ABCMdb

PMID: 20371218

Henriquez-Hernandez LA, Perez LF, Hernandez AG, de Leon AC, Diaz-Chico B, Rosales AM
TYMS, MTHFR, p53 and MDR1 gene polymorphisms in breast cancer patients treated with adjuvant therapy.
Cancer Epidemiol. 2010 Aug;34(4):490-3. Epub 2010 Apr 3., [PubMed]

Sentences

No. Mutations Sentence Comment

13 ABCC8 p.Cys677Thr C677T is a common single nucleotide polymorphism (SNP) in exon 4 at the folate binding site of the MTHFR gene which results in alanine to valine substitution at codon 222 [10]. Login to comment 18 ABCC8 p.Cys677Thr Several studies in vivo and Cancer Epidemiology 34 (2010) 490-493 A R T I C L E I N F O Article history: Accepted 8 March 2010 Available online 3 April 2010 Keywords: Breast cancer Adjuvant chemotherapy Multifocal tumour Polymorphism PCR-RFLP Risk factors MTHFR A B S T R A C T Purpose: The distribution of TSER (TYMS), C677T (MTHFR), Arg72Pro (p53) and C3435T (MDR1) gene polymorphisms was investigated in 80 consecutive breast cancer patients treated with adjuvant chemotherapy. Login to comment 19 ABCC8 p.Cys677Thr Results: Observed allelic frequencies were: TSER, (2) 0.55 and (3) 0.45; MTHFR C677T, (C) 0.65 and (T) 0.35; p53 Arg72Pro, (Arg) 0.76 and (Pro) 0.24; MDR1 C3435T, (C) 0.51 and (T) 0.49. Login to comment 20 ABCC8 p.Cys677Thr MTHFR C677T was found to be a strong predictor of the presence of multifocal tumour (odds ratio, 4.1; 95% CI, 1.1-15.7; P = 0.035). Login to comment 34 ABCC8 p.Cys677Thr Considering all these background and observations, our purpose was to investigate the distribution of TSER, MTHFR C677T, p53 codon 72 and MDR1 C3435T gene polymorphisms in breast cancer patients treated with adjuvant chemotherapy. Login to comment 48 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. Login to comment 53 ABCC8 p.Cys677Thr Amplification of the DNA regions containing the polymorphic sites in TSER, MTHFR C677T, p53 codon 72 and MDR1 C3435T was made as previously reported [24]. Login to comment 72 ABCC8 p.Cys677Thr TSER, MTHFR C677T, p53 Arg72Pro and MDR1 C3435T genotypic and allelic frequencies were estimated (Table 2). Login to comment 73 ABCC8 p.Cys677Thr Observed allelic frequencies were (%): TSER, (2) 55 and (3) 45; MTHFR C677T, (C) 65 and (T) 35; p53 Arg72Pro, (Arg) 76 and (Pro) 24; MDR1 C3435T, (C) 51 and (T) 49. Login to comment 77 ABCC8 p.Cys677Thr We observed a significant association between MTHFR C677T polymorphism and the presence of multifocal lesions in the tumour. Login to comment 85 ABCC8 p.Cys677Thr Discussion We present here for the first time a significant association between MTHFR C677T polymorphism and the presence of multifocal lesions in the tumour. Login to comment 91 ABCC8 p.Cys677Thr Nonetheless, we observed a significant association between MTHFR C677T polymorphism and the presence of multifocal lesions in the tumour. Login to comment 93 ABCC8 p.Cys677Thr C677T gene polymorphism, which decreases enzyme activity, has been associated with cancer susceptibility [27]. Login to comment 97 ABCC8 p.Cys677Thr Finally, several studies have shown that MTHFR C677T polymorphism does not significantly contribute to the inherited genetic susceptibility to BC [27] and response to adjuvant therapy [28]. Login to comment 111 ABCC8 p.Cys677Thr ABCC8 p.Cys677Thr n Genotypic frequencies (n/%) Allelic frequencies (n/%) TS 28bp STR 2/2 2/3 3/3 2 3 79 26 (33) 35 (44) 18 (23) 87 (55) 71 (45) MTHFR C677T C/C C/T T/T C T 80 35 (44) 34 (42) 11 (14) 104 (65) 56 (35) p53 codon72 Arg/Arg Arg/Pro Pro/Pro Arg Pro 80 46 (58) 29 (36) 5 (6) 121 (76) 39 (24) MDR1 C3435T C/C C/T T/T C T 80 18 (23) 45 (56) 17 (21) 81 (51) 79 (49) Table 4 Logistic regression of MTHFR C677T variants and the presence of multifocal tumour in a multivariate analysis adjusted by age, BMI, menopause status, family history of BC, clinical stage, estrogen and progesterone receptor status and erbB2 expression. Login to comment 113 ABCC8 p.Cys677Thr category) MTHFR CC 4.1 (1.1-15.7) 0.035 Table 3 Association between MTHFR C677T gene polymorphism and the presence of multifocal tumour (x2 -test). Login to comment 117 ABCC8 p.Cys677Thr It has been reported that the protective effect of the homozygous variant TT form of the MTHFR genotype (C677T) on the risk of colorectal cancer seems to be modified by the level of methyl diets, that is, by folate [30]. Login to comment 122 ABCC8 p.Cys677Thr In conclusion, the distribution of TSER, MTHFR C677T, p53 Arg72Pro and MDR1 C3435T gene polymorphisms in BC patients treated with adjuvant chemotherapy was investigated. Login to comment 123 ABCC8 p.Cys677Thr We have shown that patients with the C/C variant of MTHFR C677T polymorphism suffer a four times higher risk of multifocal lesions in the tumour. Login to comment