{"doi":"10.17615/cbrq-qn24","title":"Methylenetetrahydrofolate reductase genetic polymorphisms and toxicity to 5-FU-based chemoradiation in rectal cancer","abstract":"Background:There is a large degree of variation in tumour response and host toxicities associated with neoadjuvant chemoradiation for rectal cancer patients. We performed a complimentary pharmacogenetic study to investigate germline polymorphisms of genes involved in 5-fluorouracil (5-FU) and irinotecan pathways and their potential association with clinical outcomes and toxicities from neoadjuvant chemoradiation in patients with rectal cancer treated in a prospective genotype-directed study.Methods:The germline DNA of 131 patients was genotyped for 10 variants in TYMS, MTHFR, DPYD, UGT1A1, ABCC1 and SLCO1B1 genes. Ninety-six patients were treated with 5-FU/radiotherapy (RT) and 35 received 5-FU/RT/irinotecan. Relationships between genetic variants and adverse events, tumour response, overall and disease-free survivals were assessed.Results:MTHFR 1298A>C and MTHFR diplotypes (for 677C>T and 1298A>C) were associated with chemoradiation-related toxicity when 5-FU was used alone. MTHFR haplotypes (677C–1298C) and diplotypes (CA–TA and TA–TA) showed, respectively, a protective and a negative effect on the incidence of severe diarrhoea or mucositis. No association was observed between genetic markers and drug response.Conclusion:MTHFR polymorphisms can potentially predict toxicity in patients treated with 5-FU as a single chemotherapeutic drug.","journal":"UNC Libraries","year":2020,"id":116323,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9594,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":544031,"name":"Fabienne Thomas","orcid":"0000-0001-9886-412X","position":1,"is_corresponding":false},{"id":544920,"name":"A. Alyasiri","orcid":null,"position":2,"is_corresponding":false},{"id":544921,"name":"J. W. Fleshman","orcid":null,"position":3,"is_corresponding":false},{"id":12629,"name":"Alison A. Motsinger‐Reif","orcid":"0000-0003-1346-2493","position":4,"is_corresponding":false},{"id":544922,"name":"R. J. Myerson","orcid":null,"position":5,"is_corresponding":false},{"id":141746,"name":"S. Roy","orcid":null,"position":6,"is_corresponding":false},{"id":544923,"name":"Anne Dvorak","orcid":null,"position":7,"is_corresponding":false},{"id":544924,"name":"B. R. Tan","orcid":null,"position":8,"is_corresponding":false},{"id":32979,"name":"Howard L. McLeod","orcid":"0000-0002-9004-9232","position":9,"is_corresponding":false},{"id":524584,"name":"Janelle M. Hoskins","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:13:44.286758Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}