title: GSTP1 and MTHFR polymorphisms are related with toxicity in breast cancer adjuvant anthracycline-based treatment.
abstract: We have analyzed several members of drug-metabolizing enzymes (DMEs) and other polymorphisms in genes implicated in tumor aggressivity regarding possible links between specific genetic variability in systemic drug bioavailability and toxicity in breast cancer patients treated with adjuvant anthracycline-based treatment. PCR-RFLP and sequencing analyses technique were used for evaluating fourteen previously identified polymorphisms in 94 patients. GSTP1A>G and MTHFR 1298A>C genotypes remained as significant predictors in a multivariate logistic regression analysis. GSTP1 polymorphism was linked to haematological GIII-IV toxicity (P = 0.044, HR= 6.4, 95% CI = 1.05 to 39. Increased and significant HR was obtained for MTHFR-1298 AC+CC group when non-haematological toxicities GIII-IV toxicities were evaluated (HR = 24; 95% CI = 2.3 to 254), P = 0.008. Our results suggest that GSTP1 and MTHFR genotypes may be consider relevant and independent factors of toxicity in adjuvant anthracycline-based treatment of breast cancer.
authors.affiliation: Laboratory of Biotechnology, University Clinic of Navarra, Pamplona, Spain. rzarate@unav.es
authors.forename: R
authors.initials: R
authors.lastname: Zárate
authors.forename: S
authors.initials: S
authors.lastname: González-Santigo
authors.forename: J
authors.initials: J
authors.lastname: de la Haba
authors.forename: E
authors.initials: E
authors.lastname: Bandres
authors.forename: R
authors.initials: R
authors.lastname: Morales
authors.forename: J
authors.initials: J
authors.lastname: Salgado
authors.forename: A
authors.initials: A
authors.lastname: Gómez
authors.forename: E
authors.initials: E
authors.lastname: Aranda
authors.forename: J
authors.initials: J
authors.lastname: García-Foncillas
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000009:adverse effects* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy*; D005260:Female; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D012189:Retrospective Studies
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents; D042965:Methylenetetrahydrofolate Reductase (NADPH2); C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi