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Background: Inflammatory responses play a vital role at different stages of colorectal carcinogenesis.C-type lectins mediate inflammatory/immune responses and participate in immune escape of pathogens and tnmors.Methods: We genotyped 15 potentially functional single nucleotide polymorphisms (SNPs) in three C-type lectin genes, CD209, MBL2 and REG4, and assessed their associations with CRC risk in a Czech case-control study of 1353 CRC cases and 767 healthy controls.We also analyzed these SNPs in relation to overall and event-free survival in 414 patients.Results: Three CD209 SNPs were associated with CRC risk.Minor allele carriers of the promoter SNP rs2287886 had an increased risk of CRC (OR 1.30, 95%CI 1.08-1.56), while minor allele carriers of two 3'UTR SNPs, rs7248637 and rs4804800, had a decreased risk (OR 0.74, 95%CI 0.60-0.91 and OR 0.81, 95%CI 0.66-1.00, respectively).Multivariate survival analyses showed that patients carrying either the REC4 rs2994809 T allele or the REG4 rs2994811 C allele had a significantly increased risk of death compared to the carriers of the wild-type genotype (HR 1.87, 95%CI 1.23-2.85 and HR 1.38, 95%CI 1.01-1.89, respectively).Carriers of the rs2994809 T allele also had a decreased event-free survival (HR 1.99, 95%CI 1.17-3.37).Conclusion: We show for the first time that SNPs in CD209 may affect CRC risk, while SNPs in REG4 may be useful markers for CRC progression.