title: Five functional polymorphisms of B7/CD28 co-signaling molecules alter susceptibility to colorectal cancer.
abstract: Polymorphisms within the 3'-untranslated region (3'-UTR) of genes have been proved to contribute to the risk of cancers. Here, we determined 16 putatively functional polymorphisms in the 3'-UTR of 11 B7/CD28 genes in 382 colorectal cancer patients and 714 healthy controls. Statistical analysis revealed that ICOS rs4404254-C-allele carriers (p=0.0014), rs1559931-A-allele carriers (p=0.0027), and rs4675379-C-allele carriers (p=0.026) were significantly fewer in patients than those in controls. B7-H4-rs13505-GG homozygotes were more prevalent in patients (p=0.03). CD80-rs7628626-GT was apparently less in the patients with lymph node metastasis (p=0.004) or in advanced stage (p=0.037). Furthermore, we found that these polymorphisms impacted the regulatory role of miR-21-3p, miR-186-5p, miR-323b-5p, miR-1207-5p, miR-1279, miR-2117, and miR-3692-3p in the expression of the B7/CD28 molecules. Our findings suggest that rs7628626, rs13505, rs4404254, rs1559931, and rs4675379, through disrupting the regulatory role of miRNAs in the expression of B7/CD28 molecules, contribute to the occurrence and progress of colorectal cancer.
authors.affiliation: Center of Drug Metabolism and Pharmacokinetics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China; Department of Oncology, The Fourth Affiliated Hospital of Soochow University, Wuxi 214062, China.
authors.forename: Dongjuan
authors.initials: D
authors.lastname: Wu
authors.affiliation: Center of Drug Metabolism and Pharmacokinetics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Tang
authors.affiliation: Department of Oncology, The Fourth Affiliated Hospital of Soochow University, Wuxi 214062, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Qi
authors.affiliation: Center of Drug Metabolism and Pharmacokinetics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
authors.forename: Xinru
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Clinical Laboratory, The Fourth Affiliated Hospital of Soochow University, Wuxi 214062, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Oncology, The Fourth Affiliated Hospital of Soochow University, Wuxi 214062, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
authors.forename: Cuiping
authors.initials: C
authors.lastname: Liu
authors.affiliation: Center of Drug Metabolism and Pharmacokinetics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China. Electronic address: wangweipeng@suda.edu.cn.
authors.forename: Weipeng
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Oncology, The Fourth Affiliated Hospital of Soochow University, Wuxi 214062, China. Electronic address: huadong@csco.org.cn.
authors.forename: Dong
authors.initials: D
authors.lastname: Hua
authors.affiliation: Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
authors.forename: Xueguang
authors.initials: X
authors.lastname: Zhang
mesh_terms: D020413:3' Untranslated Regions; D000230:Adenocarcinoma / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D000483:Alleles; D018122:B7-1 Antigen / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D018106:CD28 Antigens / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000276:immunology; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic; D015398:Signal Transduction
chemical_list: D020413:3' Untranslated Regions; D018122:B7-1 Antigen; D018106:CD28 Antigens; D035683:MicroRNAs
keywords: Co-signaling molecules; Colorectal cancer; Single nucleotide polymorphism; microRNA