ABCMdb

PMID: 20602618

Marsh S, Hoskins JM
Irinotecan pharmacogenomics.
Pharmacogenomics. 2010 Jul;11(7):1003-10., [PubMed]

Sentences

No. Mutations Sentence Comment

36 ABCG2 p.Gln141Lys ABCB1 1236C>T rs1128503 Decreased irinotecan clearance; risk of toxicity and reduced survival when in haplotype with 2677 and 3435 [56,58,59] ABCB1 2677G>A/T rs2032582 Risk of toxicity and reduced survival when in haplotype with 1236 and 3435 [58,59] ABCB1 3435C>T rs1045642 Increased toxicity; risk of toxicity and reduced survival when in haplotype with 1236 and 2677 [57-59] ABCC2 -24C>T rs717620 Increased response and survival with 3972; toxicity as part of ABCC2 haplotype in patients without GT1A1*28 [46,61-63] ABCC2 3972T>C rs3740066 Increased response and survival with -24; toxicity as part of ABCC2 haplotype in patients without UGT1A1*28 [43,46,60-63] ABCG2 34G>A rs2231137 Increased toxicity; no association with toxicity and outcome [60,61] ABCG2 421C>A; Q141K rs2231142 Reduced expression; irinotecan resistance; toxicity with IVS12 +49G>T [49,61,66,67] ABCG2 IVS12+49G>T rs3832043 Toxicity with 421C>A [49,61,66,67] CES1 -816A>C Unknown Altered CES1 promoter activity [22] CES2 830C>G; -171C>G rs11075646 No association with expression, catalytic activity, toxicity or outcome [20] CYP3A4 Activity Altered irinotecan dosing requirement [24] NR1I2 Expression Altered SN-38 glucuronidation [79] TDP1 IVS12+79T>G rs2401863 Response; no toxicity association at higher doses [74,75] UGT1A1 -3156G>A rs10929302 Increased risk of toxicity [32,33] UGT1A1 (TA)7 TAA, *28 rs8175347 Increased risk of toxicity; dose dependent [32,33,38-41] UGT1A1 G71R, *6 rs4148323 Increased risk of toxicity [44,47] UGT1A7 *2 (N129K and R131K) rs17868323, rs17868324 SN-38 glucuronidation; response [47,52] UGT1A7 *3 (N129K, R131K and W208R) rs17868323, rs17868324, rs11692021 SN-38 glucuronidation; increased risk of toxicity; altered response [47,52,54] UGT1A9 -118(dT) rs3832043 SN-30 glucuronidation; response [44,47,52,54] XRCC1 Haplotype (-1149delGGCC, R399Q) rs321329 rs25487 Response [74] XRCC1 R399Q rs25487 No association with toxicity; association with response [76,77] dbSNP: SNP database Asians to 45% in Africans. Login to comment 77 ABCG2 p.Gln141Lys The ABCG2 variant 421C>A (Q141K) reduced ABCG2 gene expression and caused irinotecan resistance in cancer cell lines [66] and neutropenia in 55 patients receiving irinotecan monotherapy when assessed as a haplotype with ABCG2 IVS12 +49G>T [67]. Login to comment 268 ABCG2 p.Gln141Lys 66 Imai Y, Nakane M, Kage K et al.: C421A polymorphism in the human breast cancer resistance protein gene is associated with low expression of Q141K protein and low-level drug resistance. Login to comment