IL28B polymorphism cannot predict response to interferon alpha treatment in patients with melanoma

• Published in: PloS one Vol. 9; no. 11; p. e112613
• Main Authors: Probst, Martin, Hoeller, Christoph, Ferenci, Peter, Staettermayer, Albert F, Beinhardt, Sandra, Pehamberger, Hubert, Kittler, Harald, Grabmeier-Pfistershammer, Katharina
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 12.11.2014; Public Library of Science (PLoS)
• Subjects: Aged; Biological products industry; Biological response modifiers; Biology and Life Sciences; Chronic infection; Cytokines; Deoxyribonucleic acid; Dermatology; Development and progression; Disease Progression; Disease-Free Survival; DNA; Drug dosages; Drug therapy; Female; Gastroenterology; Gene expression; Gene polymorphism; Genetic aspects; Genetic Association Studies; Genome-wide association studies; Genomes; Genomics; Genotype; Genotype & phenotype; Health aspects; Hepatitis; Hepatitis C; Hepatology; Humans; Immunology; Infections; Infectious diseases; Interferon; Interferon alpha; Interferon-alpha - therapeutic use; Interferons; Interleukins - genetics; Internal medicine; Localization; Lymphatic system; Lymphocytes; Male; Medical research; Medicine and Health Sciences; Melanoma; Melanoma - drug therapy; Melanoma - genetics; Melanoma - pathology; Middle Aged; Multivariate analysis; Patients; Pharmacogenetics; Polymorphism; Polymorphism, Single Nucleotide; Prognosis; Retrospective Studies; Risk analysis; Risk factors; Signal transduction; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Skin Neoplasms - drug therapy; Skin Neoplasms - genetics; Skin Neoplasms - pathology; Statistical analysis; Survival; Therapy; Treatment Outcome; α-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0112613

Recent genome-wide association studies revealed the rs12979860 single nucleotide polymorphism (SNP) of the IL28B gene (CC genotype) to be the strongest pre-therapeutic predictor of therapy response to interferon alpha in patients with chronic hepatitis C infection. The favorable CC genotype is associated with significantly higher rates of sustained virologic response. No data exist on the role of IL28B polymorphism in interferon therapy of diseases other than viral hepatitis. A retrospective study involving 106 patients with melanoma who received low- or high-dose interferon therapy was performed. The CC and non-CC genotype of IL28B rs12979860 SNP were correlated with progression-free and overall survival. 44 (41.5%) patients were CC and 62 (58.5%) non-CC. There was no statistically significant difference in age at diagnosis, melanoma type or localization, Breslow level or AJCC stage between CC and non-CC patients. During the observation period (6.43±4.66 years) disease progression occurred in 36 (34%) patients after 5.5±4.3 years. 43.2% (19) of patients with CC and 27.4% (17) of patients with non-CC genotype were affected (p = 0.091). Disease progression was more frequent in patients on high dose interferon therapy and with a worse AJCC stage. In contrast to classical risk factors like tumor thickness and clinical stage, IL28B polymorphism was not associated with progression-free or overall survival in patients with melanoma treated with interferon alpha.