ABCMdb

ABCC2 p.Ser185Thr

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Publications

PMID: 19696792 [PubMed] Cha PC et al: "Single nucleotide polymorphism in ABCG2 is associated with irinotecan-induced severe myelosuppression."

No. Sentence Comment

48 In addition to this SNP, rs7977213 in SLCO1B3 as well as the UGT1A7*3 variant Table 1 Demographical characteristic of patients First study Second study Combined study Case (N¼23) Control (N¼58) Case (N¼7) Control (N¼20) Case (N¼30) Control (N¼78) Age 62.04 (37-77) 60.29 (34-77) 60.29 (40-81) 67.60 (50-84) 61.63 (37-81) 62.21 (34-84) % of men 61 71 57 42 60 65 Types of cancers Lung 12 52% 10 17% 2 29% 4 17% 14 47% 14 18% Cervical 6 26% 2 3% 0 0% 0 0% 6 20% 2 3% Colorectal 3 13% 35 60% 3 43% 13 57% 6 20% 48 62% Gastric 1 4% 4 7% 1 14% 2 9% 2 7% 6 8% Ovarian 0 0% 2 3% 1 14% 1 4% 1 3% 3 4% Breast+cervical 1 4% 0 0% 0 0% 0 0% 1 3% 0 0% Pancreatic 0 0% 1 2% 0 0% 0 0% 0 0% 1 1% Esophageal 0 0% 1 2% 0 0% 0 0% 0 0% 1 1% Breast 0 0% 1 2% 0 0% 0 0% 0 0% 1 1% No information 0 0% 2 0% 0 0% 0 0% 0 0% 2 3% Types of regimens CPT-11 1 4% 11 19% 1 14% 2 9% 2 6% 13 17% Other drug combinations 22 96% 47 81% 6 86% 18 91% 28 94% 65 83% Associations of 170 SNPs with severe myelosuppression in subjects who received irinotecan therapy Allele Frequency of allele 1 Fisher test`s P-values Gene name SNP ID Position of SNP/functional SNP 1 2 dCase eControl f1vs2 g11vs h22vs Odds ratio UGT1A9 rs3832043 UGT1A9*1b or *22 9T 10T 0.63 0.63 1.00E+00 8.05EÀ01 7.33EÀ01 0.76 UGT1A7 rs17868323 Exon 1 (Lys 129 Asn) T G 0.54 0.63 3.72EÀ01 1.00E+00 1.16EÀ01 2.68 UGT1A7 1A7_R131Kaa Exon 1 (R131K) (UGT1A7*2) C A 0.54 0.63 3.72EÀ01 1.00E+00 1.16EÀ01 2.68 UGT1A7 1A7_R131Kba Exon 1 (R131K) (UGT1A7*2) G A 0.54 0.63 3.72EÀ01 1.00E+00 1.16EÀ01 2.68 UGT1A7 rs11692021 Exon 1 (Arg 208 Trp) (UGT1A7*3) T C 0.65 0.76 1.71EÀ01 1.00E+00 6.72EÀ03 15.56 UGT1A1 rs887829 Intron (tagged UGT1A1*28, promoter indel) G A 0.96 0.90 3.53EÀ01 1.64EÀ01 1.00E+00 5.15 UGT1A1 rs4148323 Exon 1 (Arg 71 Gly) (UGT1A1*6) G A 0.76 0.78 8.34EÀ01 4.51EÀ01 2.14EÀ02 12.00 UGT1A1 rs35350960 Exon 1 (Gln 229 Pro) (UGT1A1*27) C A 1.00 0.99 1.00E+00 1.00E+00 