This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dolan, M. E. Articles by Badner, J. A. Search for Related Content PubMed PubMed Citation Articles by Dolan, M. E. Articles by Badner, J. A.

Heritability and Linkage Analysis of Sensitivity to Cisplatin-Induced Cytotoxicity

Departments of ¹ Medicine, ² Pediatrics, ³ Psychiatry, and ⁴ Human Genetics, and ⁵ Committee on Clinical Pharmacology and Pharmacogenomics, University of Chicago, Chicago, Illinois

Little is known about the genetic determinants explaining variation in sensitivity to chemotherapeutic cytotoxicity. We characterized the degree of cisplatin sensitivity, using lymphoblastoid cell lines derived from 10 Centre d’Etude du Polymorphisme Humain pedigrees. We estimated the heritability for susceptibility to cisplatin-induced cytotoxicity to be 0.47; therefore, sensitivity to the cytotoxic effects of cisplatin is under appreciable genetic influence. Linkage analysis was performed, and the strongest signal (lod score, 2.16; empirical P = 0.0005) was found on chromosome 1 at 44 cM. Susceptibility to cisplatin-induced cytotoxicity is likely due to multiple loci, with low locus-specific heritability contributing to the trait. These data show the power of using large pedigrees that have been extensively genotyped for evaluating the genetic contribution to sensitivity to cell growth inhibition by anticancer agents.

This article has been cited by other articles:

				R. S. Huang and M. J. Ratain Pharmacogenetics and pharmacogenomics of anticancer agents CA Cancer J Clin, January 1, 2009; 59(1): 42 - 55. [Abstract] [Full Text] [PDF]

				R. S. Huang, S. Duan, E. O. Kistner, W. K. Bleibel, S. M. Delaney, D. L. Fackenthal, S. Das, and M. E. Dolan Genetic Variants Contributing to Daunorubicin-Induced Cytotoxicity Cancer Res., May 1, 2008; 68(9): 3161 - 3168. [Abstract] [Full Text] [PDF]

				N. Pottier, M. H. Cheok, W. Yang, M. Assem, L. Tracey, J. C. Obenauer, J. C. Panetta, M. V. Relling, and W. E. Evans Expression of SMARCB1 modulates steroid sensitivity in human lymphoblastoid cells: identification of a promoter snp that alters PARP1 binding and SMARCB1 expression Hum. Mol. Genet., October 1, 2007; 16(19): 2261 - 2271. [Abstract] [Full Text] [PDF]

				R. S. Huang, S. Duan, W. K. Bleibel, E. O. Kistner, W. Zhang, T. A. Clark, T. X. Chen, A. C. Schweitzer, J. E. Blume, N. J. Cox, et al. A genome-wide approach to identify genetic variants that contribute to etoposide-induced cytotoxicity PNAS, June 5, 2007; 104(23): 9758 - 9763. [Abstract] [Full Text] [PDF]

				S. Duan, W. K. Bleibel, R. S. Huang, S. J. Shukla, X. Wu, J. A. Badner, and M. E. Dolan Mapping Genes that Contribute to Daunorubicin-Induced Cytotoxicity Cancer Res., June 1, 2007; 67(11): 5425 - 5433. [Abstract] [Full Text] [PDF]

				L. B. Travis, C. S. Rabkin, L. M. Brown, J. M. Allan, B. P. Alter, C. B. Ambrosone, C. B. Begg, N. Caporaso, S. Chanock, A. DeMichele, et al. Cancer Survivorship--Genetic Susceptibility and Second Primary Cancers: Research Strategies and Recommendations J Natl Cancer Inst, January 4, 2006; 98(1): 15 - 25. [Abstract] [Full Text] [PDF]

				R. A. Walgren, M. A. Meucci, and H. L. McLeod Pharmacogenomic Discovery Approaches: Will the Real Genes Please Stand Up? J. Clin. Oncol., October 10, 2005; 23(29): 7342 - 7349. [Abstract] [Full Text] [PDF]