当前位置： SCI文献检索 > Pharmacogenetics and Genomics期刊下所有文献 > A haplotype of the methylenetetrahydrofolate reductase gene predicts poor tumor response in rectal cancer patients receiving preoperative chemoradiation.

A haplotype of the methylenetetrahydrofolate reductase gene predicts poor tumor response in rectal cancer patients receiving preoperative chemoradiation.

Abstract：

OBJECTIVE:The objective of the present study was to evaluate whether germline methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms as well as polymorphisms in the thymidylate synthase gene promoter, namely the variable number tandem repeat polymorphism (TS VNTR) and the intrarepeat G to C single nucleotide polymorphism (TS SNP), are predictive markers of tumor regression in rectal cancer patients following preoperative chemoradiotherapy. BASIC METHODS:Blood samples from 125 patients with primary adenocarcinoma of the mid-low rectum who received 5-fluorouracil-based chemotherapy and external beam radiotherapy (median dose 48.4 Gy), 125 patients (women n=45, men n=80; median age 60 years, range 31-79 years) were genotyped. Response to preoperative treatment was evaluated employing the Tumor Regression Grade criteria. On the basis of the pathologic response, patients were classified as responders (TRG 1-2, n=48) and non-responders (TRG 3-5, n=74). Three patients were excluded because of insufficient data. MAIN RESULTS:Among the polymorphic variants examined, the MTHFR 677T-1298A haplotype was, upon univariate analysis, the only variable found associated with tumor regression (P=0.004). Moreover, at multivariate analysis, the MTHFR 677T-1298A haplotype was an independent predictor of tumor regression. Patients not carrying the MTHFR 677T-1298A haplotype (odds ratio 0.29, 95% confidence interval 0.13-0.64, P=0.002) displayed a higher response rate than patients with the MTHFR 677T-1298A haplotype. CONCLUSIONS:Unlike TS VNTR and SNP polymorphisms, MTHFR 677T-1298A haplotype in genomic DNA has the potential to be a predictive marker of tumor response in rectal cancer patients submitted to preoperative chemoradiotherapy.

journal_name

Pharmacogenet Genomics

journal_title

Pharmacogenetics and genomics

authors

Terrazzino S,Agostini M,Pucciarelli S,Pasetto LM,Friso ML,Ambrosi A,Lisi V,Leon A,Lise M,Nitti D

doi

10.1097/01.fpc.0000230412.89973.c0

subject

Has Abstract

pub_date

2006-11-01 00:00:00

pages

817-24

issue

eissn

1744-6872

issn

1744-6880

pii

01213011-200611000-00007

journal_volume

pub_type

临床试验,杂志文章

在线工具

A haplotype of the methylenetetrahydrofolate reductase gene predicts poor tumor response in rectal cancer patients receiving preoperative chemoradiation.