ABCMdb

PMID: 19696793

Low SK, Kiyotani K, Mushiroda T, Daigo Y, Nakamura Y, Zembutsu H
Association study of genetic polymorphism in ABCC4 with cyclophosphamide-induced adverse drug reactions in breast cancer patients.
J Hum Genet. 2009 Oct;54(10):564-71. Epub 2009 Aug 21., [PubMed]

Sentences

No. Mutations Sentence Comment

53 ABCC2 p.Ser185Thr ABCC2 p.Lys757Glu This subgroup analysis revealed that the SNP rs9561778 in ABCC4 Table 1 Patients` characteristics Case (ADR) Control (non-ADR) The number of samples First set 76 140 Second set 108 79 Total 184 219 Mean age at diagnosis 57.7 52.0 Types of adverse drug reaction ^Grade 3 leucopenia or neutropenia 91 219 ^Grade 2 gastrointestinal toxicity 118 219 Table 2 Relationship between single nucleotide polymorphisms (SNPs) in candidate genes and ADR risk induced by CPA combination therapy MAF Cochran-Armitage HWE CHR Gene SNP Allele1 Allele2 Position/effect ADR Non-ADR trend P-value ADR Non-ADR 6 GSTA rs9367495 C T 3' UTR GSTA1 0.16 0.09 0.059 0.38 1.00 6 rs9395826 G A 3' UTR GSTA5 0.34 0.29 0.26 0.61 0.53 6 rs7739421 A G Intron 6 of GSTA5 0.18 0.20 0.68 0.71 0.79 6 rs9370155 G C Intron 5 of GSTA5 0.16 0.19 0.44 0.68 0.41 7 CYP3A5 rs776746 T C Intron_3 0.24 0.22 0.64 1.00 0.62 7 CYP3A4 rs28371759 C T Pro293Leu 0.03 0.01 0.22 1.00 1.00 7 rs12721627 G C Ser185Thr 0.02 0.00 0.092 1.00 1.00 9 ALDH1A1 rs4646548 G A 3' UTR 0.46 0.40 0.20 0.47 0.72 9 rs348471 G A Intron 12 0.48 0.42 0.26 0.36 0.86 9 rs1330291 T C Intron 11 0.08 0.10 0.66 1.00 0.62 9 rs4646544 C A Intron 7 0.09 0.10 0.65 0.08 1.00 9 rs8187929 A T Phe177Ile 0.03 0.04 0.72 1.00 1.00 9 rs13959 T C Exon 3 syn. 0.45 0.43 0.61 0.50 0.22 9 rs647880 A G Intron 1 0.46 0.49 0.60 0.16 0.50 9 rs10156653 T C Intergenic 0.46 0.50 0.47 0.64 0.24 9 rs3003989 C T Intergenic 0.05 0.03 0.47 0.14 1.00 9 rs7853400 G A Intergenic 0.38 0.42 0.41 0.81 0.49 10 CYP2C9 rs1074145 A G Intergenic 0.29 0.25 0.35 0.26 0.021 10 rs10509679 A G Intron 4 0.32 0.28 0.42 0.19 0.10 10 rs4918766 A G Intron 5 0.54 0.44 0.045 0.25 0.50 10 rs1057910 C A Tyr358Leu 0.05 0.05 0.99 1.00 1.00 10 rs1934968 T C Intron 7 0.22 0.30 0.057 0.74 1.00 10 rs11188133 G A 5' UTR 0.44 0.51 0.15 0.82 0.31 10 CYP2C19 rs4986893 A G Ter212Trp 0.18 0.13 0.20 1.00 1.00 10 rs4244285 A G Exon 5 syn. 0.31 0.26 0.26 0.29 0.045 10 ABCC2 rs2804398 T A Intron 7 0.14 0.12 0.59 0.62 0.41 10 rs2756109 T G Intron 7 0.36 0.34 0.80 0.13 0.19 10 rs11190291 T C Intron 11 0.14 0.14 0.99 0.34 0.14 10 rs2002042 T C Intron 19 0.31 0.32 0.92 0.03 0.17 10 rs3740065 G A Intron 29 0.35 0.36 0.91 0.80 0.14 10 rs12762549 C G Intergenic 0.42 0.44 0.76 0.35 0.010 10 rs2862691 T C Intergenic 0.23 0.21 0.65 1.00 0.44 11 GSTP1 rs612020 T C Intergenic 0.20 0.20 0.86 0.47 1.00 11 rs614080 G A 5' UTR 0.38 0.35 0.55 0.47 0.57 11 rs1695 G A Val105Ile 0.17 0.14 0.35 0.44 0.72 13 ABCC4 rs4148542 G A Intron 30 0.50 0.48 0.67 0.06 0.50 13 rs9561765 A G Intron 30 0.27 0.27 0.99 0.39 0.28 13 rs6492763 T C Intron 30 0.46 0.51 0.35 0.37 0.31 13 rs2182262 T C Intron 29 0.26 0.23 0.43 0.37 1.00 13 rs4148540 T C Intron 29 0.24 0.28 0.41 0.76 0.30 13 rs1614102 A G Intron 26 0.30 0.21 0.037 0.42 0.44 13 rs1751031 G A Intron 26 0.28 0.33 0.28 0.39 0.08 13 rs9561778 T G Intron 26 0.24 0.13 0.0086 0.75 0.71 13 rs931110 G A Intron 26 0.53 0.47 0.29 0.65 0.12 13 rs4148532 T A Intron 21 0.22 0.14 0.032 1.00 0.73 13 rs17234998 T C Intron 20 0.16 0.21 0.22 0.19 0.015 13 rs1751055 T C Intron 20 0.28 0.34 0.23 0.78 0.19 13 rs2698243 C T Intron 20 0.47 0.51 0.39 0.36 0.17 13 rs1729775 A G Intron 20 0.28 0.18 0.027 1.00 1.00 2 Continued MAF Cochran-Armitage HWE CHR Gene SNP Allele1 Allele2 Position/effect ADR Non-ADR trend P-value ADR Non-ADR 13 rs9561784 G A Intron 20 0.19 0.21 0.64 0.45 0.19 13 rs1729741 G A Intron 19 0.13 0.18 0.23 1.00 0.57 13 rs1751070 G C Intron 19 0.23 0.15 0.029 0.33 0.31 13 rs2619313 T C Intron 19 0.24 0.23 0.78 0.03 0.46 13 rs997777 T A Intron 19 0.38 0.39 0.85 0.15 0.48 13 rs4148508 T A Intron 19 0.16 0.15 0.64 0.68 0.17 13 rs1479390 A C Intron 19 0.27 0.31 0.34 1.00 0.84 13 rs7988595 C A Intron 19 0.19 0.27 0.057 1.00 0.83 13 rs7988271 T C Intron 19 0.10 0.16 0.10 0.54 0.75 13 rs3765534 T C Lys757Glu 0.11 0.17 0.14 1.00 0.54 13 rs1729764 G A Intron 16 0.33 0.32 0.93 1.00 0.85 13 rs4148500 T C Intron 15 0.21 0.19 0.57 0.30 0.41 13 rs9561797 G A Intron 14 0.28 0.36 0.080 0.57 0.26 13 rs12429339 A T Intron 14 0.16 0.17 0.70 0.38 1.00 13 rs1729786 A G Intron 13 0.30 0.23 0.12 0.42 0.34 13 rs1189458 C T Intron 13 0.31 0.37 0.24 0.79 0.46 13 rs6492768 G A Intron 13 0.48 0.46 0.69 0.50 1.00 13 rs1751003 A G Intron 13 0.15 0.16 0.88 0.67 0.74 13 rs1887162 T G Intron 13 0.22 0.27 0.31 0.51 0.67 13 