Genetic variants in C-type lectin genes are associated with colorectal cancer susceptibility and clinical outcome

0396305 - ÚEM 2014 RIV DE eng J - Journal Article
Lu, S. - Bevier, M. - Huhn, S. - Sainz, J. - Lascorz, J. - Pardini, Barbara - Naccarati, Alessio - Vodičková, Ludmila - Novotný, J. - Hemminki, K. - Vodička, Pavel - Försti, A.
Genetic variants in C-type lectin genes are associated with colorectal cancer susceptibility and clinical outcome.
International Journal of Cancer. Roč. 133, č. 10 (2013), s. 2325-2333. ISSN 0020-7136. E-ISSN 1097-0215
R&D Projects: GA ČR GAP304/10/1286; GA ČR(CZ) GAP304/12/1585
Institutional support: RVO:68378041
Keywords : CD209 * colorectal cancer * polymorphism
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 5.007, year: 2013

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 tumors. Our study aimed to evaluate the correlation between polymorphisms in three C-type lectin genes, CD209, MBL2 and REG4, and colorectal cancer (CRC) risk and clinical outcome. We genotyped 15 potentially functional single nucleotide polymorphisms (SNPs) and assessed their associations with CRC risk in a case-control study of 1353 CRC cases and 767 healthy controls from the Czech Republic. We also analyzed these SNPs in relation to overall and event-free survival in 414 patients. 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 the 3'UTR SNP, rs7248637, had a decreased risk (OR 0.74, 95% CI 0.60-0.91). Multivariate survival analyses, including age, gender, TNM stage and grade, showed that patients without distant metastasis at the time of diagnosis and carrying the rs2994809 T allele had a decreased overall and event-free survival (HR 2.11, 95% CI 1.20-3.72 and HR 2.00, 95% CI 1.18-3.39, respectively). We show that SNPs in CD209 may affect CRC risk, while a SNP in REG4 may be a useful marker for CRC progression.
Permanent Link: http://hdl.handle.net/11104/0225229