{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:38:50Z","timestamp":1760240330841,"version":"build-2065373602"},"reference-count":52,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2019,5,10]],"date-time":"2019-05-10T00:00:00Z","timestamp":1557446400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Indonesia Endowment Fund for Education (LPDP)","award":["20161022049506"],"award-info":[{"award-number":["20161022049506"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Although previous research identified candidate genetic polymorphisms associated with cisplatin nephrotoxicity, varying outcome definitions potentially contributed to the variability in the effect size and direction of this relationship. We selected genetic variants that have been significantly associated with cisplatin-induced nephrotoxicity in more than one published study (SLC22A2 rs316019; ERCC1 rs11615 and rs3212986; ERCC2 rs1799793 and rs13181) and performed a replication analysis to confirm associations between these genetic polymorphisms and cisplatin nephrotoxicity using various outcome definitions. We included 282 germ cell testicular cancer patients treated with cisplatin from 2009\u20132014, aged &gt;17 years recruited by the Canadian Pharmacogenomics Network for Drug Safety. Nephrotoxicity was defined using four grading tools: (1) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 for acute kidney injury (AKI) or CTCAE-AKI; (2) adjusted cisplatin-induced AKI; (3) elevation of serum creatinine; and (4) reduction in the estimated glomerular filtration rate (eGFR). Significant associations were only found when using the CTCAE v4.03 definition: genotype CA of the ERCC1 rs3212986 was associated with decreased risk of cisplatin nephrotoxicity (ORadj = 0.24; 95% CI: 0.08\u20130.70; p = 0.009) compared to genotype CC. In contrast, addition of allele A at SLC22A2 rs316019 was associated with increased risk (ORadj = 4.41; 95% CI: 1.96\u20139.88; p &lt; 0.001) while genotype AC was associated with a higher risk of cisplatin nephrotoxicity (ORadj = 5.06; 95% CI: 1.69\u201315.16; p = 0.004) compared to genotype CC. Our study showed that different case definitions led to variability in the genetic risk ascertainment of cisplatin nephrotoxicity. Therefore, consensus on a set of clinically relevant outcome definitions that all such studies should follow is needed.<\/jats:p>","DOI":"10.3390\/genes10050364","type":"journal-article","created":{"date-parts":[[2019,5,13]],"date-time":"2019-05-13T03:57:07Z","timestamp":1557719827000},"page":"364","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Outcome Definition Influences the Relationship between Genetic Polymorphisms of ERCC1, ERCC2, SLC22A2 and Cisplatin Nephrotoxicity in Adult Testicular Cancer Patients"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1264-9558","authenticated-orcid":false,"given":"Zulfan","family":"Zazuli","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine, Amsterdam University Medical Centers, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"},{"name":"Department of Pharmacology-Clinical Pharmacy, School of Pharmacy, Bandung Institute of Technology, Bandung 40132, Indonesia"},{"name":"Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3512 JE Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1225-4740","authenticated-orcid":false,"given":"Leila S.","family":"Otten","sequence":"additional","affiliation":[{"name":"Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3512 JE Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3348-5855","authenticated-orcid":false,"given":"Britt I.","family":"Dr\u00f6gem\u00f6ller","sequence":"additional","affiliation":[{"name":"British Columbia Children\u2019s Hospital Research Institute, Vancouver, BC V5Z 4H4, Canada"},{"name":"Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC V6T 1Z4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mara","family":"Medeiros","sequence":"additional","affiliation":[{"name":"Nephrology Research Unit, Hospital Infantil de M\u00e9xico Federico G\u00f3mez, Mexico City 06720, Mexico"},{"name":"Departamento de Farmacolog\u00eda, Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City 04510, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jose G.","family":"Monzon","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Tom Baker Cancer Centre, Calgary, AB T2N 