title: CXCL12 and TP53 genetic polymorphisms as markers of susceptibility in a Brazilian children population with acute lymphoblastic leukemia (ALL).
abstract: Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. Genetic polymorphisms in the 3'UTR region of the CXCL12 (rs1801157) and TP53 codon 72 (rs1042522) genes may contribute to susceptibility to childhood ALL because they affect some important processes, such as metastasis regulation and tumor suppression. Thus the objective of the present study was to detect the frequency of two genetic polymorphisms in ALL patients and controls and to add information their impact on genetic susceptibility and prognosis. The CXCL12 and TP53 polymorphisms were tested in 54 ALL child patients and in 58 controls by restriction fragment length polymerase chain reaction and allelic specific chain reaction techniques, respectively. The frequencies of both allelic variants were higher in ALL patients than in the controls and indicated a positive association: OR = 2.44; 95 % CI 1.05-5.64 for CXCL12 and OR = 2.20; 95 % CI 1.03-4.70 for TP53. Furthermore, when the two genetic variants were analyzed together, they increased significantly more than fivefold the risk of this neoplasia development (OR = 5.24; 95 % CI 1.39-19.75), indicating their potential as susceptibility markers for ALL disease and the relevance of the allelic variant combination to increased risk of developing malignant tumors. Future studies may indicate a larger panel of genes involved in susceptibility of childhood ALL and other hematological neoplasias.
authors: Laboratory of Study and Applications of DNA Polymorphisms, Department of Pathological Science, Biological Science Center, State University of Londrina, Campus Universitário-Rod. Celso Garcia Cid (PR 445) Km 380, Londrina, PR, CEP 86051-970, Brazil.
authors: Aparecida
authors: A
authors: de Lourdes Perim
authors: Roberta Losi
authors: RL
authors: Guembarovski
authors: Julie Massayo Maeda
authors: JM
authors: Oda
authors: Leandra Fiori
authors: LF
authors: Lopes
authors: Carolina Batista
authors: CB
authors: Ariza
authors: Marla Karine
authors: MK
authors: Amarante
authors: Maria Helena Pelegrinelli
authors: MH
authors: Fungaro
authors: Karen Brajão
authors: KB
authors: de Oliveira
authors: Maria Angelica Ehara
authors: MA
authors: Watanabe
mesh_terms: D000293:Adolescent; D014408:Biomarkers, Tumor; D001938:Brazil; D016022:Case-Control Studies; D054377:Chemokine CXCL12 / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D054377:Chemokine CXCL12; D016159:Tumor Suppressor Protein p53
references: Nat Rev Cancer. 2010 May;10(5):353-61
references: 20414203
references: J Leukoc Biol. 2011 Jan;89(1):31-9
references: 20628066
references: J Clin Lab Anal. 2009;23(6):387-93
references: 19927352
references: Hematology Am Soc Hematol Educ Program. 2000;:285-302
references: 11701547
references: Transfus Apher Sci. 2011 Apr;44(2):183-9
references: 21354375
references: Med Oncol. 2011 Sep;28(3):709-15
references: 20443084
references: Cancer Res. 2006 Nov 15;66(22):10671-6
references: 17108103
references: Blood. 2004 Nov 1;104(9):2690-6
references: 15251979
references: Lancet. 2008 Mar 22;371(9617):1030-43
references: 18358930
references: Blood Cells Mol Dis. 2004 Jul-Aug;33(1):90-3
references: 15223017
references: J Biosci. 2011 Dec;36(5):823-31
references: 22116280
references: Cold Spring Harb Perspect Biol. 2010 Jan;2(1):a001008
references: 20182602
references: Mutat Res. 2005 May;589(3):192-207
references: 15878142
references: Nature. 2001 Mar 1;410(6824):50-6
references: 11242036
references: Cancer Genet Cytogenet. 2009 Nov;195(1):31-6
references: 19837266
references: Cytokine. 2011 Aug;55(2):260-5
references: 21592819
references: J Biosci. 2012 Mar;37(1):33-9
references: 22357201
references: Environ Health Perspect. 2007 Jan;115(1):138-45
references: 17366834
references: Nat Rev Mol Cell Biol. 2007 Apr;8(4):275-83
references: 17380161
references: Leukemia. 2009 Dec;23(12):2233-41
references: 19727127
references: Mol Cell Biol. 1987 Feb;7(2):961-3
references: 3547088
references: Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi. 1995 Sep-Oct;36(5):322-7
references: 8607355
references: J Neurooncol. 2012 Oct;110(1):49-57
references: 22886512
references: Int J Mol Med. 2009 Mar;23(3):429-35
references: 19212663
references: Hepatogastroenterology. 2011 Nov-Dec;58(112):1926-9
references: 22234063
references: Nat Rev Cancer. 2002 Aug;2(8):594-604
references: 12154352
references: J Clin Lab Anal. 2007;21(1):49-54
references: 17245764