1.00E+00 NA BCHE rs697356 3' near gene G C 0.30 0.40 2.74EÀ01 4.95EÀ01 4.46EÀ01 1.64 BCHE rs1007845 3' near gene G A 0.83 0.78 6.67EÀ01 6.13EÀ01 1.00E+00 1.40 BCHE rs2048493 Intron 2 C G 0.78 0.62 6.41EÀ02 5.08EÀ02 4.29EÀ01 2.74 BCHE rs4639017 Intron 1 C G 0.72 0.60 2.07EÀ01 2.07EÀ01 7.17EÀ01 2.07 ABCC5 rs6810123 3' near gene A G 0.33 0.41 3.72EÀ01 1.00E+00 2.07EÀ01 2.07 ABCC5 rs12638772 3' near gene A G 0.36 0.32 7.07EÀ01 2.50EÀ01 1.00E+00 2.36 ABCC5 rs7613247 3' near gene A G 0.93 0.94 1.00E+00 1.00E+00 1.00E+00 1.15 ABCC5 rs2176825 3' near gene A G 0.25 0.37 1.81EÀ01 5.07EÀ01 2.07EÀ01 1.98 ABCC5 rs13066518 3' near gene T A 0.33 0.39 4.78EÀ01 1.00E+00 4.50EÀ01 1.62 ABCC5 rs3749443 3' near gene A G 0.20 0.18 1.00E+00 1.00E+00 7.90EÀ01 1.29 ABCC5 rs1402001 3' near gene A G 0.52 0.57 6.03EÀ01 7.95EÀ01 2.30EÀ01 2.10 ABCC5 rs6790814 3' near gene C G 0.66 0.76 2.33EÀ01 4.63EÀ01 1.25EÀ01 4.42 ABCC5 rs9838667 3' near gene T G 0.34 0.46 2.12EÀ01 5.64EÀ01 3.05EÀ01 1.85 ABCC5 rs2280392 3' near gene G A 0.25 0.23 8.35EÀ01 3.40EÀ01 8.02EÀ01 2.84 ABCC5 rs1879257 3' near gene A G 0.43 0.32 2.02EÀ01 3.07EÀ01 3.27EÀ01 2.02 ABCC5 rs3817403 3' near gene A G 0.87 0.90 7.82EÀ01 1.00E+00 1.00E+00 1.19 ABCC5 rs3805111 3' near gene T C 0.09 0.10 7.85EÀ01 1.00E+00 7.72EÀ01 1.24 ABCC5 rs3805108b 3' near gene A G 0.11 0.19 2.50EÀ01 6.69EÀ01 4.00EÀ01 1.97 ABCC5 rs2872247 3' near gene T G 0.76 0.70 4.49EÀ01 6.30EÀ01 6.67EÀ01 1.30 ABCC5 rs2293001 3' near gene T C 0.48 0.54 6.00EÀ01 7.79EÀ01 5.56EÀ01 1.44 ABCC5 rs4148572 Intron 2 C G 0.33 0.22 1.60EÀ01 1.36EÀ01 3.30EÀ01 4.20 ABCC5 rs4148568 Intron 2 A G 0.13 0.18 6.37EÀ01 5.85EÀ01 7.89EÀ01 NA ABCC5 rs4148564 Intron 2 A G 0.89 0.82 3.44EÀ01 3.00EÀ01 1.00E+00 1.89 ABCC5 rs4148560 Intron 2 A T 0.78 0.80 8.30EÀ01 7.96EÀ01 1.36EÀ01 4.20 ABCC5 rs7624838 Intron 2 T C 0.50 0.52 8.63EÀ01 7.82EÀ01 1.00E+00 1.26 ABCG2 rs2231164 Intron 14 C T 0.36 0.39 8.56EÀ01 5.57EÀ02 4.46EÀ01 NA ABCG2 rs2622611 Intron 10 T G 0.16 0.18 8.20EÀ01 3.29EÀ01 1.00E+00 NA ABCG2 rs1871744 Intron 6 T C 0.55 0.69 9.76EÀ02 3.22EÀ01 1.71EÀ01 2.73 ABCG2 rs2231142 Exon 5 (Gln 141 Lys) C A 0.78 0.78 1.00E+00 1.00E+00 1.00E+00 0.79 ABCG2 rs2231137 Exon 