4N2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Galen E. B.","family":"Wright","sequence":"additional","affiliation":[{"name":"British Columbia Children\u2019s Hospital Research Institute, Vancouver, BC V5Z 4H4, Canada"},{"name":"Department of Medical Genetics, University of British Columbia, Vancouver, BC V6T 1Z4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian K.","family":"Kollmannsberger","sequence":"additional","affiliation":[{"name":"BC Cancer Agency and University of British Columbia, Vancouver, BC V6T 1Z4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philippe L.","family":"Bedard","sequence":"additional","affiliation":[{"name":"Princess Margaret Cancer Centre and University of Toronto, Toronto, ON M5S, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuo","family":"Chen","sequence":"additional","affiliation":[{"name":"Medical Oncology and Hematology, Department of Medicine, Princess Margaret Cancer Centre-University Health Network and University of Toronto, Toronto, ON M5S, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen A.","family":"Gelmon","sequence":"additional","affiliation":[{"name":"BC Cancer Agency and University of British Columbia, Vancouver, BC V6T 1Z4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"McGoldrick","sequence":"additional","affiliation":[{"name":"Pharmaceutical Outcomes Programme, BC Children\u2019s Hospital, Vancouver, BC V6H 3N1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abhijat","family":"Kitchlu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, University Health Network and University of Toronto, Toronto, ON M5S, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4579-4081","authenticated-orcid":false,"given":"Susanne J. H.","family":"Vijverberg","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Amsterdam University Medical Centers, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1560-1074","authenticated-orcid":false,"given":"Rosalinde","family":"Masereeuw","sequence":"additional","affiliation":[{"name":"Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3512 JE Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colin J. D.","family":"Ross","sequence":"additional","affiliation":[{"name":"British Columbia Children\u2019s Hospital Research Institute, Vancouver, BC V5Z 4H4, Canada"},{"name":"Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC V6T 1Z4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geoffrey","family":"Liu","sequence":"additional","affiliation":[{"name":"Medical Oncology and Hematology, Department of Medicine, Princess Margaret Cancer Centre-University Health Network and University of Toronto, Toronto, ON M5S, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4485-4054","authenticated-orcid":false,"given":"Bruce C.","family":"Carleton","sequence":"additional","affiliation":[{"name":"Pharmaceutical Outcomes Programme, BC Children\u2019s Hospital, Vancouver, BC V6H 3N1, Canada"},{"name":"Division of Translational Therapeutics, Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, BC V6T 1Z4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0414-3442","authenticated-orcid":false,"given":"Anke H.","family":"Maitland-van der Zee","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Amsterdam University Medical Centers, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,5,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.ejphar.2014.07.025","article-title":"Cisplatin in cancer therapy: Molecular mechanisms of action","volume":"740","author":"Dasari","year":"2014","journal-title":"Eur. J. Pharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.bulcan.2016.11.011","article-title":"50th anniversary of cisplatin","volume":"104","author":"Rancoule","year":"2017","journal-title":"Bull. Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1007\/s00038-013-0507-9","article-title":"Innovations in health care and mortality trends from five cancers in seven European countries between 1970 and 2005","volume":"59","author":"Hoffmann","year":"2014","journal-title":"Int. J. Public. Health"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"487","DOI":"10.7150\/ijms.8.487","article-title":"Adverse event profiles of platinum agents: Data mining of the public version of the FDA adverse event reporting system, AERS and reproducibility of clinical observations","volume":"8","author":"Sakaeda","year":"2011","journal-title":"Int. J. Med. