Trial reportCancer2014
Polymorphisms in folate-metabolizing enzymes and response to 5-fluorouracil among patients with stage II or III rectal cancer (INT-0144; SWOG 9304).
Trial report in Cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 2 of them syntheses that pooled it.
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Who cites it
10 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Methylenetetrahydrofolate reductase polymorphisms and colorectal cancer prognosis: A meta-analysis.The journal of gene medicine · 2019Pooled it
- Associations between genetic polymorphisms of membrane transporter genes and prognosis after chemotherapy: meta-analysis and finding from Seoul Breast Cancer Study (SEBCS).The pharmacogenomics journal · 2018Pooled it
- Polymorphisms of MTHFR C677T and A1298C associated with survival in patients with colorectal cancer treated with 5-fluorouracil-based chemotherapy.International journal of clinical oncology · 2017Trial
- Mutation and Microsatellite Instability (MSI) Affect the Differential Gene Expression of Folic Acid and 5-Flourouracil Metabolism-Related Genes in Colorectal Carcinoma.Current oncology (Toronto, Ont.) · 2025Article
- Methylenetetrahydrofolate reductase polymorphic variants C677T and A1298C in rectal cancer in Slavic population: significance for cancer risk and response to chemoradiotherapy.Frontiers in genetics · 2023Article
- Germline and Somatic Pharmacogenomics to Refine Rectal Cancer Patients Selection for Neo-Adjuvant Chemoradiotherapy.Frontiers in pharmacology · 2020Review
- Pathway analysis of genetic variants in folate-mediated one-carbon metabolism-related genes and survival in a prospectively followed cohort of colorectal cancer patients.Cancer medicine · 2018Article
- Individualized predictive signatures for 5-fluorouracil-based chemotherapy in right- and left-sided colon cancer.Cancer science · 2018Article
- Pharmacogenetics Biomarkers and Their Specific Role in Neoadjuvant Chemoradiotherapy Treatments: An Exploratory Study on Rectal Cancer Patients.International journal of molecular sciences · 2016Article
- Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
backgroundRecurrence and toxicity occur commonly among patients with rectal cancer who are treated with 5-fluorouracil (5-FU). The authors hypothesized that genetic variation in folate-metabolizing genes could play a role in interindividual variability. The objective of the current study was to evaluate the associations between genetic variants in folate-metabolizing genes and clinical outcomes among patients with rectal cancer treated with 5-FU.
methodsThe authors investigated 8 functionally significant polymorphisms in 6 genes (methylenetetrahydrofolate reductase [MTHFR] [C677T, A1298C], SLC19A1 [G80A], SHMT1 [C1420T], dihydrofolate reductase [DHFR] [Del19bp], TS 1494del,and TSER) involved in folate metabolism in 745 patients with TNM stage II or III rectal cancer enrolled in a phase 3 adjuvant clinical trial of 3 regimens of 5-FU and radiotherapy (INT-0144 and SWOG 9304).
resultsThere were no statistically significant associations noted between polymorphisms in any of the genes and overall survival, disease-free survival (DFS), and toxicity in the overall analyses. Nevertheless, there was a trend toward worse DFS among patients with the variant allele of MTHFR C677T compared with wild-type, particularly in treatment arm 2, in which patients with the MTHFR C677T TT genotype had worse overall survival (hazards ratio, 1.76; 95% confidence interval, 1.06-2.93 [P = .03]) and DFS (hazards ratio, 1.84; 95% confidence interval, 1.12-3.03 [P = .02]) compared with those with homozygous wild-type. In addition, there was a trend toward reduced hematological toxicity among patients with variants of SLC19A1 G80A in treatment arm 1 (P for trend, .06) and reduced esophagitis/stomatitis noted among patients with variants of TSER in treatment arm 3 (P for trend, .06).
conclusionsGenetic variability in folate-metabolizing enzymes was found to be associated only to a limited degree with clinical outcomes among patients with rectal cancer treated with 5-FU.
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