2 (Val 12 Met) G A 0.67 0.79 1.53EÀ01 3.19EÀ01 1.36EÀ01 4.20 ABCG2 rs1564481 Intron 1 C T 0.72 0.62 2.77EÀ01 3.15EÀ01 6.67EÀ01 1.74 ABCG2 rs2622624 Intron 1 A G 0.41 0.29 1.93EÀ01 2.78EÀ01 3.35EÀ01 2.41 ABCG2 rs2622604 Intron 1 T C 0.28 0.09 2.35EÀ03 7.81EÀ02 6.66EÀ03 4.40 ABCB1 rs1882478 Intron 27 C T 0.59 0.55 7.27EÀ01 4.31EÀ01 7.57EÀ01 1.57 ABCB1 rs6979885 Intron 27 G A 0.89 0.91 1.00E+00 1.00E+00 1.00E+00 1.19 ABCB1 rs2235047 Intron 27 T G 0.50 0.52 8.63EÀ01 7.82EÀ01 1.00E+00 1.26 ABCB1 rs1045642 Exon 27 (Ile 3 Ile) T C 0.37 0.44 4.80EÀ01 1.00E+00 4.34EÀ01 1.67 ABCB1 rs1002205 Intron 26 C G 0.52 0.60 3.75EÀ01 4.21EÀ01 7.14EÀ01 1.70 ABCB1 rs6949448 Intron 26 T C 0.35 0.40 5.91EÀ01 1.00E+00 6.09EÀ01 1.42 ABCB1 rs2235067 Intron 23 A G 0.07 0.11 5.60EÀ01 1.00E+00 5.36EÀ01 1.83 ABCB1 rs2373588 Intron 22 T C 0.43 0.39 5.98EÀ01 7.20EÀ01 7.99EÀ01 1.53 ABCB1 rs7787082 Intron 22 A G 0.50 0.50 1.00E+00 7.72EÀ01 7.72EÀ01 NA ABCB1 rs3789246 Intron 20 A G 0.09 0.19 1.50EÀ01 5.51EÀ01 2.69EÀ01 2.31 ABCB1 rs1922242b Intron 17 A T 0.78 0.68 2.45EÀ01 3.24EÀ01 4.90EÀ01 1.74 ABCB1 rs2235046 Intron 17 A G 0.72 0.59 1.51EÀ01 4.38EÀ02 1.00E+00 2.89 ABCB1 rs868755 Intron 9 C A 0.59 0.61 1.00E+00 1.00E+00 7.29EÀ01 1.36 ABCB1 rs4148734 Intron 8 C T 0.87 0.90 7.79EÀ01 5.42EÀ01 1.00E+00 1.55 ABCB1 rs2235018 Intron 6 A G 0.67 0.81 9.65EÀ02 2.09EÀ01 1.40EÀ01 4.13 ABCB1 rs10256836a Intron 5 C G 0.13 0.09 5.68EÀ01 1.00E+00 5.31EÀ01 1.73 ABCB1 rs10259849a Intron 5 C T 0.14 0.10 5.75EÀ01 1.00E+00 5.36EÀ01 1.65 ABCB1 rs1202172 Intron 5 T G 0.96 0.86 1.01EÀ01 8.01EÀ02 1.00E+00 4.00 Table 2 Continued Allele Frequency of allele 1 Fisher test`s P-values Gene name SNP ID Position of SNP/functional SNP 1 2 dCase eControl f1vs2 g11vs h22vs Odds ratio ABCB1 rs17327442 Intron 5 T A 0.89 0.94 5.12EÀ01 4.93EÀ01 1.00E+00 1.87 ABCB1 rs1202184 Intron 5 G A 0.24 0.33 3.44EÀ01 1.00E+00 2.25EÀ01 1.91 ABCB1 rs3789243 Intron 4 T C 0.50 0.31 2.81EÀ02 5.05EÀ02 1.38EÀ01 3.50 ABCB1 rs3213619 Exon 2 (5' UTR) C T 0.02 0.10 1.81EÀ01 1.00E+00 1.63EÀ01 5.02 ABCB1 rs4148732 Intron 1 A G 0.87 0.96 7.89EÀ02 6.87EÀ02 1.00E+00 3.67 ABCB1 rs13233308 Intron 1 T C 0.43 0.44 1.00E+00 7.60EÀ01 