title: Germline variation in the 3'-untranslated region of the POU2AF1 gene is associated with susceptibility to lymphoma.
abstract: Genetic variations in certain genes may alter the susceptibility to lymphoma. We searched electronic databases and selected candidate single-nucleotide polymorphisms (SNPs) located within 3'-untranslated regions (3'-UTRs) that might affect miRNA-binding ability in the 50 most dysregulated genes in lymphoma for further study. We found that rs1042752-located in the 3'-UTR of POU2AF1, which plays a vital role in lymphomagenesis-was significantly associated with lymphoma risk in a case-control study with 793 patients and 939 controls. Compared with individuals with the rs1042752TT genotype, those with the rs1042752CC genotype had a higher risk of lymphoma (OR = 2.14, 95% CI: 1.55-2.95, P < 0.001), even in stratified analysis for non-Hodgkin lymphoma (OR = 4.58, 95% CI: 2.38-8.81, P < 0.001), B-cell lymphoma (OR = 4.89, 95% CI: 2.46-9.73, P < 0.001), T-cell lymphoma (OR = 4.20, 95% CI: 1.76-10.05, P = 0.001), and Hodgkin lymphoma (OR = 3.62, 95% CI: 1.25-10.46, P = 0.018). Similar results were also observed in a recessive genetic model. Database findings suggested that rs1042752 might affect the interaction of POU2AF1 mRNA with hsa-miR-633. Functional assays confirmed that rs1042752C altered the binding site of hsa-miR-633 and increased POU2AF1 expression in Ramos, HuT 102, and Jurkat E6-1 cell lines. These findings demonstrate for the first time that functional polymorphism in the 3'-UTR of POU2AF1 is associated with susceptibility, and that SNP interaction with hsa-miR-633 affects gene expression and increases the risk of lymphoma.
authors.affiliation: Medical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
authors.forename: Kan
authors.identifier: 0000-0002-6495-3690
authors.initials: K
authors.lastname: Zhai
authors.affiliation: State Key Laboratory of Environment Health (Incubation), MOE (Ministry of Education) Key Laboratory of Environment and Health, Ministry of Environmental Protection Key Laboratory of Environment and Health (Wuhan) and School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Chang
authors.affiliation: Department of Oncology, People's Hospital of Zhengzhou University and Henan Provincial People's Hospital, Zhengzhou, China.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Etiology and Carcinogenesis, Chinese Academy of Medical Science and Peking Union Medical College, Cancer Institute and Hospital, Beijing, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Etiology and Carcinogenesis, Chinese Academy of Medical Science and Peking Union Medical College, Cancer Institute and Hospital, Beijing, China.
authors.forename: Dongxin
authors.initials: D
authors.lastname: Lin
mesh_terms: D020413:3' Untranslated Regions; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D008223:Lymphoma / Q000235:genetics* / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; C577857:MIRN633 microRNA, human; D035683:MicroRNAs; C091546:POU2AF1 protein, human; D012333:RNA, Messenger; D015534:Trans-Activators
keywords: 3'-untranslated region; lymphoma; microRNA; single nucleotide polymorphism; susceptibility