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Association Analysis between Body Mass Index and Genomic DNA Methylation across 15 Major Cancer Types

Cancer incidence and mortality increase with increasing body mass index (BMI), but BMI-associated epigenetic alterations in cancer remain elusive. We hypothesized that BMI would be associated with DNA methylation alterations in cancers. To test this hypothesis, here, we estimated the associations be...

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Autores principales: Gu, Yinmin, Zhang, Catherine Wei-Hong, Wang, Liang, Zhao, Yuhui, Wang, Hui, Ye, Qinong, Gao, Shan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6036895/
https://www.ncbi.nlm.nih.gov/pubmed/30026852
http://dx.doi.org/10.7150/jca.23535
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author Gu, Yinmin
Zhang, Catherine Wei-Hong
Wang, Liang
Zhao, Yuhui
Wang, Hui
Ye, Qinong
Gao, Shan
author_facet Gu, Yinmin
Zhang, Catherine Wei-Hong
Wang, Liang
Zhao, Yuhui
Wang, Hui
Ye, Qinong
Gao, Shan
author_sort Gu, Yinmin
collection PubMed
description Cancer incidence and mortality increase with increasing body mass index (BMI), but BMI-associated epigenetic alterations in cancer remain elusive. We hypothesized that BMI would be associated with DNA methylation alterations in cancers. To test this hypothesis, here, we estimated the associations between DNA methylation and BMI through two different methods across 15 cancer types, at approximately 485,000 CpG sites and 2415 samples using data from The Cancer Genome Atlas. After comparing the DNA methylation levels in control BMI and high BMI individuals, we found differentially methylated CpG sites (DMSs) in cholangiocarcinoma (CHOL), colon adenocarcinoma (COAD), and uterine corpus endometrial carcinoma (UCEC) (False Discovery Rate < 0.05). The DMSs of COAD or UCEC were enriched in several obesity-induced and cancer-related pathways. Next, when BMI was used as a continuous variable, we identified BMI-associated methylated CpG sites (BMS) (P (Bonferroni) < 0.05) in CHOL (BMS = 1), COAD (BMS = 1), and UCEC (BMS = 4) using multivariable linear regression. In UCEC, three of the BMSs can predict the clinical outcomes and survival of patients with the tumors. Overall, we observed associations between DNA methylation and high BMI in CHOL, COAD, and UCEC. Furthermore, three BMI-associated CpGs were identified as potential biomarkers for UCEC prognosis.
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spelling pubmed-60368952018-07-19 Association Analysis between Body Mass Index and Genomic DNA Methylation across 15 Major Cancer Types Gu, Yinmin Zhang, Catherine Wei-Hong Wang, Liang Zhao, Yuhui Wang, Hui Ye, Qinong Gao, Shan J Cancer Research Paper Cancer incidence and mortality increase with increasing body mass index (BMI), but BMI-associated epigenetic alterations in cancer remain elusive. We hypothesized that BMI would be associated with DNA methylation alterations in cancers. To test this hypothesis, here, we estimated the associations between DNA methylation and BMI through two different methods across 15 cancer types, at approximately 485,000 CpG sites and 2415 samples using data from The Cancer Genome Atlas. After comparing the DNA methylation levels in control BMI and high BMI individuals, we found differentially methylated CpG sites (DMSs) in cholangiocarcinoma (CHOL), colon adenocarcinoma (COAD), and uterine corpus endometrial carcinoma (UCEC) (False Discovery Rate < 0.05). The DMSs of COAD or UCEC were enriched in several obesity-induced and cancer-related pathways. Next, when BMI was used as a continuous variable, we identified BMI-associated methylated CpG sites (BMS) (P (Bonferroni) < 0.05) in CHOL (BMS = 1), COAD (BMS = 1), and UCEC (BMS = 4) using multivariable linear regression. In UCEC, three of the BMSs can predict the clinical outcomes and survival of patients with the tumors. Overall, we observed associations between DNA methylation and high BMI in CHOL, COAD, and UCEC. Furthermore, three BMI-associated CpGs were identified as potential biomarkers for UCEC prognosis. Ivyspring International Publisher 2018-06-22 /pmc/articles/PMC6036895/ /pubmed/30026852 http://dx.doi.org/10.7150/jca.23535 Text en © Ivyspring International Publisher This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Gu, Yinmin
Zhang, Catherine Wei-Hong
Wang, Liang
Zhao, Yuhui
Wang, Hui
Ye, Qinong
Gao, Shan
Association Analysis between Body Mass Index and Genomic DNA Methylation across 15 Major Cancer Types
title Association Analysis between Body Mass Index and Genomic DNA Methylation across 15 Major Cancer Types
title_full Association Analysis between Body Mass Index and Genomic DNA Methylation across 15 Major Cancer Types
title_fullStr Association Analysis between Body Mass Index and Genomic DNA Methylation across 15 Major Cancer Types
title_full_unstemmed Association Analysis between Body Mass Index and Genomic DNA Methylation across 15 Major Cancer Types
title_short Association Analysis between Body Mass Index and Genomic DNA Methylation across 15 Major Cancer Types
title_sort association analysis between body mass index and genomic dna methylation across 15 major cancer types
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6036895/
https://www.ncbi.nlm.nih.gov/pubmed/30026852
http://dx.doi.org/10.7150/jca.23535
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