FOLFOX/FOLFIRI pharmacogenetics: The call for a personalized approach in colorectal cancer therapy

Table 1 Putative biomarkers of efficacy and/or toxicity of 5-fluorouracil in colorectal cancer

Gene	Transcript	Protein	SNP	Effect	Ref.
SLC29A1	-	High	-	Inferior clinical response	Phua et al[40] 2013
ABCC11	Low	-	-	Inferior response and shorter DFS	Hlavata et al[28] 2012
TYMP	High	High	-	Longer DFS and OS	Meropol et al[48] 2006
		High	-	Better clinical response	Sadahiro et al[51] 2012
	-	High cytoplasmic	-	Longer OS	Mitselou et al[52] 2012
	High	-	-	pCR	Chiorean et al[50] 2012
	-	No association	-	DFS and OS	Ciaparrone et al[42] 2006
	No association	-	-	OS	Lassmann et al[43] 2006
	-	No association	-	OS	Soong et al[44] 2008
	No association	-	-	Clinical response	Vallbohmer et al[45] 2007
	No association	-	-	PFS and OS	Koopman et al[49] 2009
UMPS	No association	-	-	Longer OS	Yanagisawa et al[54] 2007
	-	High	-	Longer OS	Tokunaga et al[55] 2007
	-	High (tumor cells)	-	Shorter OS	Koopman et al[56] 2009
	-	High (stromal cells)	-	Longer OS	Koopman et al[56] 2009
DPYD	Low	-	-	Longer OS	Yanagisawa et al[54] 2007
	Low	-	-	Longer OS	Vallböhmer et al[45] 2007
	-	Low	-	Longer OS	Tokunaga et al[55] 2007
	-	Low1	-	Longer OS1	Koopman et al[56] 2009
	-	Low	-	Longer OS	Ciaparrone et al[42] 2007
	-	No association	-	DFS	Westra et al[59] 2005
	-	-	Rs3918290	Higher toxicity	Caudle et al[27] 2013
				Dose reduction recommended	Swen et al[62] 2011
	-	-	Rs55886062	Higher toxicity	Caudle et al[27] 2013
				Dose reduction recommended	Swen et al[62] 2011
	-	-	Rs67376798	Higher toxicity	Caudle et al[27] 2013
				Dose reduction recommended	Swen et al[62] 2011
TYMS	-	No association	-	Clinical response	Jennings et al[57] 2012
	-	-	Rs45445694	Lower protein expression, clinical benefit and higher toxicity improved	Jennings et al[57] 2012

¹Only when combined with irinotecan. PFS: Progression-free survival; DFS: Disease-free survival; OS: Overall survival; pCR: Complete pathological response.

Table 2 Putative biomarkers of efficacy and/or toxicity of oxaliplatin in colorectal cancer

Gene	Transcript	Protein	SNP	Effect	Ref.
ATP7B	Low	Low	-	Longer PFS	Martinez-Balibrea et al[78] 2009
ABCB1	No association	-	-	DFS and OS	Hlavata et al[28] 2012
	-	-	AG genotype in rs1045642	Longer DFS	Wu et al[79] 2013
	-	-	AA genotype in rs1128503	Longer OS	Wu et al[79] 2013
	-	-	AA-GG-TT haplotype in rs1045642-rs1128503-rs2032582	Shorter PFS and OS	Wu et al[79] 2013
ERCC1	High	-	-	Shorter OS	Shirota et al[80] 2001
	High	-	-	Shorter OS	Grimminger et al[81] 2011
	-	High	-	Shorter DFS and OS	Huang et al[82] 2013
	-	No association	-	PFS and OS	Koopman et al[49] 2009
	-	-	GG genotype in rs11615	Longer OS	Huang et al[83] 2011
	-	-	Rs11615	No association with OS	Martinez-Balibrea et al[84] 2011
ERCC2	-	No association		DFS and OS	Huang et al[110] 2013
	-	-	Variant allele in rs1052559	Shorter OS	Le Morvan et al[86] 2007
XRCC1	-	No association		DFS and OS	Huang et al[82] 2013
	-	-	CC genotype in rs25487	Longer OS	Huang et al[83] 2011
GSTM1 deletion	-	-	One copy	Longer OS	Funke et al[87] 2010
	-	-	Null genotype	Higher neutropenia	McLeod et al[90] 2010
GSTP1	-	-	AA genotype in rs1695	Inferior response	Kumamoto et al[88] 2013
	-	-	Rs1695	No association	Funke et al[87] 2010
	-	-	Rs1695	No association	Huang et al[85] 2008
	-	-	Rs1695	No association	Le Morvan et al[86] 2011
	-	-	AA genotype in rs1695	Higher neurotoxicity	McLeod et al[90] 2010
	-	-	Rs1695	No association with toxicity	Peng et al[91] 2013
GSTT1	-	-	Deletion	No association	Funke et al[87] 2010
	-	-	Deletion	No association	Huang et al[85] 2008
	-	-	Deletion	No association	Le Morvan et al[86] 2011

PFS: Progression-free survival; DFS: Disease free survival; OS: Overall survival.

Table 3 Putative biomarkers of efficacy and/or toxicity of irinotecan in colorectal cancer

Gene	Transcript	Protein	SNP	Effect	Ref.
ABCB1	-	-	rs11288503	Decreased clearance of irinotecan	Mathijssen et al[103] 2003
ABCB1	-	-	rs112503T-rs2032582T-rs1045642T haplotype	Higher levels of SN-38	Sai et al[104] 2010
	-	-	rs112503T-rs2032582T-rs1045642T haplotype	Shorter OS	Glimelius et al[106] 2010
ABCG2	-	-	rs7699188	Associate with RR	De Mattia et al[105] 2013
	-	-	GG genotype in rs425215	Higher GI toxicity	Di Martino et al[117] 2011
ABCC2	-	-	CC genotype in rs717620	Longer PFS	Akiyama et al[109] 2012
	-	-	CC genotype in rs562	Higher GI toxicity	Di Martino et al[117] 2011
SLCO1B1	-	-	GA/AA genotype in rs2306283	Higher RR	Huang et al[110] 2013
	-	-	GA genotype in rs 2306283	Lower GI toxicity	Di Martino et al[117] 2011
SLC19A1	-	-	GG genotype in rs1051266	Higher RR	Huang et al[82] 2013
UGT1A1	-	-	28 allele in rs81753471	No association with RR	Dias et al[115] 2012
	-	-	28 allele in rs81753471	Lower RR	Marcuello et al[114] 2011
	-	-	28 allele in rs81753471	Reduced activity of UGT1A1	Swen et al[62] 2011
	-	-	28 allele in rs81753471	Increased toxicity, dose reduction recommended	Swen et al[62] 2011

¹Due to lower tolerated dose. PFS: Progression-free survival; RR: Response rate; OS: Overall survival; GI: Gastrointestinal.