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/S0270-9295(03)00089-5","article-title":"Cisplatin nephrotoxicity","volume":"23","author":"Arany","year":"2003","journal-title":"Semin. Nephrol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1038\/nrneph.2009.97","article-title":"Chemotherapy-associated renal dysfunction","volume":"5","author":"Sahni","year":"2009","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2670","DOI":"10.1093\/annonc\/mdx360","article-title":"Long-term toxicity of cisplatin in germ-cell tumor survivors","volume":"28","author":"Chovanec","year":"2017","journal-title":"Ann. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1016\/S0140-6736(00)02044-4","article-title":"Circulating plasma platinum more than 10 years after cisplatin treatment for testicular cancer","volume":"355","author":"Gietema","year":"2000","journal-title":"Lancet"},{"key":"ref_9","first-page":"5969","article-title":"Pharmacokinetics of cis-diamminedichloroplatinum(II) after administration in hypertonic saline","volume":"46","author":"Bajorin","year":"1986","journal-title":"Cancer Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1038\/sj.ki.5002786","article-title":"Cisplatin nephrotoxicity: Mechanisms and renoprotective strategies","volume":"73","author":"Pabla","year":"2008","journal-title":"Kidney Int."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s40620-017-0392-z","article-title":"Cisplatin nephrotoxicity: A review of the literature","volume":"31","author":"Manohar","year":"2018","journal-title":"J. Nephrol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/tpj.2009.45","article-title":"Genetic polymorphisms and the efficacy and toxicity of cisplatin-based chemotherapy in ovarian cancer patients","volume":"10","author":"Khrunin","year":"2010","journal-title":"Pharmacogenomics J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.2217\/pgs.11.93","article-title":"Pharmacogenetic analyses of cisplatin-induced nephrotoxicity indicate a renoprotective effect of ERCC1 polymorphisms","volume":"12","author":"Tzvetkov","year":"2011","journal-title":"Pharmacogenomics"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.1002\/cncr.26472","article-title":"Germline genetic polymorphisms may influence chemotherapy response and disease outcome in osteosarcoma: A pilot study","volume":"118","author":"Windsor","year":"2012","journal-title":"Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s12094-015-1343-6","article-title":"The relationship between polymorphisms of genes regulating DNA repair or cell division and the toxicity of platinum and vinorelbine chemotherapy in advanced NSCLC patients","volume":"18","author":"Powrozek","year":"2016","journal-title":"Clin. Transl. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1007\/s10157-012-0638-y","article-title":"Effects of genetic variants in SLC22A2 organic cation transporter 2 and SLC47A1 multidrug and toxin extrusion 1 transporter on cisplatin-induced adverse events","volume":"16","author":"Iwata","year":"2012","journal-title":"Clin. Exp. Nephrol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Zhang, L., Gao, G., Li, X., Ren, S., Li, A., Xu, J., Zhang, J., and Zhou, C. (2012). Association between single nucleotide polymorphisms (SNPs) and toxicity of advanced non-small-cell lung cancer patients treated with chemotherapy. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0048350"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1038\/clpt.2009.139","article-title":"Contribution of organic cation transporter 2 (OCT2) to cisplatin-induced nephrotoxicity","volume":"86","author":"Filipski","year":"2009","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.3389\/fphar.2018.01111","article-title":"Genetic Variations and Cisplatin Nephrotoxicity: A Systematic Review","volume":"9","author":"Zazuli","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2876","DOI":"10.1158\/1078-0432.CCR-06-2543","article-title":"Prospective assessment of XPD Lys751Gln and XRCC1 Arg399Gln single nucleotide polymorphisms in lung cancer","volume":"13","author":"Giachino","year":"2007","journal-title":"Clin. Cancer Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1056\/NEJMoa1214271","article-title":"ERCC1 isoform expression and DNA repair in non-small-cell lung cancer","volume":"368","author":"Friboulet","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1007\/s12032-017-0905-6","article-title":"Pharmacogenomics of platinum-based chemotherapy in non-small cell lung cancer: Focusing on DNA repair systems","volume":"34","author":"Xiong","year":"2017","journal-title":"Med. