ABCMdb

PMID: 21887680

Windsor RE, Strauss SJ, Kallis C, Wood NE, Whelan JS
Germline genetic polymorphisms may influence chemotherapy response and disease outcome in osteosarcoma: a pilot study.
Cancer. 2012 Apr 1;118(7):1856-67. doi: 10.1002/cncr.26472. Epub 2011 Sep 1., [PubMed]

Sentences

No. Mutations Sentence Comment

44 ABCG2 p.Gln141Lys ABCC2 p.Val417Ile ABCC2 p.Val1188Glu 3R adverse prognosis in ALL.45 ABC efflux ABCB1 (MDR1) 7q21.12 MAP 1128503 1236C>T Gly412 Gly T allele : exposure to doxorubicin in breast cancer patients.4 No association in platinum-treated ovarian cancer.5 1045642 3435C>T Ile145 Ile CC : response to platinum chemotherapy in NSCLC.6 No association in platinum-treated ovarian cancer.5 ABCG2 (BCRP) 4q22.1 MAP 2231142 421C>A Gln141 Lys A ; OS in platinum-treated lung cancer.7 No association in platinum-treated ovarian cancer.5 ABCC1 (MRP1) 6p13.11 M 246240 A>G G ; methotrexate toxicity in psoriasis.8 3784862 A>G ABCC2 10q24.2 M 717620 24C>T T : response to platinum chemotherapy in NSCLC.9 No association in ovarian cancer.5 2273697 1249G>A Val417 Ile No association with response to platinum chemotherapy in NSCLC.9 17222723 3563T>A Val1188 Glu A : acute ACT, in 100% LD with Cis1515 Tyr.10 8087710 4544G>A Cis1515 Tyr DNA repair ERCC1 19q13.32 A, P 3212986 1510C>A (8092C>A)* Clinical effects conflicting. Login to comment 140 ABCC2 p.Val1188Glu Significant Genotypic Associations With Grade 3-4 Chemotherapy Toxicity Cycle Pathway Toxicity Polymorphism Genotype OR (95% CI) P Methotrexate Folate pathway Anemia MTHFD1 c.1958G>A p.Arg653 Gln GG Reference AG 3.6 (0.6-20.9) .15 AA 10.2 (1.5-67.2) .016 AG/AA 5.4 (1-27.5) .044 MTHFR c.1298A>C p.Glu429 Ala AA Reference AC 3.8 (0.8-16.9) .08 CC 10 (1.1-86.9) .037 AC/AA 4.6 (1.1-19.2) .038 Recurrent [any] MTHFR c.1298A>C p.Glu429 Ala AA Reference AC 4.9 (1.3-19.1) .022 CC 4.4 (0.4-45.3) .2 AC/AA 4.8 (1.3-17.1) .015 ABC efflux Leucopenia ABCC2 3563T>A Val1188 Glu [wild-type AA] AA Reference AT 4 (0.96-17.1) .057 TT 9.9 (0.4-265) .17 AT/TT 5.2 (1.2-22.4) .028 Mucositis ABCB1 c.3435T>C p.Ile145 Ile TT Reference CT 5.2 (0.9-30.6) .06 CC 7.5 (1.3-44) .026 CT/CC 6.2 (1.2-31.8) .027 Recurrent [any] ABCG2 c.421C>A p.Gln141 Lys CC Reference AC 0.1 (0.01-1) .05 AA Nil Doxorubicin/cisplatin A metabolism Anemia CYBA c.242C>T p.His72 Tyr CC Reference CT 0.2 (0.06-0.9) .029 TT 0.5 (0.9-2.7) .4 CT/TT 0.3 (0.09-0.9) .038 Mucositis CYBA c.242C>T p.His72 Tyr CC Reference CT 0.2 (0.5-0.75) .018 TT 0.5 (0.1-2.9) .47 CT/TT 0.3 (0.08-0.9) .028 DNA repair Mucositis ERCC1 c.354T>C p.Asn118 Asn [wild-type CC] CC Reference CT 1.1 (0.3-3.9) .9 TT 0.1 (0.01-0.9) .045 CT/TT 0.6 (0.2-1.9) .4 Doxorubicin DNA repair Infection XPC 2886A>C Lys939 Gln AA Reference AC 0.2 (0.04-0.8) .03 CC 0.3 (0.04-2) .2 AC/CC 0.2 (0.06-0.8) .024 ERCC1 c.1510C>A p.Gln504 Lys CC Reference AC 3.7 (0.9-15.2) .06 AA 3.7 (0.5-28.4) .2 AC/AA 3.7 (1-13.7) .047 Leucopenia ERCC1 c.1510C>A p.Gln504 Lys CC Reference AC 5.4 (1-29.6) .05 AA 5.4 (0.4-66.7) .19 AC/AA 5.4 (1.1-26) .036 GST enzymes Treatment delay GSTM1 Non-null Reference Null 9.4 (1.9-46.9) .006 Leucopenia GSTP1 c.313A>G p.Ile105 Val AA Reference AG 6.8 (1.5-31.2) .013 GG 4 (0.2-91) .39 AG/GG 7.8 (1.3-47) .024 Abbreviations: CI, confidence interval; GST, glutathione-S-transferase; OR, odds ratio. Login to comment