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Single nucleotide polymorphisms within MUC4 are associated with colorectal cancer survival
S. Lu, C. Catalano, S. Huhn, B. Pardini, L. Partu, V. Vymetalkova, L. Vodickova, M. Levy, T. Buchler, K. Hemminki, P. Vodicka, A. Försti,
Language English Country United States
Document type Journal Article, Research Support, Non-U.S. Gov't
Grant support
NV15-27580A
MZ0
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Digital library NLK
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- MeSH
- Progression-Free Survival MeSH
- Adult MeSH
- Genotype MeSH
- Glycosylation MeSH
- Polymorphism, Single Nucleotide genetics MeSH
- Kaplan-Meier Estimate MeSH
- Colorectal Neoplasms genetics mortality pathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Mucin-4 genetics metabolism MeSH
- Mucins genetics metabolism MeSH
- Biomarkers, Tumor genetics MeSH
- Colonic Neoplasms genetics mortality pathology MeSH
- Disease-Free Survival MeSH
- Risk Factors MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Case-Control Studies MeSH
- Linkage Disequilibrium MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Czech Republic MeSH
Mucins and their glycosylation have been suggested to play an important role in colorectal carcinogenesis. We examined potentially functional genetic variants in the mucin genes or genes involved in their glycosylation with respect to colorectal cancer (CRC) risk and clinical outcome. We genotyped 23 single nucleotide polymorphisms (SNPs) covering 123 SNPs through pairwise linkage disequilibrium (r2>0.80) in the MUC1, MUC2, MUC4, MUC5AC, MUC6, and B3GNT6 genes in a hospital-based case-control study of 1532 CRC cases and 1108 healthy controls from the Czech Republic. We also analyzed these SNPs in relation to overall survival and event-free survival in a subgroup of 672 patients. Among patients without distant metastasis at the time of diagnosis, two MUC4 SNPs, rs3107764 and rs842225, showed association with overall survival (HR 1.40, 95%CI 1.08-1.82, additive model, log-rank p = 0.004 and HR 0.64, 95%CI 0.42-0.99, recessive model, log-rank p = 0.01, respectively) and event-free survival (HR 1.31, 95%CI 1.03-1.68, log-rank p = 0.004 and HR 0.64, 95%CI 0.42-0.96, log-rank p = 0.006, respectively) after adjustment for age, sex and TNM stage. Our data suggest that genetic variation especially in the transmembrane mucin gene MUC4 may play a role in the survival of CRC and further studies are warranted.
Department of Oncology Thomayer Hospital Prague Czech Republic
Division of Molecular Genetic Epidemiology German Cancer Research Center Heidelberg Germany
References provided by Crossref.org
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- $a Lu, Shun $u Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany. Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
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- $a Mucins and their glycosylation have been suggested to play an important role in colorectal carcinogenesis. We examined potentially functional genetic variants in the mucin genes or genes involved in their glycosylation with respect to colorectal cancer (CRC) risk and clinical outcome. We genotyped 23 single nucleotide polymorphisms (SNPs) covering 123 SNPs through pairwise linkage disequilibrium (r2>0.80) in the MUC1, MUC2, MUC4, MUC5AC, MUC6, and B3GNT6 genes in a hospital-based case-control study of 1532 CRC cases and 1108 healthy controls from the Czech Republic. We also analyzed these SNPs in relation to overall survival and event-free survival in a subgroup of 672 patients. Among patients without distant metastasis at the time of diagnosis, two MUC4 SNPs, rs3107764 and rs842225, showed association with overall survival (HR 1.40, 95%CI 1.08-1.82, additive model, log-rank p = 0.004 and HR 0.64, 95%CI 0.42-0.99, recessive model, log-rank p = 0.01, respectively) and event-free survival (HR 1.31, 95%CI 1.03-1.68, log-rank p = 0.004 and HR 0.64, 95%CI 0.42-0.96, log-rank p = 0.006, respectively) after adjustment for age, sex and TNM stage. Our data suggest that genetic variation especially in the transmembrane mucin gene MUC4 may play a role in the survival of CRC and further studies are warranted.
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- $a Catalano, Calogerina $u Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany.
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