rs10161985 T C Intron 11 0.45 0.43 0.66 0.16 0.39 13 rs1564352 T G Intron 11 0.33 0.35 0.80 1.00 0.71 13 rs10162199 T C Intron 11 0.33 0.30 0.61 1.00 0.69 13 rs3843689 G A Intron 11 0.29 0.30 0.81 0.58 0.84 13 rs2766474 A G Intron 11 0.15 0.16 0.76 0.65 0.75 13 rs1557069 G A Intron 10 0.24 0.22 0.76 1.00 0.47 13 rs4773843 T C Intron 10 0.13 0.15 0.59 1.00 1.00 13 rs9561802 A G Intron 10 0.17 0.15 0.61 1.00 0.74 13 rs1678374 T C Intron 9 0.41 0.40 0.96 1.00 0.28 13 rs4148486 T C Intron 9 0.33 0.33 0.95 0.43 0.70 13 rs7319330 C T Intron 9 0.47 0.50 0.65 1.00 0.73 13 rs4148481 C T Intron 9 0.40 0.41 0.88 1.00 0.59 13 rs1678384 A G Intron 8 0.05 0.07 0.63 1.00 0.012 13 rs4148478 C T Intron 8 0.29 0.31 0.67 0.58 0.55 13 rs1751022 T C Intron 8 0.24 0.21 0.52 0.11 0.61 13 rs1751025 G C Intron 8 0.30 0.29 0.78 1.00 0.83 13 rs4773844 T C Intron 8 0.27 0.29 0.79 0.24 0.53 13 rs17268170 T C Intron 8 0.07 0.07 0.81 1.00 1.00 13 rs9556465 T G Intron 8 0.07 0.09 0.41 1.00 0.60 13 rs1751029 A G Intron 8 0.19 0.18 0.78 0.06 0.25 13 rs2274408 T C Intron 7 0.45 0.42 0.54 0.65 0.22 13 rs9524827 C T Intron 6 0.38 0.37 0.87 0.32 0.71 13 rs873706 T C Intron 5 0.37 0.37 0.95 0.63 0.35 13 rs11568658 T G Trp187Gly 0.07 0.10 0.43 0.33 0.61 13 rs9524831 C A Intron 4 0.26 0.28 0.75 0.37 0.52 13 rs7330519 T C Intron 4 0.49 0.50 0.84 0.35 0.49 13 rs4773856 A G Intron 4 0.22 0.22 0.98 0.75 1.00 13 rs9561814 C T Intron 4 0.17 0.18 0.82 0.03 0.77 13 rs7333234 A G Intron 4 0.32 0.34 0.79 0.43 0.70 13 rs4148456 G A Intron 3 0.09 0.09 0.94 1.00 1.00 13 rs9561817 T C Intron 3 0.37 0.38 0.89 0.32 0.58 13 rs4258481 C G Intron 3 0.51 0.49 0.69 0.10 0.86 13 rs12427972 A G Intron 3 0.28 0.32 0.42 0.24 0.69 13 rs2892715 A G Intron 3 0.16 0.11 0.14 0.0022 1.00 13 rs4148450 G A Intron 3 0.28 0.32 0.39 0.26 0.84 13 rs10508019 T C Intron 3 0.22 0.28 0.23 0.33 0.67 13 rs4148440 A G Intron 3 0.45 0.47 0.71 0.35 0.12 13 rs4148436 C T Intron 2 0.27 0.22 0.30 0.37 0.80 13 rs4148434 A G Intron 1 0.20 0.16 0.33 0.06 0.34 showed a significant association with a higher odds ratio (Cochran-Armitage trend`s P-value¼0.00028; OR¼3.13; 95% CI¼1.68-5.83) with patients treated with the CA(F) regimen (Table 5). Login to comment 56 ABCC4 p.Arg262Lys ABCC4 p.His172Gln ABCC4 p.Ala134Ser In this study, we examined a total of 141 SNPs and two gene deletions in 13 candidate