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



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


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


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.


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.


Gastroenteric cancer Capecitabine CDA MTHFR Polymorphism Prognosis 



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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