TLR-3 polymorphism is an independent prognostic marker for stage II colorectal cancer

Castro, F. A., Forsti, A., Buch, S., Kalthoff, H., Krauss, C., Bauer, M., Egberts, J., Schniewind, B., Broering, D. C., Schreiber, S., Schmitt, M., Hampe, J., Hemminki, K. and Schafmayer, C. (2011) TLR-3 polymorphism is an independent prognostic marker for stage II colorectal cancer European Journal of Cancer, 47 (8). pp. 1203-1210. DOI 10.1016/j.ejca.2010.12.011.

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Background: Clinicopathologic stage is still the main parameter to evaluate the prognosis of newly diagnosed colorectal cancer (CRC) patients. Although molecular markers have been suggested for follow up of treated CRC patients, their complete clinical application is still under evaluation. Materials and methods: To evaluate the association of immune-related genes with CRC prognosis and survival, a total of 19 single nucleotide polymorphisms (SNPs) were genotyped in 614 German patients within the Kiel cohort (POPGEN). Results: A promoter variant (rs1800872) in the Interleukin-10 (IL-10) gene was associated with an increased lymph node metastasis involvement odds ratio (OR) = 2.1, 95% confidence interval (CI) = 1.03-4.2, for carriers of the TT genotype. More importantly, among 582 followed up patients the SNP rs3775291 in the toll-like receptor 3 (TLR-3) gene was associated with CRC specific survival (150 events). Patients carrying the TT genotype had a 93% increased risk of death compared with the CC carriers hazard ratio (HR) = 1.93, 95% CI 1.14-3.281. The observed effect of the TLR-3 variant was restricted to stage II patients (HR = 4.14, 95% CI 1.24-13.84) and to patients who did not receive adjuvant therapy (HR = 3.2, 95% CI 1.4-7.7). Conclusions: Our results may provide additional candidates for risk assessment in stage II CRC patients for treatment decision. Further validation of the presented findings is warranted. (C) 2010 Elsevier Ltd. All rights reserved.

Document Type: Article
Keywords: Alimentary tract Variants Prognosis and survival toll-like receptor-3 nf-kappa-b colon-cancer survival chemotherapy inflammation association induction apoptosis promoter
Research affiliation: Kiel University
Refereed: Yes
DOI etc.: 10.1016/j.ejca.2010.12.011
ISSN: 0959-8049
Date Deposited: 01 Nov 2012 04:57
Last Modified: 23 Jan 2013 10:05

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