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


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 1.14-3.28]. 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).


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.
Division of Molecular Genetic Epidemiology, German Cancer Research Center, DKFZ, Heidelberg, Germany.
F A
FA
Castro
A
A
Försti
S
S
Buch
H
H
Kalthoff
C
C
Krauss
M
M
Bauer
J
J
Egberts
B
B
Schniewind
D C
DC
Broering
S
S
Schreiber
M
M
Schmitt
J
J
Hampe
K
K
Hemminki
C
C
Schafmayer
D000368:Aged; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D005858:Germany; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011401:Promoter Regions, Genetic; D051196:Toll-Like Receptor 3 / Q000235:genetics*
C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D016753:Interleukin-10