This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services 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 Liu, D. Articles by Weber, J. Search for Related Content PubMed PubMed Citation Articles by Liu, D. Articles by Weber, J.

Impact of Gene Polymorphisms on Clinical Outcome for Stage IV Melanoma Patients Treated with Biochemotherapy: An Exploratory Study

Departments of ¹ Medicine and ² Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, California and ³ Divisions of Medical and Surgical Oncology and ⁴ Weil Medical Oncology Research Laboratory, John Wayne Cancer Institute at St. John's Health Center, Santa Monica, California

Requests for reprints: Jeffrey Weber, Department of Medicine, University of Southern California Keck School of Medicine/Norris Cancer Center, 1441 Eastlake Avenue, Los Angeles, CA 90033. Phone: 323-865-3360; Fax: 323-865-0061; E-mail: jweber{at}usc.edu.

Purpose: Biochemotherapy can achieve high response rates in advanced melanoma, but the factors that influence regression and survival remain unknown. The present exploratory study tested the hypothesis that cytokine gene polymorphisms predict clinical outcome in stage IV melanoma patients treated with biochemotherapy.

Experimental Design: Ninety patients with stage IV melanoma were treated with biochemotherapy, including cisplatin, vinblastine, and dacarbazine combined with interleukin (IL)-2 and IFN- either with or without tamoxifen. Cytokine gene polymorphisms for IFN- (+874AT) and IL-10 (–1082GA) were assessed. X-ray repair cross-complementing gene 1 (XRCC1; Arg399Gln), xeroderma pigmentosum complementary group D (XPD; Lys751Gln), and excision repair cross-complementing gene 1 (ERCC1; codon 118) DNA repair polymorphisms were also determined.

Results: IFN- (+874AT) gene polymorphism was statistically significantly associated with response (P = 0.001), progression-free survival (P = 0.0012), and overall survival (P < 0.001), whereas the IL-10 polymorphism was marginally associated with response (P = 0.03) and overall survival (P = 0.065). Multivariate analysis revealed that IFN- (+874AT) independently predicted overall survival (P = 0.003). The ERCC1 polymorphism was weakly associated with overall survival (P = 0.045). Combining polymorphisms for IFN-, IL-10, and ERCC1 stratified patients into four distinct groups with significantly different clinical outcome (P < 0.001), so that patients with more "favorable" polymorphisms had a better outcome.

Conclusions: Cytokine gene polymorphisms predicted clinical outcome for advanced melanoma patients who received biochemotherapy. The combined effects of multiple genetic polymorphisms may provide more accurate prognostic information. Additional independent studies are needed to confirm these pilot findings.

Key Words: gene • DNA repair • cytokine

This article has been cited by other articles:

				C. Li, Z. Hu, Z. Liu, L.-E Wang, S. S. Strom, J. E. Gershenwald, J. E. Lee, M. I. Ross, P. F. Mansfield, J. N. Cormier, et al. Polymorphisms in the DNA Repair Genes XPC, XPD, and XPG and Risk of Cutaneous Melanoma: a Case-Control Analysis Cancer Epidemiol. Biomarkers Prev., December 1, 2006; 15(12): 2526 - 2532. [Abstract] [Full Text] [PDF]

				S.-J. He, G. Stevens, A. W. Braithwaite, and M. R. Eccles Transfection of melanoma cells with antisense PAX3 oligonucleotides additively complements cisplatin-induced cytotoxicity Mol. Cancer Ther., June 1, 2005; 4(6): 996 - 1003. [Abstract] [Full Text] [PDF]