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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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PurposeThe impact of pharmacogenetics on predicting survival in gastroenteric cancer remains unclear.MethodsWe tested 322 consecutive patients treated with capecitabine-based chemotherapy for CDA and MTHFR polymorphisms.ResultsPatients who carried the CDA 79… Click to show full abstract

PurposeThe impact of pharmacogenetics on predicting survival in gastroenteric cancer remains unclear.MethodsWe tested 322 consecutive patients treated with capecitabine-based chemotherapy for CDA and MTHFR polymorphisms.ResultsPatients 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.ConclusionsThe 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: chemotherapy; capecitabine based; gastroenteric cancer; based chemotherapy; cancer

Journal Title: Cancer Chemotherapy and Pharmacology
Year Published: 2019

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