7.95EÀ01 0.82 ABCB1 rs1978095 Intron 1 T C 0.67 0.73 5.59EÀ01 6.21EÀ01 6.89EÀ01 1.36 ABCB1 rs2157929 Intron 1 T C 0.93 0.79 3.32EÀ02 5.60EÀ02 5.51EÀ01 3.81 ABCB1 rs10278483 Intron 1 T C 0.96 0.86 1.01EÀ01 1.36EÀ01 5.88EÀ01 3.34 CYP3A5 rs776746 Intron 3 (CYP3A5*3) A G 0.22 0.32 2.50EÀ01 6.67EÀ01 3.26EÀ01 1.79 CYP3A4 rs28371759c Exon 10 (Pro 293 Leu) (CYP3A4*18) 1.00 1.00 1.00E+00 1.00E+00 1.00E+00 NA CYP3A4 rs12721627b Exon 7 (Ser 185 Thr) (CYP3A4*16) C G 1.00 0.96 3.23EÀ01 3.22EÀ01 1.00E+00 NA ABCC2 rs12268782 5' near gene A G 0.22 0.13 2.26EÀ01 1.00E+00 1.81EÀ01 2.21 ABCC2 rs2804398 Intron 7 T A 0.83 0.84 8.14EÀ01 7.90EÀ01 1.00E+00 1.29 ABCC2 rs2756109 Intron 7 G T 0.63 0.65 8.55EÀ01 1.00E+00 1.00E+00 1.12 ABCC2 rs2273697 Exon 10 (Ile 417 Val) G A 0.83 0.92 8.91EÀ02 5.96EÀ02 1.00E+00 3.33 ABCC2 rs11190291a Intron 11 T C 0.17 0.08 8.91EÀ02 1.00E+00 5.96EÀ02 3.33 ABCC2 rs2002042 Intron 19 T C 0.33 0.39 4.78EÀ01 2.78EÀ01 1.00E+00 3.52 ABCC2 rs17222723c Exon 25 (Glu 1188 Val) T A 1.00 1.00 1.00E+00 1.00E+00 1.00E+00 NA ABCC2 rs3740065b Intron 29 T C 0.65 0.60 5.96EÀ01 6.18EÀ01 9.90EÀ02 6.36 ABCC2 rs12762549 3' near gene C G 0.48 0.36 2.13EÀ01 1.00E+00 6.81EÀ02 3.35 ABCC2 rs2862691 3' near gene T C 0.19 0.25 5.26EÀ01 6.05EÀ01 6.11EÀ01 NA ABCC2 rs11598781 3' near gene T C 0.17 0.27 2.30EÀ01 1.00E+00 1.40EÀ01 2.29 ABCC2 rs11190303 3' near gene T C 0.24 0.33 2.62EÀ01 5.33EÀ02 1.00E+00 NA SLCO1B3 rs12228798 Intron 1 C T 0.82 0.83 1.00E+00 7.77EÀ01 2.27EÀ01 NA SLCO1B3 rs7977213 Intron 2 G C 0.43 0.18 1.29EÀ03 1.31EÀ03 2.55EÀ02 NA SLCO1B3 rs10841661 Intron 2 T C 0.48 0.23 2.73EÀ03 5.65EÀ03 4.79EÀ02 9.88 SLCO1B3 rs4149118 Intron 4 A G 0.59 0.48 3.31EÀ01 3.49EÀ01 5.40EÀ01 1.85 SLCO1B3 rs3764009a Intron 4 A G 0.68 0.69 1.00E+00 1.00E+00 1.00E+00 1.16 SLCO1B3 rs7311358 Exon 7 (Ile 233 Met) A G 0.68 0.69 1.00E+00 1.00E+00 1.00E+00 1.16 SLCO1B3 rs11045585b Intron 12 G A 0.13 0.21 2.76EÀ01 3.14EÀ01 6.06EÀ01 NA SLCO1B3 rs980084 Intron 12 G C 0.28 0.45 7.48EÀ02 3.80EÀ01 7.66EÀ02 2.67 SLCO1B3 rs3764006 Exon 14 (Gly 611 Gly) T C 0.87 0.70 2.74EÀ02 1.32EÀ01 9.75EÀ02 NA SLCO1B3 rs919840 3' near gene C G 0.97 0.90 2.99EÀ01 2.77EÀ01 1.00E+00 3.74 SLCO1B3 rs2117032 3' near gene T C 0.52 0.47 6.05EÀ01 7.68EÀ01 7.82EÀ01 1.35 SLCO1B3 rs7312051 3' near gene C T 1.00 0.91 1.26EÀ01 1.04EÀ01 1.00E+00 NA SLCO1B3 rs10841714 3' near gene C T 0.15 0.17 8.01EÀ01 1.00E+00 1.00E+00 NA SLCO1B3 rs2174012 3' near gene T C 0.62 0.63 1.00E+00 5.72EÀ01 4.55EÀ01 0.39 SLCO1B3 rs11045639a 3' near gene G A 0.65 0.72 4.46EÀ01 2.17EÀ01 7.25EÀ01 2.05 SLCO1B3 rs2900459 3' near gene G A 0.46 0.56 2.95EÀ01 1.43EÀ02 5.70EÀ01 5.96 SLCO1B3 rs4762693 3' near gene G A 0.65 0.72 4.46EÀ01 2.17EÀ01 7.25EÀ01 2.05 SLCO1B3 rs10734711 3' near gene A G 0.28 0.35 4.61EÀ01 2.78EÀ01 8.05EÀ01 3.52 SLCO1B1 rs12228427 5' near gene (LST-3TM12 Intron 9) A G 0.96 0.88 1.59EÀ01 1.36EÀ01 1.00E+00 3.34 SLCO1B1 rs1910163 5' near gene (LST-3TM12 Intron 12) A T 0.28 0.34 4.66EÀ01 7.25EÀ01 6.21EÀ01 1.44 SLCO1B1 rs6487207 5' near gene (LST-3TM12 Intron 11) T G 0.78 0.73 5.54EÀ01 8.11EÀ01 3.22EÀ01 NA SLCO1B1 rs1604539 5' near gene (LST-3TM12 Intron 12) T G 0.80 0.75 5.41EÀ01 6.18EÀ01 1.00E+00 1.42 SLCO1B1 rs7973691 5' near gene T C 0.80 0.83 8.21EÀ01 7.98EÀ01 1.00E+00 1.22 SLCO1B1 rs10743408 Intron 2 C G 0.24 0.18 4.97EÀ01 1.00E+00 3.06EÀ01 1.73 SLCO1B1 rs976754 Intron 2 T C 0.83 0.69 1.15EÀ01 8.67EÀ02 6.67EÀ01 2.54 SLCO1B1 rs2291073 Intron 3 T G 0.78 0.72 4.35EÀ01 8.11EÀ01 1.76EÀ01 NA SLCO1B1 rs4149037 Intron 4 A G 0.70 0.80 2.12EÀ01 2.07EÀ01 6.19EÀ01 2.07 SLCO1B1 rs4149056 Exon 5 (Ala 174 Val) T C 0.72 0.84 8.02EÀ02 2.04EÀ01 8.01EÀ02 NA SLCO1B1 rs2417967 Intron 11 A G 0.33 0.21 1.54EÀ01 1.00E+00 8.68EÀ02 2.41 SLCO1B1 rs7969341b Intron 14 T C 0.50 0.46 7.24EÀ01 1.58EÀ01 5.60EÀ02 3.80 SLCO1B1 rs4149085 3' UTR T C 0.74 0.66 4.53EÀ01 8.05EÀ01 1.76EÀ01 NA SLCO1B1 rs12372067 3' near gene C A 0.21 0.33 2.06EÀ01 1.00E+00 1.68EÀ01 2.42 SLCO1B1 rs12310063 3' near gene A C 0.67 0.76 3.21EÀ01 2.13EÀ01 1.00E+00 2.07 ABCC1 rs8050881 5' near gene A G 0.33 0.23 2.37EÀ01 1.00E+00 1.44EÀ01 2.13 ABCC1 rs4148330 5' near gene G A 0.48 0.34 1.46EÀ01 2.95EÀ01 2.13EÀ01 2.02 Continued Allele Frequency of allele 1 Fisher test`s P-values Gene name SNP ID Position of SNP/functional SNP 1 2 dCase eControl f1vs2 g11vs h22vs Odds ratio ABCC1 rs7190484 Intron 1 T C 0.43 