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Verfasst von:Gast, Andreas [VerfasserIn]   i
 Lorenzo Bermejo, Justo [VerfasserIn]   i
 Claus, Rainer [VerfasserIn]   i
 Brandt, Andreas [VerfasserIn]   i
 Weires, Marianne [VerfasserIn]   i
 Weber, Alexander N. R. [VerfasserIn]   i
 Plass, Christoph [VerfasserIn]   i
 Sucker, Antje [VerfasserIn]   i
 Hemminki, Kari [VerfasserIn]   i
 Schadendorf, Dirk [VerfasserIn]   i
 Kumar, Rajiv [VerfasserIn]   i
Titel:Association of inherited variation in Toll-like receptor genes with malignant melanoma susceptibility and survival
Verf.angabe:Andreas Gast, Justo Lorenzo Bermejo, Rainer Claus, Andreas Brandt, Marianne Weires, Alexander Weber, Christoph Plass, Antje Sucker, Kari Hemminki, Dirk Schadendorf, Rajiv Kumar
E-Jahr:2011
Jahr:September 9, 2011
Umfang:7 S.
Fussnoten:Gesehen am 08.08.2023
Titel Quelle:Enthalten in: PLOS ONE
Ort Quelle:San Francisco, California, US : PLOS, 2006
Jahr Quelle:2011
Band/Heft Quelle:6(2011), 9, Artikel-ID e24370, Seite 1-7
ISSN Quelle:1932-6203
Abstract:The family of Toll-like receptors (TLRs) is critical in linking innate and acquired immunity. Polymorphisms in the genes encoding TLRs have been associated with autoimmune diseases and cancer. We investigated the genetic variation of TLR genes and its potential impact on melanoma susceptibility and patient survival. The study included 763 cutaneous melanoma cases recruited in Germany and 736 matched controls that were genotyped for 47 single nucleotide polymorphisms (SNPs) in 8 TLR genes. The relationship between genotype, disease status and survival was investigated taking into account patient and tumor characteristics, and melanoma treatment. Analysis of 7 SNPs in TLR2, 7 SNPs in TLR3 and 8 SNPs in TLR4 showed statistically significant differences in distribution of inferred haplotypes between cases and controls. No individual polymorphism was associated with disease susceptibility except for the observed tendency for TLR2-rs3804099 (odds ratio OR = 1.15, 95% CI 0.99-1.34, p = 0.07) and TLR4-rs2149356 (OR = 0.85, 95% CI 0.73-1.00, p = 0.06). Both polymorphisms were part of the haplotypes associated with risk modulation. An improved overall survival (Hazard ratio HR 0.53, 95% CI 0.32-0.88) and survival following metastasis (HR 0.55, 95% CI 0.34-0.91) were observed in carriers of the variant allele (D299G) of TLR4-rs4986790. In addition various TLR2, TLR4 and TLR5 haplotypes were associated with increased overall survival. Our results point to a novel association between TLR gene variants and haplotypes with melanoma survival. Our data suggest a role for the D299G polymorphism in the TLR4 gene in overall survival and a potential link with systemic treatment at stage IV of the disease. The polymorphic amino acid residue, located in the ectodomain of TLR4, can have functional consequences.
DOI:doi:10.1371/journal.pone.0024370
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: https://doi.org/10.1371/journal.pone.0024370
 Volltext: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0024370
 DOI: https://doi.org/10.1371/journal.pone.0024370
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:Cancer risk factors
 Cutaneous melanoma
 Haplotypes
 Melanoma
 Metastasis
 Single nucleotide polymorphisms
 Toll-like receptors
 Variant genotypes
K10plus-PPN:1854653199
Verknüpfungen:→ Zeitschrift

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