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CDA and MTHFR polymorphisms are associated with clinical outcomes in gastroenteric cancer patients treated with capecitabine-based chemotherapy

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Abstract

Purpose

The impact of pharmacogenetics on predicting survival in gastroenteric cancer remains unclear.

Methods

We tested 322 consecutive patients treated with capecitabine-based chemotherapy for CDA and MTHFR polymorphisms.

Results

Patients who carried the CDA 79 A>C (rs2072671) CC genotype showed significantly shorter progression-free survival (PFS) comparing with A-allele (P = 0.008). A significant better PFS was found in the patients with 451 A>G (rs532545) G-allele (P = 0.002) and 92 C>T (rs602950) T-allele (P = 0.002). In addition, a shorter PFS was also observed in patients with MTHFR 1298 A>C (rs1801131) CC genotype than the patients with AC or AA genotype after capecitabine-based chemotherapy (P = 0.002). Furthermore, the colon, female, or elder (> 65 years old) patients with MTHFR 1298 A>C CC genotype had poorer PFS than A-allele. Moreover, CDA 451 A>G was independent predictors of chemotherapy-induced toxicity in colon patients. Multivariate Cox regression analysis demonstrated that the CDA 79 A>C CC, 451 A>G AA, 92 C>T CC, and MTHFR 1298 A>C CC were predictive of shorter PFS in gastroenteric cancer patients.

Conclusions

The results reminded us those gastroenteric cancer patients with CDA 79 A>C CC, 451 A>G AA, 92 C>T CC, or MTHFR 1298 A>C CC genotype are not likely to benefit from the therapy of capecitabine-based chemotherapy.

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Acknowledgements

This study was supported by the Program for Haiyan fund of Harbin Medical University Cancer Hospital (General Program) (Grant no. JJMS2014-01); “The mechanism of capecitabine-induced hand-foot syndrome” (Grant no. YJHYXKYJJ-703). The Fundamental Research Funds for the Provincial Universities (Grant no. 2017LCZX75); China Postdoctoral Science Foundation (Grant no. 2018M631952); Heilongjiang Postdoctoral Fund (Grant no. LBH-Z17148); Youth science of Harbin Medical University Cancer Hospital (Grant no. BJQN2018-03), and Chinese Medical Association Clinical Pharmacy Branch-Wu Jieping Medical Foundation Research Fund (Grant No. LCYX-Q031).

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Authors and Affiliations

  1. Department of Pharmacy, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China

    Duo Liu, Xiang Li, Xuehua Li, Juan Zhang, Dan Hou, Zhiqiang Tong & Mei Dong

  2. Laboratory Department, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China

    Mingyan Zhang

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  1. Duo Liu
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Correspondence to Mei Dong.

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Liu, D., Li, X., Li, X. et al. CDA and MTHFR polymorphisms are associated with clinical outcomes in gastroenteric cancer patients treated with capecitabine-based chemotherapy. Cancer Chemother Pharmacol 83, 939–949 (2019). https://doi.org/10.1007/s00280-019-03809-2

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