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Relationship of MTHFR and NQO1 Pharmacogenetics and Chemotherapy Clinical Outcomes in Breast Cancer Patients

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Abstract

The study aimed at evaluating the influence of MTHFR 677C>T and NQO1 609C>T polymorphisms in toxicity and response to chemotherapy in breast cancer patients. These two genes are involved in the folate homeostasis and bioactivation of chemotherapeutic drugs, respectively. In this study, 243 patients treated with FEC/FAC/methotrexate chemotherapy regimen were recruited and followed up for toxicity (NCI-CTCAE ver. 3). While out of 243 patients, 115 patients who received neo-adjuvant chemotherapy (NACT) were followed for treatment response. Genetic analysis of MTHFR 677C>T and NQO1 609C>T was done by PCR–restriction fragment length polymorphism. We found significant association of variant genotype (TT) of NQO1 609C>T with grade 2–4 toxicity [OR 0.33 (0.13–0.88), P = 0.027] and with grade 2–4 anemia [OR 0.34 (0.12–0.95), P = 0.041]. However, no association of MTHFR 677C>T was seen with either response to NACT or drug-induced toxicity. The study provides useful information for prediction of clinical outcomes in breast cancer patients in terms of NQO1 609C>T by evaluating its association with chemotherapy-induced toxicity.

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The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, 226 014, India

    Pankaj Chaturvedi, Sonam Tulsyan & Balraj Mittal

  2. Department of Endocrine & Breast Surgery, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India

    Gaurav Agarwal

  3. Department of Radiotherapy, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India

    Punita Lal & Sushma Agrawal

  4. Department of Urology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India

    Rama D. Mittal

Authors
  1. Pankaj Chaturvedi
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  2. Sonam Tulsyan
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  3. Gaurav Agarwal
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  4. Punita Lal
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  5. Sushma Agrawal
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  6. Rama D. Mittal
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  7. Balraj Mittal
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Correspondence to Balraj Mittal.

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Chaturvedi, P., Tulsyan, S., Agarwal, G. et al. Relationship of MTHFR and NQO1 Pharmacogenetics and Chemotherapy Clinical Outcomes in Breast Cancer Patients. Biochem Genet 53, 211–222 (2015). https://doi.org/10.1007/s10528-015-9683-z

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  • DOI: https://doi.org/10.1007/s10528-015-9683-z

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