0.34 3.67EÀ01 5.03EÀ01 4.62EÀ01 1.52 ABCC1 rs215098 Intron 1 C A 0.41 0.34 4.63EÀ01 1.96EÀ01 1.00E+00 2.30 ABCC1 rs215096 Intron 1 T C 0.89 0.87 1.00E+00 5.63EÀ01 2.89EÀ01 0.00 ABCC1 rs152023 Intron 1 G A 0.48 0.41 4.75EÀ01 3.79EÀ01 8.05EÀ01 1.79 ABCC1 rs6498595 Intron 1 G C 0.41 0.31 2.70EÀ01 2.73EÀ02 1.00E+00 4.76 ABCC1 rs7196970 Intron 1 C G 0.70 0.63 4.71EÀ01 3.25EÀ01 1.00E+00 1.73 ABCC1 rs12935283 Intron 1 A G 0.67 0.61 4.78EÀ01 3.19EÀ01 1.00E+00 1.79 ABCC1 rs246240 Intron 5 A G 0.60 0.58 1.00E+00 1.00E+00 1.00E+00 1.06 ABCC1 rs924138b Intron 5 T C 0.68 0.63 5.84EÀ01 6.17EÀ01 1.00E+00 1.38 ABCC1 rs2062541 Intron 6 C T 0.71 0.64 4.46EÀ01 4.45EÀ01 7.51EÀ01 1.60 ABCC1 rs11647513 Intron 6 C T 0.78 0.70 3.34EÀ01 2.14EÀ01 1.00E+00 2.13 ABCC1 rs35593 Intron 11 T C 0.71 0.75 8.37EÀ01 1.00E+00 1.00E+00 2.70 ABCC1 rs3765129 Intron 11 C T 0.98 0.84 2.69EÀ02 1.75EÀ02 1.00E+00 9.90 ABCC1 rs17287570 Intron 12 A C 0.73 0.91 6.32EÀ03 1.03EÀ02 2.75EÀ01 4.27 ABCC1 rs35597 Intron 12 A G 0.59 0.55 7.19EÀ01 5.85EÀ01 1.00E+00 1.45 ABCC1 rs35598a Intron 12 A G 0.82 0.86 6.21EÀ01 7.86EÀ01 2.78EÀ01 NA ABCC1 rs9932506 Intron 12 G A 0.72 0.75 6.94EÀ01 6.21EÀ01 1.00E+00 1.44 ABCC1 rs35604 Intron 12 G A 0.24 0.25 1.00E+00 1.00E+00 1.00E+00 1.63 ABCC1 rs35606 Intron 13 C T 0.82 0.86 6.17EÀ01 7.82EÀ01 2.86EÀ01 NA ABCC1 rs35620 Intron 14 G C 0.26 0.23 8.39EÀ01 1.00E+00 6.19EÀ01 1.39 ABCC1 rs35625 Intron 14 C T 0.41 0.34 4.70EÀ01 7.52EÀ01 4.72EÀ01 1.45 ABCC1 rs35626 Intron 15 T G 0.43 0.40 7.21EÀ01 5.08EÀ01 2.96EÀ01 1.93 ABCC1 rs4148353 Intron 15 T G 0.20 0.07 2.42EÀ02 1.00E+00 1.69EÀ02 4.02 ABCC1 rs35629 Intron 15 C T 0.80 0.76 5.46EÀ01 6.24EÀ01 1.00E+00 1.32 ABCC1 rs2269800 Intron 20 A G 0.74 0.66 4.53EÀ01 8.06EÀ01 2.78EÀ01 3.52 ABCC1 rs11864374 Intron 21 G A 0.78 0.77 8.41EÀ01 1.00E+00 1.00E+00 1.63 ABCC1 rs3887893 Intron 22 A G 0.48 0.46 8.62EÀ01 2.30EÀ01 5.85EÀ01 2.10 ABCC1 rs4148376 Intron 23 A G 0.93 0.95 1.00E+00 1.00E+00 1.00E+00 1.30 ABCC1 rs2238475 Intron 23 C A 0.11 0.18 3.45EÀ01 1.00E+00 4.21EÀ01 1.80 ABCC1 rs212079 Intron 26 G A 0.76 0.83 3.77EÀ01 1.00E+00 6.71EÀ02 8.55 ABCC1 rs2283512 Intron 26 G T 0.48 0.46 1.00E+00 7.68EÀ01 1.00E+00 1.32 