GSTP1 and MTHFR Polymorphisms Are Related with Toxicity in Breast Cancer Adjuvant Anthracycline-Based Treatment

Author(s): R. Zarate, S. Gonzalez-Santiago, E. Bandres, R. Morales, J. Salgado, A. Gomez, E. Aranda, J. Garcia-Foncillas

Journal Name: Current Drug Metabolism

Volume 8 , Issue 5 , 2007

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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.

Keywords: Anthracycline, breast cancer, drug-metabolizing enzymes, GSTP1, MTHFR, polymorphisms

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Article Details

Year: 2007
Page: [481 - 486]
Pages: 6
DOI: 10.2174/138920007780866780
Price: $65

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