ABCMdb

PMID: 22112610

Tian C, Ambrosone CB, Darcy KM, Krivak TC, Armstrong DK, Bookman MA, Davis W, Zhao H, Moysich K, Gallion H, DeLoia JA
Common variants in ABCB1, ABCC2 and ABCG2 genes and clinical outcomes among women with advanced stage ovarian cancer treated with platinum and taxane-based chemotherapy: a Gynecologic Oncology Group study.
Gynecol Oncol. 2012 Mar;124(3):575-81. Epub 2011 Nov 21., [PubMed]

Sentences

No. Mutations Sentence Comment

4 ABCG2 p.Gln141Lys ABCG2 p.Gln141Lys ABCB1 p.Gly1249Ala ABCC2 p.Val417Ile Sequenom iPLEXTMGOLD Assay and MALDI-TOF platform were used to genotype the non-synonymous G2677T/A (rs2032582; encoding Ala893Ser/Thr) and synonymous C3435T (rs1045642; encoding Ile1145Ile) variants in ABCB1, the non-synonymous G1249A variant in ABCC2 (rs2273697; encoding Val417Ile), and the non-synonymous C421A variant in ABCG2 (rs2231142; encoding Q141K, Gln141Lys) in normal DNA from up to 511 women in Gynecologic Oncology Group (GOG) phase III trials, GOG-172 or GOG-182. Login to comment 57 ABCB1 p.Gly1249Ala Sequenom iPLEXTMGOLD Assay and MALDI-TOF platform were used to genotype the G2677T/ A (rs2032582) and C3435T (rs1045642) polymorphisms in ABCB1, the G1249A polymorphism in ABCC2 (rs2273697), and the C421A polymorphism in ABCG2 (rs2231142) in normal DNA as described previously [28]. Login to comment 84 ABCB1 p.Gly1249Ala (%) PFS OS HR 95% CI P value HR 95% CI P value ABCB1 (G2677T/A) GG 165 (32.7) Referent Referent GT+GA 259 (51.4) 0.98 0.79-1.22 0.856 0.88 0.69-1.11 0.271 TT+TA 80 (15.9) 1.02 0.76-1.38 0.877 0.93 0.67-1.29 0.663 GT+G A+TT+TA 339 (67.3) 0.99 0.81-1.22 0.924 0.89 0.71-1.11 0.299 ABCB1 (C3435T) CC 127 (25.8) Referent Referent CT 266 (54.1) 1.11 0.88-1.40 0.399 1.00 0.77-1.30 0.981 TT 99 (20.1) 0.98 0.73-1.32 0.908 0.88 0.64-1.23 0.454 CT+TT 365 (74.2) 1.07 0.86-1.34 0.550 0.97 0.76-1.24 0.803 ABCC2 (G1249A) GG 313 (61.7) Referent Referent GA 167 (32.9) 0.98 0.80-1.20 0.839 0.89 0.71-1.12 0.318 AA 27 (5.3) 1.62 1.06-2.48 0.025 0.86 0.52-1.44 0.572 GA+AA 194 (38.2) 1.04 0.86-1.27 0.692 0.89 0.71-1.11 0.281 ABCG2 (C421A) CC 404 (79.8) Referent Referent CA+AA 102 (20.2) 0.75 0.59-0.96 0.022 0.88 0.67-1.15 0.356 Hazard ratio (HR) with 95% confidence interval (CI) estimated from Cox model adjusted for cell type, stage/residual disease status, and treatment regimen. Login to comment 89 ABCB1 p.Gly1249Ala ABCC2 Polymorphism The G1249A polymorphism in ABCC2 was not associated with patient characteristics including race (data not shown). Login to comment 92 ABCB1 p.Gly1249Ala The G1249A variant in ABCC2 was not associated with OS (Table 2). Login to comment 103 ABCB1 p.Gly1249Ala Kaplan-Meier estimates of progression-free survival (PFS) by the G2677T/A polymorphorism in ABCB1 (a), the C3435T polymorphorism in ABCB1 (b), or the G1249A polymorphorism in ABCC2 (c). Login to comment 109 ABCG2 p.Gln141Lys The non-synonymous C421A polymorphism in ABCG2 results in an amino acid change, Gln141Lys. Login to comment 124 ABCC1 p.Ala893Ser Of the more than 50 SNPs identified in the ABCB1 gene, G2677T/A is a non-synonymous polymorphism (encoding Ala893Ser/Thr), and C3435T is a synonymous polymorphism (encoding Ile1145Ile) associated with reduced ABCB1 mRNA expression [44]. Login to comment 143 ABCB1 p.Gly1249Ala ABCC2 p.Val417Ile The G1249A polymorphism encodes Val417Ile, and one study reported that this polymorphism was associated with a higher activity of the intestinal transporter [50]. Login to comment 144 ABCB1 p.Gly1249Ala Our study did not demonstrate that the GA+AA genotypes vs GG genotype in the ABGCC2 G1249A polymorphism was associated with worse PFS or OS. Login to comment 146 ABCB1 p.Gly1249Ala The G1249A polymorphism was also studied in the ovarian cancer SCOTROC1 trial and found no association with PFS [47]. Login to comment 148 ABCB1 p.Gly1249Ala In summary, the present study analyzed common polymorphisms in ABCB1 (G2677T/A; C3435T), ABCC2 (G1249A) and ABCG2 (C421A) in relation to PFS and OS. Login to comment