Genomic determinants of long-term cardiometabolic complications in childhood acute lymphoblastic leukemia survivors
Abstract Background While cure rates for childhood acute lymphoblastic leukemia (cALL) now exceed 80%, over 60% of survivors will face treatment-related long-term sequelae, including cardiometabolic complications such as obesity, insulin resistance, dyslipidemia and hypertension. Although genetic su...
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doaj-b907a1bfe5634b268f59734cf81383222020-11-25T01:53:23ZengBMCBMC Cancer1471-24072017-11-0117111410.1186/s12885-017-3722-6Genomic determinants of long-term cardiometabolic complications in childhood acute lymphoblastic leukemia survivorsJade England0Simon Drouin1Patrick Beaulieu2Pascal St-Onge3Maja Krajinovic4Caroline Laverdière5Emile Levy6Valérie Marcil7Daniel Sinnett8Research Centre, Sainte-Justine University Health CenterResearch Centre, Sainte-Justine University Health CenterResearch Centre, Sainte-Justine University Health CenterResearch Centre, Sainte-Justine University Health CenterResearch Centre, Sainte-Justine University Health CenterResearch Centre, Sainte-Justine University Health CenterResearch Centre, Sainte-Justine University Health CenterResearch Centre, Sainte-Justine University Health CenterResearch Centre, Sainte-Justine University Health CenterAbstract Background While cure rates for childhood acute lymphoblastic leukemia (cALL) now exceed 80%, over 60% of survivors will face treatment-related long-term sequelae, including cardiometabolic complications such as obesity, insulin resistance, dyslipidemia and hypertension. Although genetic susceptibility contributes to the development of these problems, there are very few studies that have so far addressed this issue in a cALL survivorship context. Methods In this study, we aimed at evaluating the associations between common and rare genetic variants and long-term cardiometabolic complications in survivors of cALL. We examined the cardiometabolic profile and performed whole-exome sequencing in 209 cALL survivors from the PETALE cohort. Variants associated with cardiometabolic outcomes were identified using PLINK (common) or SKAT (common and rare) and a logistic regression was used to evaluate their impact in multivariate models. Results Our results showed that rare and common variants in the BAD and FCRL3 genes were associated (p<0.05) with an extreme cardiometabolic phenotype (3 or more cardiometabolic risk factors). Common variants in OGFOD3 and APOB as well as rare and common BAD variants were significantly (p<0.05) associated with dyslipidemia. Common BAD and SERPINA6 variants were associated (p<0.05) with obesity and insulin resistance, respectively. Conclusions In summary, we identified genetic susceptibility loci as contributing factors to the development of late treatment-related cardiometabolic complications in cALL survivors. These biomarkers could be used as early detection strategies to identify susceptible individuals and implement appropriate measures and follow-up to prevent the development of risk factors in this high-risk population.http://link.springer.com/article/10.1186/s12885-017-3722-6Acute lymphoblastic leukemiacancer survivorsgenetic determinantscardiometabolic complicationsgenetic association studyextreme phenotype |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jade England Simon Drouin Patrick Beaulieu Pascal St-Onge Maja Krajinovic Caroline Laverdière Emile Levy Valérie Marcil Daniel Sinnett |
spellingShingle |
Jade England Simon Drouin Patrick Beaulieu Pascal St-Onge Maja Krajinovic Caroline Laverdière Emile Levy Valérie Marcil Daniel Sinnett Genomic determinants of long-term cardiometabolic complications in childhood acute lymphoblastic leukemia survivors BMC Cancer Acute lymphoblastic leukemia cancer survivors genetic determinants cardiometabolic complications genetic association study extreme phenotype |
author_facet |
Jade England Simon Drouin Patrick Beaulieu Pascal St-Onge Maja Krajinovic Caroline Laverdière Emile Levy Valérie Marcil Daniel Sinnett |
author_sort |
Jade England |
title |
Genomic determinants of long-term cardiometabolic complications in childhood acute lymphoblastic leukemia survivors |
title_short |
Genomic determinants of long-term cardiometabolic complications in childhood acute lymphoblastic leukemia survivors |
title_full |
Genomic determinants of long-term cardiometabolic complications in childhood acute lymphoblastic leukemia survivors |
title_fullStr |
Genomic determinants of long-term cardiometabolic complications in childhood acute lymphoblastic leukemia survivors |
title_full_unstemmed |
Genomic determinants of long-term cardiometabolic complications in childhood acute lymphoblastic leukemia survivors |
title_sort |
genomic determinants of long-term cardiometabolic complications in childhood acute lymphoblastic leukemia survivors |
publisher |
BMC |
series |
BMC Cancer |
issn |
1471-2407 |
publishDate |
2017-11-01 |
description |
Abstract Background While cure rates for childhood acute lymphoblastic leukemia (cALL) now exceed 80%, over 60% of survivors will face treatment-related long-term sequelae, including cardiometabolic complications such as obesity, insulin resistance, dyslipidemia and hypertension. Although genetic susceptibility contributes to the development of these problems, there are very few studies that have so far addressed this issue in a cALL survivorship context. Methods In this study, we aimed at evaluating the associations between common and rare genetic variants and long-term cardiometabolic complications in survivors of cALL. We examined the cardiometabolic profile and performed whole-exome sequencing in 209 cALL survivors from the PETALE cohort. Variants associated with cardiometabolic outcomes were identified using PLINK (common) or SKAT (common and rare) and a logistic regression was used to evaluate their impact in multivariate models. Results Our results showed that rare and common variants in the BAD and FCRL3 genes were associated (p<0.05) with an extreme cardiometabolic phenotype (3 or more cardiometabolic risk factors). Common variants in OGFOD3 and APOB as well as rare and common BAD variants were significantly (p<0.05) associated with dyslipidemia. Common BAD and SERPINA6 variants were associated (p<0.05) with obesity and insulin resistance, respectively. Conclusions In summary, we identified genetic susceptibility loci as contributing factors to the development of late treatment-related cardiometabolic complications in cALL survivors. These biomarkers could be used as early detection strategies to identify susceptible individuals and implement appropriate measures and follow-up to prevent the development of risk factors in this high-risk population. |
topic |
Acute lymphoblastic leukemia cancer survivors genetic determinants cardiometabolic complications genetic association study extreme phenotype |
url |
http://link.springer.com/article/10.1186/s12885-017-3722-6 |
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