Cargando…

Association of FOXO3 Blood DNA Methylation with Cancer Risk, Cancer Survival, and Mortality

Genetic variants in FOXO3 are associated with longevity. Here, we assessed whether blood DNA methylation at FOXO3 was associated with cancer risk, survival, and mortality. We used data from eight prospective case–control studies of breast (n = 409 cases), colorectal (n = 835), gastric (n = 170), kid...

Descripción completa

Detalles Bibliográficos
Autores principales: Yu, Chenglong, Hodge, Allison M., Wong, Ee Ming, Joo, Jihoon Eric, Makalic, Enes, Schmidt, Daniel, Buchanan, Daniel D., Hopper, John L., Giles, Graham G., Southey, Melissa C., Dugué, Pierre-Antoine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8699522/
https://www.ncbi.nlm.nih.gov/pubmed/34943892
http://dx.doi.org/10.3390/cells10123384
_version_ 1784620533629845504
author Yu, Chenglong
Hodge, Allison M.
Wong, Ee Ming
Joo, Jihoon Eric
Makalic, Enes
Schmidt, Daniel
Buchanan, Daniel D.
Hopper, John L.
Giles, Graham G.
Southey, Melissa C.
Dugué, Pierre-Antoine
author_facet Yu, Chenglong
Hodge, Allison M.
Wong, Ee Ming
Joo, Jihoon Eric
Makalic, Enes
Schmidt, Daniel
Buchanan, Daniel D.
Hopper, John L.
Giles, Graham G.
Southey, Melissa C.
Dugué, Pierre-Antoine
author_sort Yu, Chenglong
collection PubMed
description Genetic variants in FOXO3 are associated with longevity. Here, we assessed whether blood DNA methylation at FOXO3 was associated with cancer risk, survival, and mortality. We used data from eight prospective case–control studies of breast (n = 409 cases), colorectal (n = 835), gastric (n = 170), kidney (n = 143), lung (n = 332), prostate (n = 869), and urothelial (n = 428) cancer and B-cell lymphoma (n = 438). Case–control pairs were matched on age, sex, country of birth, and smoking (lung cancer study). Conditional logistic regression was used to assess associations between cancer risk and methylation at 45 CpGs of FOXO3 included on the HumanMethylation450 assay. Mixed-effects Cox models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations with cancer survival (total n = 2286 deaths). Additionally, using data from 1088 older participants, we assessed associations of FOXO3 methylation with overall and cause-specific mortality (n = 354 deaths). Methylation at a CpG in the first exon region of FOXO3 (6:108882981) was associated with gastric cancer survival (HR = 2.39, 95% CI: 1.60–3.56, p = 1.9 × 10(−5)). Methylation at three CpGs in TSS1500 and gene body was associated with lung cancer survival (p < 6.1 × 10(−5)). We found no evidence of associations of FOXO3 methylation with cancer risk and mortality. Our findings may contribute to understanding the implication of FOXO3 in longevity.
format Online
Article
Text
id pubmed-8699522
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-86995222021-12-24 Association of FOXO3 Blood DNA Methylation with Cancer Risk, Cancer Survival, and Mortality Yu, Chenglong Hodge, Allison M. Wong, Ee Ming Joo, Jihoon Eric Makalic, Enes Schmidt, Daniel Buchanan, Daniel D. Hopper, John L. Giles, Graham G. Southey, Melissa C. Dugué, Pierre-Antoine Cells Article Genetic variants in FOXO3 are associated with longevity. Here, we assessed whether blood DNA methylation at FOXO3 was associated with cancer risk, survival, and mortality. We used data from eight prospective case–control studies of breast (n = 409 cases), colorectal (n = 835), gastric (n = 170), kidney (n = 143), lung (n = 332), prostate (n = 869), and urothelial (n = 428) cancer and B-cell lymphoma (n = 438). Case–control pairs were matched on age, sex, country of birth, and smoking (lung cancer study). Conditional logistic regression was used to assess associations between cancer risk and methylation at 45 CpGs of FOXO3 included on the HumanMethylation450 assay. Mixed-effects Cox models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations with cancer survival (total n = 2286 deaths). Additionally, using data from 1088 older participants, we assessed associations of FOXO3 methylation with overall and cause-specific mortality (n = 354 deaths). Methylation at a CpG in the first exon region of FOXO3 (6:108882981) was associated with gastric cancer survival (HR = 2.39, 95% CI: 1.60–3.56, p = 1.9 × 10(−5)). Methylation at three CpGs in TSS1500 and gene body was associated with lung cancer survival (p < 6.1 × 10(−5)). We found no evidence of associations of FOXO3 methylation with cancer risk and mortality. Our findings may contribute to understanding the implication of FOXO3 in longevity. MDPI 2021-12-01 /pmc/articles/PMC8699522/ /pubmed/34943892 http://dx.doi.org/10.3390/cells10123384 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yu, Chenglong
Hodge, Allison M.
Wong, Ee Ming
Joo, Jihoon Eric
Makalic, Enes
Schmidt, Daniel
Buchanan, Daniel D.
Hopper, John L.
Giles, Graham G.
Southey, Melissa C.
Dugué, Pierre-Antoine
Association of FOXO3 Blood DNA Methylation with Cancer Risk, Cancer Survival, and Mortality
title Association of FOXO3 Blood DNA Methylation with Cancer Risk, Cancer Survival, and Mortality
title_full Association of FOXO3 Blood DNA Methylation with Cancer Risk, Cancer Survival, and Mortality
title_fullStr Association of FOXO3 Blood DNA Methylation with Cancer Risk, Cancer Survival, and Mortality
title_full_unstemmed Association of FOXO3 Blood DNA Methylation with Cancer Risk, Cancer Survival, and Mortality
title_short Association of FOXO3 Blood DNA Methylation with Cancer Risk, Cancer Survival, and Mortality
title_sort association of foxo3 blood dna methylation with cancer risk, cancer survival, and mortality
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8699522/
https://www.ncbi.nlm.nih.gov/pubmed/34943892
http://dx.doi.org/10.3390/cells10123384
work_keys_str_mv AT yuchenglong associationoffoxo3blooddnamethylationwithcancerriskcancersurvivalandmortality
AT hodgeallisonm associationoffoxo3blooddnamethylationwithcancerriskcancersurvivalandmortality
AT wongeeming associationoffoxo3blooddnamethylationwithcancerriskcancersurvivalandmortality
AT joojihooneric associationoffoxo3blooddnamethylationwithcancerriskcancersurvivalandmortality
AT makalicenes associationoffoxo3blooddnamethylationwithcancerriskcancersurvivalandmortality
AT schmidtdaniel associationoffoxo3blooddnamethylationwithcancerriskcancersurvivalandmortality
AT buchanandanield associationoffoxo3blooddnamethylationwithcancerriskcancersurvivalandmortality
AT hopperjohnl associationoffoxo3blooddnamethylationwithcancerriskcancersurvivalandmortality
AT gilesgrahamg associationoffoxo3blooddnamethylationwithcancerriskcancersurvivalandmortality
AT southeymelissac associationoffoxo3blooddnamethylationwithcancerriskcancersurvivalandmortality
AT duguepierreantoine associationoffoxo3blooddnamethylationwithcancerriskcancersurvivalandmortality