genes that were considered to be involved in the activation (CYP2B6, CYP2C9, Table 2 Continued MAF Cochran-Armitage HWE CHR Gene SNP Allele1 Allele2 Position/effect ADR Non-ADR trend P-value ADR Non-ADR 13 rs9590216 T C Intron 1 0.45 0.46 0.93 0.24 0.11 13 rs9561820 T C Intron 1 0.31 0.29 0.63 0.17 0.010 13 rs4148431 A G Intron 1 0.44 0.45 0.84 0.48 0.023 13 rs7328332 T C Intron 1 0.14 0.10 0.23 1.00 1.00 13 rs870004 A G Intron 1 0.18 0.26 0.063 0.69 0.65 13 rs8001475 C T Intron 1 0.29 0.35 0.24 0.78 0.45 13 rs4148426 G C Intron 1 0.18 0.25 0.11 0.68 0.34 13 rs9524873 A G Intron 1 0.26 0.22 0.40 0.25 0.010 13 rs4771910 C T Intron 1 0.30 0.35 0.40 0.58 0.70 13 rs10508017 T C Intron 1 0.24 0.23 0.83 0.34 0.025 13 rs4148424 T C Intron 1 0.34 0.36 0.56 0.61 1.00 13 rs4148422 C T Intron 1 0.37 0.36 0.92 0.80 0.26 13 rs34665760 A G Intron 1 0.24 0.30 0.21 0.75 0.84 13 rs4773872 T C Intron 1 0.28 0.36 0.084 0.40 0.57 13 rs4771912 G A Intron 1 0.24 0.33 0.045 1.00 0.33 13 rs4773875 T G Intron 1 0.43 0.35 0.10 0.34 0.70 13 rs8001444 T C Intron 1 0.37 0.47 0.041 0.80 1.00 17 ALDH3A1 rs758427 T C 5' near gene 0.49 0.49 0.88 0.82 0.73 17 rs11657205 T C 5' near gene 0.49 0.48 0.82 1.00 0.49 17 rs11204411 C T 5' near gene 0.20 0.22 0.67 1.00 0.45 17 rs57555435 A G Exon 10 syn. 0.14 0.14 0.85 0.34 0.040 17 rs2228100 G C Ala329Pro 0.32 0.33 0.82 1.00 0.85 17 rs3744692 A G Glu309Gly 0.03 0.05 0.36 1.00 1.00 17 rs2072330 A T Exon 6 syn. 0.45 0.44 0.83 0.64 0.06 17 rs887241 T G Ala134Ser 0.03 0.04 0.73 1.00 1.00 19 CYP2B6 rs7254579 C T 5' near gene 0.46 0.49 0.57 0.24 0.24 19 rs4802101 T C 5' near gene 0.39 0.32 0.17 0.81 0.56 19 rs4803415 T C Intron 1 0.23 0.19 0.35 0.52 0.28 19 rs4803419 T C Intron 3 0.45 0.49 0.49 0.64 0.61 19 rs3745274 T G His172Gln 0.13 0.17 0.32 1.00 1.00 19 rs2279343 G A Arg262Lys 0.16 0.22 0.13 1.00 0.81 19 rs2279345 T C Intron 5 0.36 0.31 0.28 1.00 0.32 19 rs7255374 T C Intron 8 0.19 0.22 0.51 1.00 0.80 19 rs1042389 C T 3' UTR 0.30 0.26 0.46 0.09 0.83 GSTM1 and GSTT1 deletion ADR Non-ADR Gene Deletion Wildtype Deletion Wildtype Fisher`s exact P-value Odds ratio GSTM deletion 46 51 102 87 0.32 0.769 GSTT deletion 41 56 83 108 0.90 0.953 Abbreviations: ADR, adverse drug reaction; HWE, Hardy-Weinberg equilibrium; MAF, minor allele frequency. 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