ABCC2 p.Lys757Glu
| Predicted by SNAP2: | A: D (71%), C: D (66%), D: D (85%), E: D (80%), F: D (75%), G: D (80%), H: D (63%), I: D (71%), L: D (71%), M: D (66%), N: D (66%), P: D (85%), Q: D (63%), R: N (82%), S: D (71%), T: D (75%), V: D (66%), W: D (80%), Y: D (75%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: D, L: D, M: D, N: D, P: D, Q: D, R: N, S: D, T: D, V: D, W: D, Y: D, |
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[hide] Association study of genetic polymorphism in ABCC4... J Hum Genet. 2009 Oct;54(10):564-71. Epub 2009 Aug 21. 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., [PMID:19696793]
Abstract [show]
Cyclophosphamide (CPA)-based combination treatment has known to be effective for breast cancer, but often causes adverse drug reactions (ADRs). Hence, the identification of patients at risk for toxicity by CPA is clinically significant. In this study, a stepwise case-control association study was conducted using 403 patients with breast cancer who received the CPA combination therapy. A total of 143 genetic polymorphisms in 13 candidate genes (CYP2B6, CYP2C9, CYP2C19, CYP3A4, CYP3A5, ALDH1A1, ALDH3A1, GSTA1, GSTM1, GSTP1, GSTT1, ABCC2 and ABCC4), possibly involved in the activation, metabolism and transport of CPA, were genotyped using 184 cases who developed either > or =grade 3 leukopenia/neutropenia or > or =grade 2 gastrointestinal toxicity and 219 controls who did not show any ADRs throughout the treatment. The association study revealed that one SNP, rs9561778 in ABCC4, showed a significant association with CPA-induced ADRs (Cochran-Armitage trend's P-value=0.00031; odds ratio (OR)=2.06). Subgroup analysis also indicated that the SNP rs9561778 was significantly associated with two major ADR subgroups; gastrointestinal toxicity and leukopenia/neutropenia (Cochran-Armitage trend's P-value=0.00019 and 0.014; OR=2.31 and 1.83). Furthermore, the SNP rs9561778 showed an association with breast cancer patients who were treated with CA(F) drug regimen-induced ADR (Cochran-Armitage trend's P-value=0.00028; OR=3.13). The SNPs in ABCC4 might be applicable in predicting the risk of ADRs in patients receiving CPA combination chemotherapy.
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53 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).
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ABCC2 p.Lys757Glu 19696793:53:3815
status: NEW