ABCMdb

PMID: 19568750

Sun N, Sun X, Chen B, Cheng H, Feng J, Cheng L, Lu Z
MRP2 and GSTP1 polymorphisms and chemotherapy response in advanced non-small cell lung cancer.
Cancer Chemother Pharmacol. 2010 Feb;65(3):437-46. Epub 2009 Jul 1., [PubMed]

Sentences

No. Mutations Sentence Comment

4 ABCC2 p.Val417Ile MRP2 C-24T (¡24C>T), MRP2 Val417Ile (1249G>A), MRP2 Ile1324Ile (3972C>T), and GSTP1 Ile105Val (342A>G) genotype were determined by gene-chip method (a 3-D (three dimensions) polyacrylamide gel-based DNA microarray method) using DNA samples isolated from peripheral blood collected before treatment. Login to comment 96 ABCC2 p.Val417Ile Table 2 Sequences of primers and probes Locus Primers and probes MRP2 Forward primer: 5Ј-CCTTTACGGAGAACATCAGA-3Ј (C-24T, rs717620) Reverse primer: 5Ј-Acrydite™-TTTGCATTACATTTCCCAGA-3Ј Probe: 5Ј-Cy3-AGTCTTCGTTCCA-3Ј 5Ј-Cy5-AGTCTTTGTTCCA-3Ј MRP2 (Val 417 Ile) Forward primer: 5Ј-TGGAGGCAAGAAGTCACAGT-3Ј (G1249A, rs2273697) Reverse primer: 5Ј-Acrydite™-GATTACAAGCACCATCACCC-3Ј Probe: 5Ј-Cy3-TACACCGTTGGAG-3Ј 5Ј-Cy5-TACACCATTGGAG-3Ј MRP2 (Ile 1,324 Ile) Forward primer: 5Ј-Acrydite™-CACTGCTACCCTTCTCCTGTTC-3Ј (C3972T, rs3740066) Reverse primer: 5Ј-CTGACCCTTTCCCTCCATCC-3Ј Probe: 5Ј-Cy3-GCTACCGATGTCA-3Ј 5Ј-Cy5-GCTACCAATGTCA-3Ј GSTP1 (Ile 105 Val) Forward primer: 5Ј-CAGGGCTCTATGGGAAGGAC-3Ј (A342G, rs1695) Reverse primer: 5Ј-Acrydite™-CAGGAGATCAGAAACCACCAGTT-3Ј Probe: 5Ј-Cy3-AAATACATCTCCC-3Ј 5Ј-Cy5-AAATACGTCTCCC-3Ј Fig. 1 Microarray hybridization scanning patterns of SNPs genotyping. Login to comment 97 ABCC2 p.Val417Ile A, B, C and D the microarray images of locus MRP2 C-24T, MRP2 Val417Ile, MRP2 Ile1324Ile and GSTP1 Ile105Val; green, yellow and red represent wild, hybrid and mutation type, respectively. Login to comment 116 ABCC2 p.Val417Ile A signiWcant P value indicates that there is an association between the Table 3 Genotype and response to chemotherapy among NSCLC patients (n = 113) Adjusted OR (95% CI): OR (95% CI) after adjusting for patient gender, age at diagnosis, tumor histology, disease stage, and chemotherapy regimens Genotype Cases Response to chemotherapy OR (95% CI) P value Adjusted OR (95% CI) Adjusted P value CR + PR (%) n = 30 SD + PD (%) n = 83 MRP2 (C-24T) C/C 66 11 (36.7) 55 (66.3) 1 0.015 4.069 (1.518-10.910) 0.005 C/T 43 16 (53.3) 27 (32.5) 2.959 (1.211-7.246) 0.023 10.514 (0.842-131.319) 0.068 T/T 4 3 (10.0) 1 (1.2) 14.925 (1.425-166.667) 0.005 4.493 (1.728-11.682) 0.002 C/T+T/T 47 19 (63.3) 28 (33.7) 3.390 (1.420-8.130) MRP2 (Val417Ile) G/G 84 20 (66.7) 64 (77.1) 1 G/A 26 9 (30.0) 17 (20.5) 1.695 (0.654-4.386) 0.274 1.910 (0.697-5.229) 0.208 A/A 3 1 (3.3) 2 (2.4) 1.600 (0.138-18.519) 0.568 1.616 (0.115-22.779) 0.722 G/A+A/A 29 10 (33.3) 19 (22.9) 1.684 (0.674-4.202) 0.262 1.879 (0.710-4.968) 0.204 MRP2 (Ile1324Ile) C/C 74 20 (66.7) 54 (65.1) 1 C/T 33 8 (26.7) 25 (30.1) 0.864 (0.335-2.227) 0.762 1.066 (0.385-2.951) 0.901 T/T 6 2 (6.7) 4 (4.8) 1.350 (0.229-7.937) 0.665 1.508 (0.210-10.830) 0.683 C/T+T/T 39 10 (33.3) 29 (34.9) 0.931 (0.385-2.252) 0.874 1.133 (0.441-2.911) 0.796 GSTP1 (Ile105Val) A/A 71 13 (43.3) 58 (69.9) 1 A/G 38 15 (50.0) 23 (27.7) 2.907 (1.200-7.042) 0.016 2.788 (1.106-7.029) 0.030 G/G 4 2 (6.7) 2 (2.4) 4.464 (0.574-34.483) 0.176 4.083 (0.457-36.463) 0.208 A/G+G/G 42 17 (56.7) 25 (30.1) 3.030 (1.282-7.194) 0.010 2.881 (1.167-7.113) 0.022 haplotype C-A (MRP2-24C and GSTP1105A) and the treatment response. Login to comment 137 ABCC2 p.Val417Ile ABCC2 p.Val417Ile Table 4 Allele frequencies Locus Allele Frequency Standard Error 95% CI MRP2 (C-24T) C 0.7743 0.0265 0.7168-0.8230 T 0.2257 0.0265 0.1770-0.2832 MRP2 (Val417Ile) A 0.1416 0.0238 0.0973-0.1903 G 0.8584 0.0238 0.8097-0.9027 MRP2 (Ile1324Ile) C 0.8009 0.0277 0.7434-0.8540 T 0.1991 0.0277 0.1460-0.2566 GSTP1 (Ile105Val) A 0.7965 0.0263 0.7434-0.8451 G 0.2035 0.0263 0.1549-0.2566 Table 5 Genotype frequencies Locus Genotype Frequency HWD coeV Standard error 95% CI MRP2 (C-24T) C/C 0.5841 ¡0.0155 0.0151 ¡0.0459-0.0149 C/T 0.3805 ¡0.0155 0.0151 ¡0.0459-0.0149 T/T 0.0354 ¡0.0155 0.0151 ¡0.0459-0.0149 MRP2 (Val417Ile) A/A 0.0265 0.0065 0.0126 ¡0.0165-0.0318 A/G 0.2301 0.0065 0.0126 ¡0.0165-0.0318 G/G 0.7434 0.0065 0.0126 ¡0.0165-0.0318 MRP2 (Ile1324Ile) C/C 0.6549 0.0135 0.0163 ¡0.0185-0.0484 C/T 0.2920 0.0135 0.0163 ¡0.0185-0.0484 T/T 0.0531 0.0135 0.0163 ¡0.0185-0.0484 GSTP1 (Ile105Val) A/A 0.6283 ¡0.0060 0.0146 ¡0.0313-0.0218 A/G 0.3363 ¡0.0060 0.0146 ¡0.0313-0.0218 G/G 0.0354 ¡0.0060 0.0146 ¡0.0313-0.0218 Board et al. Login to comment 161 ABCC2 p.Val417Ile G1249A polymorphism is a G!A base change that results in amino acid alterations from Val to Ile at 417, and 1,249 AA is associated with decreased mRNA [44]; whereas C3972T is the 'silent` mutation at 1,324 (Ile1324Ile). Login to comment