Duo Liu1, Xiang Li1, Xuehua Li1, Mingyan Zhang2, Juan Zhang1, Dan Hou1, Zhiqiang Tong1, Mei Dong3. 1. Department of Pharmacy, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China. 2. Laboratory Department, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China. 3. Department of Pharmacy, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China. 13804567370@163.com.
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.
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 colonpatients. 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 cancerpatients. CONCLUSIONS: The results reminded us those gastroenteric cancerpatients 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.
Authors: Mohammad Hadi Abbasian; Nafiseh Ansarinejad; Bahareh Abbasi; Masoud Iravani; Tayeb Ramim; Fahime Hamedi; Ali M Ardekani Journal: Avicenna J Med Biotechnol Date: 2020 Jul-Sep