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

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.