ABCC1 rs212081 Intron 27 T C 0.20 0.22 8.34EÀ01 5.73EÀ01 4.61EÀ01 1.50 ABCC1 rs212084 Intron 28 G A 0.68 0.77 2.90EÀ01 3.02EÀ01 6.00EÀ01 1.81 ABCC1 rs212087 Intron 28 C T 0.57 0.70 1.41EÀ01 1.38EÀ01 3.45EÀ01 2.30 ABCC1 rs4148380 3' UTR G A 0.87 0.89 7.88EÀ01 7.75EÀ01 1.00E+00 1.22 ABCC1 rs212091 3' UTR G A 0.22 0.34 1.84EÀ01 2.68EÀ01 3.35EÀ01 4.04 ABCC1 rs12448760 3' near gene G A 0.82 0.89 2.95EÀ01 3.79EÀ01 1.00E+00 1.79 ABCC1 rs9932935 3' near gene (ABCC6 Intron 29) A T 0.96 0.91 5.12EÀ01 5.00EÀ01 1.00E+00 1.93 ABCC1 rs2066738 3' near gene (ABCC6 Intron 28) C T 0.74 0.90 1.50EÀ02 5.28EÀ02 7.81EÀ02 2.95 ABCC1 rs169845 3' near gene (ABCC6 Intron 27) G C 0.26 0.40 1.04EÀ01 3.28EÀ01 2.13EÀ01 2.07 ABCC1 rs2238471 3' near gene (ABCC6 Intron 26) A C 0.93 0.81 5.49EÀ02 5.79EÀ02 1.00E+00 3.78 ABCC1 rs3213471 3' near gene (ABCC6 Intron 24) A G 0.91 0.92 1.00E+00 7.33EÀ01 1.00E+00 1.32 ABCC1 rs3213473 3' near gene (ABCC6 Intron 24) T G 0.16 0.13 7.98EÀ01 1.00E+00 7.71EÀ01 1.27 CES2 rs3843712 5' near gene G A 0.18 0.12 4.41EÀ01 1.00E+00 4.00EÀ01 1.80 CES2 rs8062110 5' near gene G C 0.61 0.65 7.16EÀ01 1.00E+00 7.28EÀ01 1.39 CES2 rs4783744 5' near gene G A 0.66 0.62 8.37EÀ01 7.76EÀ01 1.00E+00 1.24 CES2 rs7194513 5' near gene G A 0.26 0.27 1.00E+00 3.14EÀ01 6.29EÀ01 NA CES2 rs28382812c Exon 1 (Ile 37 Ile) C T 1.00 1.00 1.00E+00 1.00E+00 1.00E+00 NA CES2 rs2241410 Intron 2 T G 0.10 0.11 7.85EÀ01 1.00E+00 7.71EÀ01 1.26 CES2 rs2303218 Intron 2 G A 0.09 0.21 1.03EÀ01 5.55EÀ01 1.15EÀ01 2.70 CES2 rs8192924c Exon 5 (His 270 Arg) G A 1.00 1.00 1.00E+00 1.00E+00 1.00E+00 NA CES2 rs28382827c Exon 12 (Leu 613 Leu) C T 1.00 1.00 1.00E+00 1.00E+00 1.00E+00 NA Abbreviations: Chrom, chromosome; HWE, Hardy-Weinberg equilibrium; NA, not available; SNP, single nucleotide polymorphism. 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PMID: 19696793 [PubMed] Low SK et al: "Association study of genetic polymorphism in ABCC4 with cyclophosphamide-induced adverse drug reactions in breast cancer patients."

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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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