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RAS mutations in early age leukaemia modulated by NQO1 rs1800566 (C609T) are associated with second-hand smoking exposures

BACKGROUND: Deregulation of the MAPK genes signalling caused by somatic mutations have been implied in leukaemia pathogenesis, including RAS mutation (RAS(mut)) in acute myeloid leukaemia (AML), which has been associated with intra-uterine chemical exposures. A case-case study was conducted in order...

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Autores principales: Andrade, Francianne Gomes, Furtado-Silva, Juliana Montibeller, Gonçalves, Bruno Alves de Aguiar, Thuler, Luiz Claudio Santos, Barbosa, Thayana Conceição, Emerenciano, Mariana, Siqueira, André, Pombo-de-Oliveira, Maria S
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946262/
https://www.ncbi.nlm.nih.gov/pubmed/24571676
http://dx.doi.org/10.1186/1471-2407-14-133
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author Andrade, Francianne Gomes
Furtado-Silva, Juliana Montibeller
Gonçalves, Bruno Alves de Aguiar
Thuler, Luiz Claudio Santos
Barbosa, Thayana Conceição
Emerenciano, Mariana
Siqueira, André
Pombo-de-Oliveira, Maria S
author_facet Andrade, Francianne Gomes
Furtado-Silva, Juliana Montibeller
Gonçalves, Bruno Alves de Aguiar
Thuler, Luiz Claudio Santos
Barbosa, Thayana Conceição
Emerenciano, Mariana
Siqueira, André
Pombo-de-Oliveira, Maria S
author_sort Andrade, Francianne Gomes
collection PubMed
description BACKGROUND: Deregulation of the MAPK genes signalling caused by somatic mutations have been implied in leukaemia pathogenesis, including RAS mutation (RAS(mut)) in acute myeloid leukaemia (AML), which has been associated with intra-uterine chemical exposures. A case-case study was conducted in order to explore maternal and child exposures to tobacco smoking associations with early age leukaemia (EAL). METHODS: Covariables of reference were MLL rearrangements (MLL-r), RAS(mut) and NQO1 rs1800566 (C609T). Samples from 150 acute lymphoblastic leukaemia (ALL) and 85 AML were included. Maternal exposures were assessed using a structured questionnaire with demographic, personal habits and residence history information. Restriction fragment length polymorphism and denaturing high performance liquid chromatography were used to screen FLT3, KRAS, and NRAS mutations; direct sequencing was performed to validate the results. NQO1 polymorphism was detected by real-time allelic discrimination technique. RESULTS: Overall, RAS(mut) were detected in 28.7% of EAL cases; BRAF(mut) was found only in one AML patient. Higher rate of KRAS(mut) was found in ALL (30.3%) compared to AML (20.8%) with MLL-r; RAS(mut) showed an association with second-hand tobacco smoking exposures (OR, 3.06, 95% CI, 1.03-9.07). A considerable increased risk for EAL with the combination of RAS(mut) and NQO1 609CT (OR, 4.24, 95% CI, 1.24-14.50) was observed. CONCLUSIONS: Our data demonstrated the increased risk association between maternal smoking and EAL with MLL-r. Additionally, suggests that children second-hand tobacco exposures are associated with increased risk of EAL with RAS(mut) modulated by NQO1 rs1800566 (C609T).
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spelling pubmed-39462622014-03-09 RAS mutations in early age leukaemia modulated by NQO1 rs1800566 (C609T) are associated with second-hand smoking exposures Andrade, Francianne Gomes Furtado-Silva, Juliana Montibeller Gonçalves, Bruno Alves de Aguiar Thuler, Luiz Claudio Santos Barbosa, Thayana Conceição Emerenciano, Mariana Siqueira, André Pombo-de-Oliveira, Maria S BMC Cancer Research Article BACKGROUND: Deregulation of the MAPK genes signalling caused by somatic mutations have been implied in leukaemia pathogenesis, including RAS mutation (RAS(mut)) in acute myeloid leukaemia (AML), which has been associated with intra-uterine chemical exposures. A case-case study was conducted in order to explore maternal and child exposures to tobacco smoking associations with early age leukaemia (EAL). METHODS: Covariables of reference were MLL rearrangements (MLL-r), RAS(mut) and NQO1 rs1800566 (C609T). Samples from 150 acute lymphoblastic leukaemia (ALL) and 85 AML were included. Maternal exposures were assessed using a structured questionnaire with demographic, personal habits and residence history information. Restriction fragment length polymorphism and denaturing high performance liquid chromatography were used to screen FLT3, KRAS, and NRAS mutations; direct sequencing was performed to validate the results. NQO1 polymorphism was detected by real-time allelic discrimination technique. RESULTS: Overall, RAS(mut) were detected in 28.7% of EAL cases; BRAF(mut) was found only in one AML patient. Higher rate of KRAS(mut) was found in ALL (30.3%) compared to AML (20.8%) with MLL-r; RAS(mut) showed an association with second-hand tobacco smoking exposures (OR, 3.06, 95% CI, 1.03-9.07). A considerable increased risk for EAL with the combination of RAS(mut) and NQO1 609CT (OR, 4.24, 95% CI, 1.24-14.50) was observed. CONCLUSIONS: Our data demonstrated the increased risk association between maternal smoking and EAL with MLL-r. Additionally, suggests that children second-hand tobacco exposures are associated with increased risk of EAL with RAS(mut) modulated by NQO1 rs1800566 (C609T). BioMed Central 2014-02-26 /pmc/articles/PMC3946262/ /pubmed/24571676 http://dx.doi.org/10.1186/1471-2407-14-133 Text en Copyright © 2014 Andrade et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.
spellingShingle Research Article
Andrade, Francianne Gomes
Furtado-Silva, Juliana Montibeller
Gonçalves, Bruno Alves de Aguiar
Thuler, Luiz Claudio Santos
Barbosa, Thayana Conceição
Emerenciano, Mariana
Siqueira, André
Pombo-de-Oliveira, Maria S
RAS mutations in early age leukaemia modulated by NQO1 rs1800566 (C609T) are associated with second-hand smoking exposures
title RAS mutations in early age leukaemia modulated by NQO1 rs1800566 (C609T) are associated with second-hand smoking exposures
title_full RAS mutations in early age leukaemia modulated by NQO1 rs1800566 (C609T) are associated with second-hand smoking exposures
title_fullStr RAS mutations in early age leukaemia modulated by NQO1 rs1800566 (C609T) are associated with second-hand smoking exposures
title_full_unstemmed RAS mutations in early age leukaemia modulated by NQO1 rs1800566 (C609T) are associated with second-hand smoking exposures
title_short RAS mutations in early age leukaemia modulated by NQO1 rs1800566 (C609T) are associated with second-hand smoking exposures
title_sort ras mutations in early age leukaemia modulated by nqo1 rs1800566 (c609t) are associated with second-hand smoking exposures
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946262/
https://www.ncbi.nlm.nih.gov/pubmed/24571676
http://dx.doi.org/10.1186/1471-2407-14-133
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