{"doi":"10.17615/w0zc-fn45","title":"Functional","abstract":"BACKGROUND: We propose that single-nucleotide polymorphisms (SNPs) in genes of the vascular endothelial growth factor pathway of angiogenesis will associate with survival in non-small-cell lung cancer (NSCLC) patients. METHODS: Fifty-three SNPs in vascular endothelial growth factor-pathway genes were genotyped in 150 European stage I-III NSCLC patients and tested for associations with patient survival. Replication was performed in an independent cohort of 142 European stage I-III patients. Reporter gene assays were used to assess the effects of SNPs on transcriptional activity. RESULTS: In the initial cohort, five SNPs associated (q < 0.05) with relapse-free survival (RFS). The minor alleles of intronic FLT1 SNPs, rs7996030 and rs9582036, associated with reduced RFS (hazard ratio [HR] = 1.67 [95% confidence interval, CI, 1.22-2.29] and HR = 1.51 [95% CI, 1.14-2.01], respectively) and reduced transcriptional activity. The minor alleles of intronic KRAS SNPs, rs12813551 and rs10505980, associated with increased RFS (HR = 0.64 [0.46-0.87] and HR = 0.64 [0.47-0.87], respectively), and the minor allelic variant of rs12813551 also reduced transcriptional activity. Lastly, the minor allele of the intronic KRAS SNP rs10842513 associated with reduced RFS (HR = 1.65 [95% CI, 1.16-2.37]). Analysis of the functional variants suggests they are located in transcriptional enhancer elements. The negative effect of rs9582036 on RFS was confirmed in the replication cohort (HR = 1.69 [0.99-2.89], p = 0.028), and the association was significant in pooled analysis of both cohorts (HR = 1.67 [1.21-2.30], p = 0.0001). CONCLUSIONS: The functional FLT1 variant rs9582036 is a prognostic determinant of recurrence in stage I-III NSCLC. Its predictive value should be tested in the adjuvant setting of stage I-III NSCLC.","journal":"UNC Libraries","year":2020,"id":135895,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9115,"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":593412,"name":"Witold Rzyman","orcid":"0000-0002-9044-7791","position":1,"is_corresponding":false},{"id":594157,"name":"Todd Auman","orcid":null,"position":2,"is_corresponding":false},{"id":497761,"name":"Amy S. Etheridge","orcid":"0000-0002-1857-3486","position":3,"is_corresponding":false},{"id":593413,"name":"Osman Mirza","orcid":"0000-0001-9435-0690","position":4,"is_corresponding":false},{"id":593414,"name":"Jacek Jassem","orcid":"0000-0002-8875-6747","position":5,"is_corresponding":false},{"id":593415,"name":"Eloísa Jantus‐Lewintre","orcid":"0000-0001-7395-4380","position":6,"is_corresponding":false},{"id":346841,"name":"Kouros Owzar","orcid":"0000-0002-3340-1287","position":7,"is_corresponding":false},{"id":259627,"name":"Laia Paré","orcid":"0000-0002-4904-558X","position":8,"is_corresponding":false},{"id":436460,"name":"Federico Innocenti","orcid":"0000-0001-9247-979X","position":9,"is_corresponding":false},{"id":593416,"name":"Chen Jiang","orcid":"0000-0001-8336-6814","position":10,"is_corresponding":false},{"id":25345,"name":"William Zhang","orcid":"0000-0002-8850-5235","position":11,"is_corresponding":false},{"id":593417,"name":"Rafał Dziadziuszko","orcid":"0000-0001-8080-9843","position":12,"is_corresponding":false},{"id":593418,"name":"Carlos Camps","orcid":"0000-0002-0648-5403","position":13,"is_corresponding":false},{"id":593419,"name":"Daniel J. Crona","orcid":"0000-0003-3742-8863","position":14,"is_corresponding":false},{"id":226191,"name":"Fred R. Hirsch","orcid":"0000-0002-6885-1894","position":15,"is_corresponding":false},{"id":559341,"name":"Dylan M. Glubb","orcid":"0000-0002-2184-7708","position":16,"is_corresponding":false},{"id":594156,"name":"Eric Seiser","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:16:35.237665Z","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":[]}