ABCMdb

PMID: 20638924

Henriquez-Hernandez LA, Murias-Rosales A, Gonzalez-Hernandez A, de Leon AC, Diaz-Chico N, Fernandez-Perez L
Distribution of TYMS, MTHFR, p53 and MDR1 gene polymorphisms in patients with breast cancer treated with neoadjuvant chemotherapy.
Cancer Epidemiol. 2010 Oct;34(5):634-8. Epub 2010 Jul 17., [PubMed]

Sentences

No. Mutations Sentence Comment

13 ABCC8 p.Cys677Thr Two linked no synonymous SNPs, C677T and A1298C, have been shown to alter enzyme activity and possibly 5-FU sensitivity [9,10]. Login to comment 14 ABCC8 p.Cys677Thr MTHFR C677T has been implicated in different adverse reactions [11]. Login to comment 17 ABCC8 p.Cys677Thr Mutations in the p53 gene are the most common genetic alterations in human Cancer Epidemiology 34 (2010) 634-638 A R T I C L E I N F O Article history: Accepted 20 June 2010 Available online 17 July 2010 Keywords: Breast cancer Neoadjuvant chemotherapy Toxicity Adverse reaction Polymorphism MTHFR p53 A B S T R A C T Purpose To investigate the role of TSER (TYMS), C677T (MTHFR), Arg72Pro (p53) and C3435T (MDR1) gene polymorphisms in breast cancer patients treated with 5-fluorouracil and cyclophosphamide-based neoadjuvant chemotherapy. Login to comment 18 ABCC8 p.Cys677Thr Results Observed allelic frequencies were: TSER, (2) 0.54 and (3) 0.46; MTHFR C677T, (C) 0.59 and (T) 0.41; p53 Arg72Pro, (Arg) 0.73 and (Pro) 0.27; MDR1 C3435T, (C) 0.52 and (T) 0.48. Login to comment 35 ABCC8 p.Cys677Thr Because these gene polymorphisms have been proposed as important factors in chemotherapy response, toxicity and outcome; and considering all these background and observations, we studied the distribution of TSER, MTHFR C677T, p53 codon 72 and MDR1 C3435T gene polymorphisms in BC patients from Gran Canaria treated with neoadjuvant chemotherapy. Login to comment 64 ABCC8 p.Cys677Thr Genotyping Polymorphic sites in TYMS (TSER), MTHFR (C677T), p53 codon 72 (Arg/Pro) and MDR1 (C3435T) were examined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis as previously reported [26]. Login to comment 78 ABCC8 p.Cys677Thr TSER, MTHFR C677T, p53 Arg72Pro and MDR1 C3435T allelic and genotypic frequencies were estimated (Table 3). Login to comment 79 ABCC8 p.Cys677Thr Observed allelic frequencies were (%): TSER, (2) 54 and (3) 46; MTHFR C677T, (C) 59 and (T) 41; p53 Arg72Pro, (Arg) 73 and (Pro) 27; MDR1 C3435T, (C) 52 and (T) 48. Login to comment 90 ABCC8 p.Cys677Thr In univariate analysis, a significant association between adverse reactions and the polymorphisms MTHFR C677T and p53 codon 72 was established (Table 4). Login to comment 100 ABCC8 p.Cys677Thr n Genotypes (n, %) Alleles (n, %) TS 28bp STR 2/2 2/3 3/3 2 3 49 15 (31) 23 (47) 11 (22) 53 (54) 45 (46) MTHFR C677T C/C C/T T/T C T 50 16 (32) 27 (54) 7 (14) 59 (59) 41 (41) p53 codon72 Arg/Arg Arg/Pro Pro/Pro Arg Pro 50 26 (52) 21 (42) 3 (6) 73 (73) 27 (27) MDR1 C3435T C/C C/T T/T C T 50 14 (28) 24 (48) 12 (24) 52 (52) 48 (48) L.A. Henrı´quez-Herna´ndez et al. / Cancer Epidemiology 34 (2010) 634-638636 isms in toxicity due to chemotherapy. Login to comment 103 ABCC8 p.Cys677Thr Discussion We explored the distribution of TSER, MTHFR C677T, p53 Arg72Pro and MDR1 C3435T gene polymorphisms in breast cancer patients treated with neoadjuvant chemotherapy. Login to comment 104 ABCC8 p.Cys677Thr The appearance of adverse reactions was significantly associated with the polymorphisms MTHFR C677T and p53 codon 72. Login to comment 114 ABCC8 p.Cys677Thr MTHFR C677T has been shown to alter enzyme activity as well as 5-FU and MTX sensitivity [9,29]. Login to comment 117 ABCC8 p.Cys677Thr MTHFR C677T polymorphism appears to be an important predictor of CMF-related severe toxicity. Login to comment 119 ABCC8 p.Cys677Thr The C/C genotype of the MTHFR C677T polymorphism was protective against grade 3-4 toxicity in colorectal cancer patients [34]. Login to comment 122 ABCC8 p.Cys677Thr It has been suggested that MTHFR A1298C gene, but not C677T polymorphism is associated with MTX-related toxicity in children treated for acute lymphoblastic leukemia and non-Hodgkin lymphoma [35]. Login to comment 139 ABCC8 p.Cys677Thr We introduced new data related to the role of TSER, MTHFR C677T, p53 codon 72 and MDR1 C3435T in patients with breast cancer treated with neoadjuvant chemotherapy. Login to comment