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"7643981","DOI":"10.1155\/2016\/7643981","article-title":"A Significant Statistical Advancement on the Predictive Values of ERCC1 Polymorphisms for Clinical Outcomes of Platinum-Based Chemotherapy in Non-Small Cell Lung Cancer: An Updated Meta-Analysis","volume":"2016","author":"Han","year":"2016","journal-title":"Dis. Markers"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2490","DOI":"10.3390\/toxins2112490","article-title":"Mechanisms of Cisplatin nephrotoxicity","volume":"2","author":"Miller","year":"2010","journal-title":"Toxins"},{"key":"ref_25","first-page":"4183","article-title":"Saving ears and kidneys from cisplatin","volume":"33","author":"Wensing","year":"2013","journal-title":"Anticancer Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s00439-008-0592-7","article-title":"Strengthening the reporting of genetic association studies (STREGA): An extension of the STROBE Statement","volume":"125","author":"Little","year":"2009","journal-title":"Hum. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1001\/jamaoncol.2017.0502","article-title":"Association Between SLC16A5 Genetic Variation and Cisplatin-Induced Ototoxic Effects in Adult Patients With Testicular Cancer","volume":"3","author":"Drogemoller","year":"2017","journal-title":"JAMA Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"604","DOI":"10.7326\/0003-4819-150-9-200905050-00006","article-title":"A new equation to estimate glomerular filtration rate","volume":"150","author":"Levey","year":"2009","journal-title":"Ann. Intern. Med."},{"key":"ref_29","first-page":"1","article-title":"KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease","volume":"3","author":"Group","year":"2013","journal-title":"Kidney Int. Suppl."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.2215\/CJN.02010408","article-title":"Associations of kidney function with cardiovascular medication use after myocardial infarction","volume":"3","author":"Winkelmayer","year":"2008","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1111\/bcpt.12376","article-title":"Association between Cardiovascular Drugs and Chronic Kidney Disease in Non-Institutionalized Elderly Patients","volume":"117","author":"Becquemont","year":"2015","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1097\/CRD.0b013e3180301b69","article-title":"Cardiovascular drug therapy in the elderly","volume":"15","author":"Aronow","year":"2007","journal-title":"Cardiol. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1097\/01.ASN.0000135121.81744.75","article-title":"Renal function, digoxin therapy and heart failure outcomes: Evidence from the digoxin intervention group trial","volume":"15","author":"Shlipak","year":"2004","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"S88","DOI":"10.1016\/j.jcjd.2017.10.034","article-title":"Pharmacologic Glycemic Management of Type 2 Diabetes in Adults","volume":"42","author":"Lipscombe","year":"2018","journal-title":"Can. J. Diabetes"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Awdishu, L., and Mehta, R.L. (2017). The 6R\u2019s of drug induced nephrotoxicity. BMC Nephrol., 18.","DOI":"10.1186\/s12882-017-0536-3"},{"key":"ref_36","unstructured":"BCCA Genitourinary Chemotherapy Protocols (2018, February 21). BC Cancer, Provincial Health Services Authority. Available online: http:\/\/www.bccancer.bc.ca\/health-professionals\/clinical-resources\/chemotherapy-protocols\/genitourinary#Testicular."},{"key":"ref_37","unstructured":"CCA Genitourinary Cancer Guidelines and Advice (2018, February 21). Cancer Care Ontario. Available online: https:\/\/www.cancercareontario.ca\/en\/guidelines-advice\/types-of-cancer\/genitourinary?f%5B0%5D=field_type_of_cancer%3A656&f%5B1%5D=field_type_of_cancer%3A681."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1038\/bjc.1994.87","article-title":"Comparative evaluation of cisplatin and carboplatin sensitivity in endometrial adenocarcinoma cell lines","volume":"69","author":"Rantanen","year":"1994","journal-title":"Br. J. Cancer"},{"key":"ref_39","unstructured":"(2018, February 15). Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. National Cancer Institute, Available online: https:\/\/evs.nci.nih.gov\/ftp1\/CTCAE\/About.html."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1634\/theoncologist.2011-0400","article-title":"Diagnosis and management of hyponatremia in cancer patients","volume":"17","author":"Castillo","year":"2012","journal-title":"Oncologist"},{"key":"ref_41","unstructured":"CPNDS (2019, January 08). Welcome to The Canadian Pharmacogenomics Network for Drug Safety (CPNDS). Available online: http:\/\/cpnds.ubc.ca\/."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1111\/jcpt.12097","article-title":"Absence of effect of SLC22A2 genotype on cisplatin-induced nephrotoxicity in oesophageal cancer patients receiving cisplatin and 5-fluorouracil: Report of results discordant with those of earlier studies","volume":"38","author":"Hinai","year":"2013","journal-title":"J. Clin. Pharm. Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"30","DOI":"10.2478\/v10039-011-0013-3","article-title":"Lack of correlation between ERCC1 (C8092A) single nucleotide polymorphism and efficacy\/toxicity of platinum based chemotherapy in Chinese patients with advanced non-small cell lung cancer","volume":"56","author":"KimCurran","year":"2011","journal-title":"Adv. Med. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2863","DOI":"10.1200\/JCO.2008.19.1718","article-title":"Pharmacogenetic analyses of a phase III trial in metastatic gastroesophageal adenocarcinoma with fluorouracil and leucovorin plus either oxaliplatin or cisplatin: A study of the arbeitsgemeinschaft internistische onkologie","volume":"27","author":"Goekkurt","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1093\/annonc\/mdr324","article-title":"The influence of platinum pathway polymorphisms on the outcome in patients with malignant mesothelioma","volume":"23","author":"Erculj","year":"2012","journal-title":"Ann. Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2289","DOI":"10.1016\/j.fct.2012.03.077","article-title":"Ameliorative effects of SLC22A2 gene polymorphism 808 G\/T and cimetidine on cisplatin-induced nephrotoxicity in Chinese cancer patients","volume":"50","author":"Zhang","year":"2012","journal-title":"Food Chem. Toxicol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1177\/096721090201000501","article-title":"The effect of age on serum creatinine levels in an aging population: relevance to vascular surgery","volume":"10","author":"Tiao","year":"2002","journal-title":"Cardiovasc. Surg."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2054358117690338","DOI":"10.1177\/2054358117690338","article-title":"Design and Methods of the Pan-Canadian Applying Biomarkers to Minimize Long-Term Effects of Childhood\/Adolescent Cancer Treatment (ABLE) Nephrotoxicity Study: A Prospective Observational Cohort Study","volume":"4","author":"McMahon","year":"2017","journal-title":"Can. J. Kidney Health Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1758","DOI":"10.1093\/carcin\/bgn067","article-title":"A distinct ERCC1 haplotype is associated with mRNA expression levels in prostate cancer patients","volume":"29","author":"Woelfelschneider","year":"2008","journal-title":"Carcinogenesis"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.ebiom.2018.03.003","article-title":"Functional Polymorphisms at ERCC1\/XPF Genes Confer Neuroblastoma Risk in Chinese Children","volume":"30","author":"Zhuo","year":"2018","journal-title":"EBioMedicine"},{"key":"ref_51","unstructured":"Consortium, G. (The Genotype-Tissue Expression (GTEx), 2017). The Genotype-Tissue Expression (GTEx)."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"119","DOI":"10.3109\/07853890.2010.549144","article-title":"Disposition of metformin: variability due to polymorphisms of organic cation transporters","volume":"44","author":"Zolk","year":"2012","journal-title":"Ann. Med."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/10\/5\/364\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:51:01Z","timestamp":1760187061000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/10\/5\/364"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,10]]},"references-count":52,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2019,5]]}},"alternative-id":["genes10050364"],"URL":"https:\/\/doi.org\/10.3390\/genes10050364","relation":{},"ISSN":["2073-4425"],"issn-type":[{"type":"electronic","value":"2073-4425"}],"subject":[],"published":{"date-parts":[[2019,5,10]]}}}