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BioMed Research International
Volume 2014, Article ID 937429, 9 pages
http://dx.doi.org/10.1155/2014/937429
Research Article

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

1Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, 111 Hsing-Long Road, Section 3, Taipei 116, Taiwan
2Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan
3Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan
4Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, 291 Jhongjheng Road, Jhonghe District, New Taipei City 235, Taiwan
5Department of Pharmacy, Wan Fang Hospital, Taipei Medical University, 111 Hsing-Long Road, Section 3, Taipei 116, Taiwan

Received 24 April 2014; Revised 9 July 2014; Accepted 17 July 2014; Published 28 August 2014

Academic Editor: Emmanuel A. Burdmann

Copyright © 2014 H. Eugene Liu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.