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

  • Duo Liu
  • Xiang Li
  • Xuehua Li
  • Mingyan Zhang
  • Juan Zhang
  • Dan Hou
  • Zhiqiang Tong
  • Mei DongEmail author
Original Article

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.

Keywords

Gastroenteric cancer Capecitabine CDA MTHFR Polymorphism Prognosis 

Notes

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).

Compliance with ethical standards

Conflict of interest

The authors declare no competing financial interests.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Duo Liu
    • 1
  • Xiang Li
    • 1
  • Xuehua Li
    • 1
  • Mingyan Zhang
    • 2
  • Juan Zhang
    • 1
  • Dan Hou
    • 1
  • Zhiqiang Tong
    • 1
  • Mei Dong
    • 1
    Email author
  1. 1.Department of PharmacyHarbin Medical University Cancer HospitalHarbinChina
  2. 2.Laboratory DepartmentHarbin Medical University Cancer HospitalHarbinChina

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