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

Lu, Shun; Bevier, Melanie; Huhn, Stefanie; Sainz, Juan; Lascorz, Jesus; Pardini, Barbara; Naccarati, Alessio; Vodickova, Ludmila; Novotny, Jan and Hemminki, Kari LU , et al. (2013) In International Journal of Cancer 133(10). p.2325-2333
Abstract
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. Two CD209 SNPs were associated with CRC risk after adjustment for... (More)
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. Two CD209 SNPs were associated with CRC risk after adjustment for multiple comparison. 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 3UTR 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. What's new? The identification of new risk and prognostic biomarkers brings the prospect of individualized medicine ever closer. That promise is illustrated here, with the discovery of novel genetic variants in three C-type lectin genes, CD209, MBL2, and REG4, which previously have been implicated in colorectal carcinogenesis and prognosis. Genotyping of 15 C-type lectin single nucleotide polymorphisms uncovered a total of 34 variants in regulatory and coding regions of the three genes. Variants in two of the genes, CD209 and REG4, were linked to colorectal cancer risk and prognosis, respectively, suggesting that they may be of clinical value. (Less)
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publication status
published
subject
keywords
CD209, colorectal cancer, MBL, polymorphism, REG4
in
International Journal of Cancer
volume
133
issue
10
pages
2325 - 2333
publisher
John Wiley & Sons
external identifiers
  • wos:000324072300007
  • scopus:84883769767
ISSN
0020-7136
DOI
10.1002/ijc.28251
language
English
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yes
id
b68543ff-46d4-434d-8815-0e5c9f774984 (old id 4106221)
date added to LUP
2013-11-07 14:21:11
date last changed
2019-05-19 03:25:03
@article{b68543ff-46d4-434d-8815-0e5c9f774984,
  abstract     = {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. Two CD209 SNPs were associated with CRC risk after adjustment for multiple comparison. 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 3UTR 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. What's new? The identification of new risk and prognostic biomarkers brings the prospect of individualized medicine ever closer. That promise is illustrated here, with the discovery of novel genetic variants in three C-type lectin genes, CD209, MBL2, and REG4, which previously have been implicated in colorectal carcinogenesis and prognosis. Genotyping of 15 C-type lectin single nucleotide polymorphisms uncovered a total of 34 variants in regulatory and coding regions of the three genes. Variants in two of the genes, CD209 and REG4, were linked to colorectal cancer risk and prognosis, respectively, suggesting that they may be of clinical value.},
  author       = {Lu, Shun and Bevier, Melanie and Huhn, Stefanie and Sainz, Juan and Lascorz, Jesus and Pardini, Barbara and Naccarati, Alessio and Vodickova, Ludmila and Novotny, Jan and Hemminki, Kari and Vodicka, Pavel and Försti, Asta},
  issn         = {0020-7136},
  keyword      = {CD209,colorectal cancer,MBL,polymorphism,REG4},
  language     = {eng},
  number       = {10},
  pages        = {2325--2333},
  publisher    = {John Wiley & Sons},
  series       = {International Journal of Cancer},
  title        = {Genetic variants in C-type lectin genes are associated with colorectal cancer susceptibility and clinical outcome},
  url          = {http://dx.doi.org/10.1002/ijc.28251},
  volume       = {133},
  year         = {2013},
}