TLR-3 polymorphism is an independent prognostic marker for stage II colorectal cancer |
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Authors: | Castro F A Försti A Buch S Kalthoff H Krauss C Bauer M Egberts J Schniewind B Broering D C Schreiber S Schmitt M Hampe J Hemminki K Schafmayer C |
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Affiliation: | a Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany b Division of Genome Modifications and Carcinogenesis, German Cancer Research Center (DKFZ), Heidelberg, Germany c Center for Primary Health Care Research, Clinical Research Center, Lund University, Malmö, Sweden d POPGEN Biobank Project, Christian-Albrechts-University, Kiel, Germany e Department of General Internal Medicine, Christian-Albrechts-University, Kiel, Germany f Department of General and Thoracic Surgery, Christian-Albrechts-University, Kiel, Germany g Institute for Experimental Cancer Research/Comprehensive Cancer Center North, Christian-Albrechts-University, Kiel, Germany |
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Abstract: | BackgroundClinicopathologic 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 methodsTo 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).ResultsA 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 1.14-3.28]. 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).ConclusionsOur results may provide additional candidates for risk assessment in stage II CRC patients for treatment decision. Further validation of the presented findings is warranted. |
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Keywords: | Alimentary tract Variants Prognosis and survival |
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