机构:[1]Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany[2]Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China四川省人民医院四川省肿瘤医院[3]Department of Multiple Myeloma, Internal Medicine V: Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Heidelberg, Germany[4]Italian Institute for Genomic Medicine (IIGM), Turin, Italy[5]Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic[6]Department of Medical Genetics, Third Faculty of Medicine, Charles University, Prague, Czech Republic[7]Institute of Biology and Medical Genetics, 1stMedical Faculty, Charles University, Prague, Czech Republic[8]Biomedical Centre, Faculty of Medicine in Pilsen, Charles University in Prague, Pilsen, Czech Republic[9]Department of Oncology, Thomayer Hospital, Prague, Czech Republic[10]Center of Primary Health Care Research, Clinical Research Center, Lund University, Malmo¨ , Sweden
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 (r(2)>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, logrank 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.
基金:
Ministry
of Health of the Czech Republic (AZV 15-27580A)
to PV and by Grantova′ Agentura Česke′ Republiky
(GACR 17-16857S) to BP.
第一作者机构:[1]Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany[2]Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
通讯作者:
通讯机构:[1]Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany[2]Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China[10]Center of Primary Health Care Research, Clinical Research Center, Lund University, Malmo¨ , Sweden
推荐引用方式(GB/T 7714):
Lu Shun,Catalano Calogerina,Huhn Stefanie,et al.Single nucleotide polymorphisms within MUC4 are associated with colorectal cancer survival[J].PLOS ONE.2019,14(5):doi:10.1371/journal.pone.0216666.
APA:
Lu, Shun,Catalano, Calogerina,Huhn, Stefanie,Pardini, Barbara,Partu, Linda...&Foersti, Asta.(2019).Single nucleotide polymorphisms within MUC4 are associated with colorectal cancer survival.PLOS ONE,14,(5)
MLA:
Lu, Shun,et al."Single nucleotide polymorphisms within MUC4 are associated with colorectal cancer survival".PLOS ONE 14..5(2019)