Multiple Analytical Approaches Demonstrate a Complex Relationship of Genetic and Nongenetic Factors with Cisplatin- and Carboplatin-Induced Nephrotoxicity in Lung Cancer Patients

H. Eugene Liu, Kuan Jen Bai, Yu Chen Hsieh, Ming Chih Yu, Chun-Nin Lee, Jer Hua Chang, Han Lin Hsu, Pei Chih Lu, Hsiang Yin Chen

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
Article number937429
JournalBioMed Research International
Volume2014
DOIs
Publication statusPublished - 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Medicine(all)

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