title: Multiple analytical approaches demonstrate a complex relationship of genetic and nongenetic factors with cisplatin- and carboplatin-induced nephrotoxicity in lung cancer patients.
abstract: BACKGROUND
  Cisplatin and carboplatin cause nephrotoxicity by forming platinum-DNA adducts and lead to cell death.
  
  
  METHODS
  One-hundred and sixteen Taiwanese lung cancer patients who received cisplatin or carboplatin more than twice were recruited, and their genotypes were determined. The risk of renal dysfunction, injury to the kidney, failure of kidney function, loss of kidney function, and end-stage kidney disease (RIFLE) criteria were used to evaluate the occurrence of nephrotoxicity. A logistic regression, multiple regression with a classification and regression tree (CART), and the Framingham study risk score were used to analyze interactions between genetic and nongenetic factors in producing platinum-induced nephrotoxicity.
  
  
  RESULTS
  ERCC1 118C and TP53 72Arg polymorphisms were associated with increased risks of platinum-induced nephrotoxicity. Other risk factors found included the platinum type, baseline serum creatinine (Scr), coadministration of vinorelbine, and the number of chemotherapy cycles. The overall prediction rate of the CART was 82.7%, with a sensitivity of 0.630 and specificity of 0.896. The Framingham study risk prediction model contained 7 factors. Its prediction rate was 84.5%, with a sensitivity of 0.643 and specificity of 0.909.
  
  
  CONCLUSIONS
  Genetic polymorphisms of ERCC1 and TP53 are risk factors for nephrotoxicity. The CART analysis may provide a clinically applicable model to predict the risk of cisplatin- and carboplatin-induced nephrotoxicity.
authors.affiliation: Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, 111 Hsing-Long Road, Section 3, Taipei 116, Taiwan ; Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan.
authors.forename: H Eugene
authors.initials: HE
authors.lastname: Liu
authors.affiliation: Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, 111 Hsing-Long Road, Section 3, Taipei 116, Taiwan.
authors.forename: Kuan-Jen
authors.initials: KJ
authors.lastname: Bai
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan.
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Hsieh
authors.affiliation: Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, 111 Hsing-Long Road, Section 3, Taipei 116, Taiwan.
authors.forename: Ming-Chih
authors.initials: MC
authors.lastname: Yu
authors.affiliation: Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, 291 Jhongjheng Road, Jhonghe District, New Taipei City 235, Taiwan.
authors.forename: Chun-Nin
authors.initials: CN
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, 111 Hsing-Long Road, Section 3, Taipei 116, Taiwan.
authors.forename: Jer-Hua
authors.initials: JH
authors.lastname: Chang
authors.affiliation: Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, 111 Hsing-Long Road, Section 3, Taipei 116, Taiwan.
authors.forename: Han-Lin
authors.initials: HL
authors.lastname: Hsu
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan.
authors.forename: Pei-Chih
authors.initials: PC
authors.lastname: Lu
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan ; Department of Pharmacy, Wan Fang Hospital, Taipei Medical University, 111 Hsing-Long Road, Section 3, Taipei 116, Taiwan.
authors.forename: Hsiang-Yin
authors.initials: HY
authors.lastname: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D016190:Carboplatin / Q000627:therapeutic use*; D002648:Child; D002945:Cisplatin / Q000627:therapeutic use*; D015897:Comorbidity; D003404:Creatinine / Q000097:blood; D004268:DNA-Binding Proteins / Q000235:genetics*; D003627:Data Interpretation, Statistical; D064420:Drug-Related Side Effects and Adverse Reactions / Q000097:blood / Q000453:epidemiology / Q000235:genetics; D004720:Endonucleases / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D015994:Incidence; D007674:Kidney Diseases / Q000097:blood / Q000453:epidemiology* / Q000235:genetics*; D008171:Lung Diseases / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011379:Prognosis; D016016:Proportional Hazards Models; D018570:Risk Assessment / Q000379:methods; D017678:Sex Distribution; D013624:Taiwan / Q000453:epidemiology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D003404:Creatinine; D016190:Carboplatin; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin