{"doi":"10.1016/j.jhep.2010.09.028","title":"Association of the hemochromatosis gene with pazopanib-induced transaminase elevation in renal cell carcinoma","abstract":null,"journal":"Journal of Hepatology","year":2011,"id":653951,"datarank":3.4404887571065177,"base_score":3.9512437185814275,"endowment":3.9512437185814275,"self_citation_contribution":0.5926865577872142,"citation_network_contribution":2.8478021993193035,"self_endowment_contribution":0.5926865577872142,"citer_contribution":2.8478021993193035,"corpus_percentile":null,"corpus_rank":null,"citation_count":51,"citer_count":47,"citers_with_citation_signal":40,"citers_with_endowment":40,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1706536,"name":"Brian H. Reck","orcid":null,"position":1,"is_corresponding":false},{"id":1706539,"name":"Vicki L. Goodman","orcid":null,"position":2,"is_corresponding":false},{"id":1706540,"name":"Zhengyu Xue","orcid":null,"position":3,"is_corresponding":false},{"id":1706541,"name":"Lingkang Huang","orcid":null,"position":4,"is_corresponding":false},{"id":605786,"name":"Michael R. Barnes","orcid":"0000-0003-1981-2220","position":5,"is_corresponding":false},{"id":257481,"name":"Beena Koshy","orcid":"0000-0002-9058-1392","position":6,"is_corresponding":false},{"id":88879,"name":"Colin F. Spraggs","orcid":null,"position":7,"is_corresponding":false},{"id":1706548,"name":"Vincent E. Mooser","orcid":null,"position":8,"is_corresponding":false},{"id":6120,"name":"Lon R. Cardon","orcid":null,"position":9,"is_corresponding":false},{"id":1706550,"name":"Lini N. Pandite","orcid":null,"position":10,"is_corresponding":false},{"id":1706533,"name":"Chun-Fang Xu","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Association of the hemochromatosis gene with pazopanib-induced transaminase elevation in renal cell carcinoma","abstract":"<h4>Background & aims</h4>Pazopanib has demonstrated clinical benefit in patients with advanced renal cell carcinoma (RCC) and is generally well tolerated. However, transaminase elevations have commonly been observed. This 2-stage study sought to identify genetic determinants of alanine transaminase (ALT) elevations in pazopanib-treated white patients with RCC.<h4>Methods</h4>Data from two separate clinical studies were used to examine the association of genetic polymorphisms with maximum on-treatment ALT levels.<h4>Results</h4>Of 6852 polymorphisms in 282 candidate genes examined in an exploratory dataset of 115 patients, 92 polymorphisms in 40 genes were significantly associated with ALT elevation (p<0.01). Two markers (rs2858996 and rs707889) in the HFE gene, which are not yet known to be associated with hemochromatosis, showed evidence for replication. Because of multiple comparisons, there was a 12% likelihood the replication occurred by chance. These two markers demonstrated strong linkage disequilibrium (r(2)=0.99). In the combined dataset, median (25-75th percentile) maximum ALT values were 1.2 (0.7-1.9), 1.1 (0.8-2.5), and 5.4 (1.9-7.6)×ULN for rs2858996 GG (n=148), GT (n=82), and TT (n=1 2) genotypes, respectively. All 12 TT patients had a maximum ALT>ULN, and 8 (67%) had ALT≥3×ULN. The odds ratio (95% CI) for ALT≥3×ULN for TT genotype was 39.7 (2.2-703.7) compared with other genotypes. As a predictor of ALT≥3×ULN, the TT genotype had a negative predictive value of 0.83 and positive predictive value of 0.67. No TT patients developed liver failure.<h4>Conclusions</h4>The rs2858996/rs707889 polymorphisms in the HFE gene may be associated with reversible ALT elevation in pazo-panib-treated patients with RCC.","is_dataset_classified":null,"base_score":3.9512437185814275,"endowment":3.9512437185814275,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"21145803","pmcid":null,"openalex_id":"https://openalex.org/W2069674339","authors":[],"funders":[],"total_grants":0,"fwci":3.0918,"citation_percentile":0.91509348,"influential_citations":0,"citation_trend":[{"year":2012,"count":5},{"year":2013,"count":3},{"year":2014,"count":5},{"year":2015,"count":3},{"year":2016,"count":4},{"year":2017,"count":6},{"year":2018,"count":6},{"year":2019,"count":6},{"year":2020,"count":4},{"year":2023,"count":1},{"year":2024,"count":1},{"year":2026,"count":1}],"oa_status":"closed","license":"https://www.elsevier.com/tdm/userlicense/1.0/","oa_locations":[{"url":"https://api.elsevier.com/content/article/PII:S0168827810009360?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0168827810009360?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.jhep.2010.09.028","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/21145803","host_type":"repository"},{"url":"https://iris.unil.ch/handle/iris/157389","host_type":"repository"},{"url":"https://serval.unil.ch/notice/serval:BIB_88E2F3B51D6F","host_type":"repository"}],"fields_of_study":["Renal cell carcinoma treatment","Ferroptosis and cancer prognosis","Hepatocellular Carcinoma Treatment and Prognosis","Aged","Alanine Transaminase","Angiogenesis Inhibitors","Antineoplastic Agents","Carcinoma, Renal Cell","Female","Genes, MHC Class I","Genes, MHC Class II","Genetic Markers","Hemochromatosis Protein","Histocompatibility Antigens Class I","Humans","Indazoles","Kidney Neoplasms","Male","Membrane Proteins","Middle Aged","Pharmacogenetics","Polymorphism, Single Nucleotide","Pyrimidines","Sulfonamides"],"mesh_terms":["Hemochromatosis Protein","Aged","Alanine Transaminase","Antineoplastic Agents","Carcinoma, Renal Cell","Female","Genes, MHC Class II","Genes, MHC Class I","Genetic Markers","Humans","Indazoles","Kidney Neoplasms","Male","Membrane Proteins","Middle Aged","Pharmacogenetics","Pyrimidines","Sulfonamides","Histocompatibility Antigens Class I","Angiogenesis Inhibitors","Polymorphism, Single Nucleotide"],"keywords":["Pazopanib","Medicine","Internal medicine","Transaminase","Elevation (ballistics)","Oncology","Hepatocellular carcinoma","Renal cell carcinoma","Carcinoma","Cancer research","Gastroenterology","Biology"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-11T02:21:48.504791Z","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":[]}