs1045642	SNP		[152,296,350,485]
	3435C>T	Synonymous, TT genotype carriers have lower intestinal ABCB1 expression
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 1045642
Glutathione S-transferase π (GSTP1) (OMIM #134660)
rs1138272	SNP		[311,477]
	341C>T	Ala114Val, altered enzyme kinetics, altered toxicity
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 1138272
rs1695	SNP		[51,180,311-329,467,477]
	313A>G	Ile105Val, decreased enzymatic activity, altered toxicity
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 1695
Excision repair cross-complementation group 1 (ERCC1) (OMIM #126380)
rs11615	SNP		[51,313,344,345,357,486]
	354T>C	Synonymous, decreased transcriptional activity of ERCC1
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 11615
rs3212948	SNP		[487]
	321+74C>G	Intronic SNP (intron 2), protective effect of the C allele to cancer risk
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 3212948
Excision repair cross-complementation group 2 (ERCC2, XPD) (OMIM #126340)
rs13181	SNP		[51,313,336,337,350,351,353,356,357,486]
	2251A>C	Lys751Gln, the Gln allele is associated with a higher DNA adduct level or lower DNA repair capacity
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 13181
rs1799793	SNP		[313,336,337,353]
	862G>A	Asp312Asn, lower DNA repair capacity for the Asn allele than the Asp allele
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 1799793
X-ray cross complementation factor (XRCC1) (OMIM #194360)
rs25487	SNP		[51,313,349,350,361-364,486]
	1196A>G	Arg399Gln, reduced base excision repair function for Gln allele than the Arg allele
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs = 25487

SNP: Single nucleotide polymorphism.