Please use this identifier to cite or link to this item:
https://ninho.inca.gov.br/jspui/handle/123456789/6943
Title: | Polymorphisms in CYP1B1, CYP3A5, GSTT1, and SULT1A1 Are Associated with Early Age Acute Leukemia |
Authors: | Lopes, Bruno de Almeida Emerenciano, Mariana Gonçalves, Bruno Alves de Aguiar Vieira, Tállita Meciany Farias Rossini, Ana Pombo-de-Oliveira, Maria do Socorro |
Keywords: | Leucemia Mieloide Aguda Leukemia, Myeloid, Acute Células Precursoras de Linfócitos T Precursor Cells, T-Lymphoid Citocromo P-450 CYP2A6 Cytochrome P-450 CYP2A6 Fatores Sexuais Sex Factors Factores Sexuales Polimorfismo de Nucleotídeo Único Polymorphism, Single Nucleotide Polimorfismo de Nucleótido Simple |
Issue Date: | 2015 |
Publisher: | PloS one. |
Abstract: | Based on observational studies, early age leukemia (EAL) was associated with maternal hormone exposure during pregnancy. We studied the association between genetic polymorphisms of estrogen metabolism and EAL. Using data from the Brazilian Collaborative Study Group of Infant Acute Leukemia (2000–2012), 350 cases and 404 age-matched controls and 134 mothers of cases and controls were genotyped to explore polymorphisms in genes of the estrogen metabolism pathway: CYP1B1 (c.1294C>G, rs1056836), CYP3A4 (c.-392A>G, rs2740574), CYP3A5 (c.219-237G>A, rs776746), GSTM1/GSTT1 deletions, and SULT1A1 (c.638G>A, rs9282861; and c.667A>G, rs1801030). Logistic regression was used to calculate the odds ratios (OR) with 95% confidence intervals (CIs), and unconditional logistic regression was used to estimate adjusted odds ratios (aORs) by ethnicity. Because of multiple testing, p values < 0.01 were significant after Bonferroni correction. SULT1A1 (c.638G>A) was associated to infant acute lymphoblastic leukemia and acute myeloid leukemia (AML) risk in males (additive model: aOR = 0.52; 95% CI: 0.29–0.95, p = 0.03; dominant model: aOR = 2.18; 95% CI: 1.17–4.05, p = 0.01, respectively). CYP1B1 polymorphism was associated with a decreased risk of AML either for non-white or female children (additive model: OR = 0.24; 95% CI: 0.08–0.76, p < 0.01; additive model: aOR = 0.27; 95% CI: 0.08–0.89, p = 0.03, respectively). Since polymorphisms of Cytochrome P450 genes presented gender-specific risk associations, we also investigated their expression. CYP1B1 was not expressed in 57.1% of EAL cases, and its expression varied by genotype, gender, and leukemia subtype. Maternal-fetal GSTT1 null genotype was associated with risk of EAL. This study shows that polymorphisms in genes of estrogen metabolism confer genetic susceptibility to EAL, mainly in males, and maternal susceptibility genes modify the risk for developing EAL in newborns |
URI: | http://sr-vmlxaph03:8080/jspui/handle/123456789/6943 |
ISSN: | 1932-6203 |
Appears in Collections: | Artigo de Periódicos da Pesquisa Clínica |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
Polymorphisms in CYP1B1, CYP3A5, GSTT1.pdf | 706.49 kB | Adobe PDF | View/Open |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.