Angela Gutierrez-Camino1, Elixabet Lopez-Lopez1, Idoia Martin-Guerrero1, Maria A Piñan2, Purificacion Garcia-Miguel3, Jose Sanchez-Toledo4, Ana Carbone Bañeres5, Javier Uriz6, Aurora Navajas7, Africa Garcia-Orad1. 1. Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country (UPV/EHU), Leioa, Spain. 2. Department of Hematology and Hemotherapy, University Hospital Cruces, Bilbao, Spain. 3. Service of Pediatric Oncohematology, University Hospital La Paz, Madrid, Spain. 4. Service of Pediatric Oncology and Hematology, University Hospital Vall d' Hebron, VHIR, Barcelona, Spain. 5. Unit of Pediatric Oncohematology, University Hospital Miguel Servet, Zaragoza, Spain. 6. Unit of Pediatric Oncohematology, University Hospital Donostia, San Sebastian, Spain. 7. Unit of Pediatric Hematology/Oncology, University Hospital Cruces, Bilbao, Spain.
Abstract
BACKGROUND: Evidence for an inherited genetic risk for pediatric acute lymphoblastic leukemia has been provided in several studies. Most of them focused on coding regions. However, those regions represent only 1.5% of the entire genome. In acute lymphoblastic leukemia (ALL), it has been suggested that the expression of microRNAs (miRNAs) is dysregulated, which suggests that they may have a role in ALL risk. Changes in miRNA function may occur through single-nucleotide polymorphisms (SNPs). Therefore, the aim of this study was to evaluate whether polymorphisms in pre-miRNAs, and/or miRNA-processing genes, contribute to a predisposition for childhood ALL. METHODS: In this study, we analyzed 118 SNPs in pre-miRNAs and miRNA-processing genes in 213 B-cell ALL patients and 387 controls. RESULTS: We found 11 SNPs significantly associated with ALL susceptibility. These included three SNPs present in miRNA genes (miR-612, miR-499, and miR-449b) and eight SNPs present in six miRNA biogenesis pathway genes (TNRC6B, DROSHA, DGCR8, EIF2C1, CNOT1, and CNOT6). Among the 118 SNPs analyzed, rs12803915 in mir-612 and rs3746444 in mir-499 exhibited a more significant association, with a P value <0.01. CONCLUSION: The results of this study indicate that SNP rs12803915 located in pre-mir-612, and SNP rs3746444 located in pre-mir-499, may represent novel markers of B-cell ALL susceptibility.
BACKGROUND: Evidence for an inherited genetic risk for pediatric acute lymphoblastic leukemia has been provided in several studies. Most of them focused on coding regions. However, those regions represent only 1.5% of the entire genome. In acute lymphoblastic leukemia (ALL), it has been suggested that the expression of microRNAs (miRNAs) is dysregulated, which suggests that they may have a role in ALL risk. Changes in miRNA function may occur through single-nucleotide polymorphisms (SNPs). Therefore, the aim of this study was to evaluate whether polymorphisms in pre-miRNAs, and/or miRNA-processing genes, contribute to a predisposition for childhood ALL. METHODS: In this study, we analyzed 118 SNPs in pre-miRNAs and miRNA-processing genes in 213 B-cell ALL patients and 387 controls. RESULTS: We found 11 SNPs significantly associated with ALL susceptibility. These included three SNPs present in miRNA genes (miR-612, miR-499, and miR-449b) and eight SNPs present in six miRNA biogenesis pathway genes (TNRC6B, DROSHA, DGCR8, EIF2C1, CNOT1, and CNOT6). Among the 118 SNPs analyzed, rs12803915 in mir-612 and rs3746444 in mir-499 exhibited a more significant association, with a P value <0.01. CONCLUSION: The results of this study indicate that SNP rs12803915 located in pre-mir-612, and SNP rs3746444 located in pre-mir-499, may represent novel markers of B-cell ALL susceptibility.
Authors: Tatiane Piedade de Souza; Darlen Cardoso de Carvalho; Alayde Viera Wanderley; Sweny Marinho Fernandes; Juliana Carla Gomes Rodrigues; Amanda Cohen-Paes; Marianne Rodrigues Fernandes; Fernando Augusto Rodrigues Mello Junior; Lucas Favacho Pastana; Lui Wallacy Morikawa Souza Vinagre; Artur Luiz da Costa Silva; Paulo Pimentel de Assumpção; Sidney Santos; André Salim Khayat; Ney Pereira Carneiro Dos Santos Journal: Am J Transl Res Date: 2020-12-15 Impact factor: 4.060