CDA and MTHFR polymorphisms are associated with clinical outcomes in gastroenteric cancer patients treated with capecitabine-based chemotherapy
| Autor: | Mei Dong, Xiang Li, Duo Liu, Mingyan Zhang, Juan Zhang, Zhi-Qiang Tong, Dan Hou, Xuehua Li |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male 0301 basic medicine Antimetabolites Antineoplastic Cancer Research medicine.medical_specialty Genotype medicine.medical_treatment Toxicology Polymorphism Single Nucleotide Gastroenterology Capecitabine 03 medical and health sciences 0302 clinical medicine Cytidine Deaminase Internal medicine medicine Humans Pharmacology (medical) In patient Alleles Methylenetetrahydrofolate Reductase (NADPH2) Aged Gastrointestinal Neoplasms Pharmacology Chemotherapy biology Proportional hazards model business.industry Middle Aged Progression-Free Survival digestive system diseases 030104 developmental biology Oncology Pharmacogenetics 030220 oncology & carcinogenesis Methylenetetrahydrofolate reductase Toxicity biology.protein Female business medicine.drug |
| Zdroj: | Cancer Chemotherapy and Pharmacology. 83:939-949 |
| ISSN: | 1432-0843 0344-5704 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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