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DPYD*2A and MTHFR C677T predict toxicity and efficacy, respectively, in patients on chemotherapy with 5-fluorouracil for colorectal cancer

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Abstract

Background

Significant inter-individual variation in the sensitivity to 5-fluorouracil (5-FU) represents a major therapeutic hindrance either by impairing drug response or inducing adverse drug reactions (ADRs). This study aimed at exploring the cause behind this inter-individual alterations in consequences of 5-fluorouracil-based chemotherapy by investigating the effects of DPYD*2A and MTHFR C677T polymorphisms on toxicity and response of 5-FU in Bangladeshi colorectal cancer patients.

Methods

Colorectal cancer patients (n = 161) receiving 5-FU-based chemotherapy were prospectively enrolled. DPYD and MTHFR polymorphisms were assessed in peripheral leukocytes. Multivariate analyses were applied to evaluate which variables could predict chemotherapy-induced toxicity and efficacy.

Results

Multivariate analyses showed that DPYD*2A polymorphism was a predictive factor (P = 0.023) for grade 3 and grade 4 5-fluorouracil-related toxicities. Although MTHFR C677T polymorphism might act as forecasters for grade 3 or grade 4 neutropenia, diarrhea, and mucositis, this polymorphism was found to increase significantly (P = 0.006) the response of 5-FU.

Conclusion

DPYD*2A and MTHFR C677T polymorphisms could explain 5-FU toxicity or clinical outcome in Bangladeshi colorectal patients.

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Acknowledgements

We are very grateful to all the patients, controls, physicians, and nurses. We are also grateful to the Department of Clinical Pharmacy and Pharmacology for the partial support to conduct this research project. The authors have no other relevant affiliations or financial involvement with any organization.

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Authors and Affiliations

  1. Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka, Dhaka, 1000, Bangladesh

    Noor Ahmed Nahid, Mohd Nazmul Hasan Apu, Md. Reazul Islam, Samia Shabnaz, Surid Mohammad Chowdhury, Maizbha Uddin Ahmed, Md. Siddiqul Islam & Abul Hasnat

  2. Department of Pharmacy, University of Asia Pacific, Dhaka, Bangladesh

    Zabun Nahar

  3. Department of Pharmacy, Noakhali Science and Technology University, Sonapur, Noakhali, 3814, Bangladesh

    Mohammad Safiqul Islam

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  1. Noor Ahmed Nahid
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Correspondence to Mohammad Safiqul Islam.

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All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Nahid, N.A., Apu, M.N.H., Islam, M.R. et al. DPYD*2A and MTHFR C677T predict toxicity and efficacy, respectively, in patients on chemotherapy with 5-fluorouracil for colorectal cancer. Cancer Chemother Pharmacol 81, 119–129 (2018). https://doi.org/10.1007/s00280-017-3478-3

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