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Identification of polymorphisms in cancer patients that differentially affect survival with age
The World Health Organization predicts that the proportion of the world's population over 60 will almost double from 12% to 22% between 2015 and 2050. Ageing is the biggest risk factor for cancer, which is a leading cause of deaths worldwide. Unfortunately, research describing how genetic varia...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5680559/ https://www.ncbi.nlm.nih.gov/pubmed/29064820 http://dx.doi.org/10.18632/aging.101305 |
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author | Doherty, Aoife Kernogitski, Yelena Kulminski, Alexander M. de Magalhães, João Pedro |
author_facet | Doherty, Aoife Kernogitski, Yelena Kulminski, Alexander M. de Magalhães, João Pedro |
author_sort | Doherty, Aoife |
collection | PubMed |
description | The World Health Organization predicts that the proportion of the world's population over 60 will almost double from 12% to 22% between 2015 and 2050. Ageing is the biggest risk factor for cancer, which is a leading cause of deaths worldwide. Unfortunately, research describing how genetic variants affect cancer progression commonly neglects to account for the ageing process. Herein is the first systematic analysis that combines a large longitudinal data set with a targeted candidate gene approach to examine the effect of genetic variation on survival as a function of age in cancer patients. Survival was significantly decreased in individuals with heterozygote or rare homozygote (i.e. variant) genotypes compared to those with a common homozygote genotype (i.e. wild type) for two single nucleotide polymorphisms (rs11574358 and rs4147918), one gene (SIRT3) and one pathway (FoxO signalling) in an age-dependent manner. All identified genes and pathways have previously been associated with ageing and cancer. These observations demonstrate that there are ageing-related genetic elements that differentially affect mortality in cancer patients in an age-dependent manner. Understanding the genetic determinants affecting prognosis differently with age will be invaluable to develop age-specific prognostic biomarkers and personalized therapies that may improve clinical outcomes for older individuals. |
format | Online Article Text |
id | pubmed-5680559 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-56805592017-11-18 Identification of polymorphisms in cancer patients that differentially affect survival with age Doherty, Aoife Kernogitski, Yelena Kulminski, Alexander M. de Magalhães, João Pedro Aging (Albany NY) Research Paper The World Health Organization predicts that the proportion of the world's population over 60 will almost double from 12% to 22% between 2015 and 2050. Ageing is the biggest risk factor for cancer, which is a leading cause of deaths worldwide. Unfortunately, research describing how genetic variants affect cancer progression commonly neglects to account for the ageing process. Herein is the first systematic analysis that combines a large longitudinal data set with a targeted candidate gene approach to examine the effect of genetic variation on survival as a function of age in cancer patients. Survival was significantly decreased in individuals with heterozygote or rare homozygote (i.e. variant) genotypes compared to those with a common homozygote genotype (i.e. wild type) for two single nucleotide polymorphisms (rs11574358 and rs4147918), one gene (SIRT3) and one pathway (FoxO signalling) in an age-dependent manner. All identified genes and pathways have previously been associated with ageing and cancer. These observations demonstrate that there are ageing-related genetic elements that differentially affect mortality in cancer patients in an age-dependent manner. Understanding the genetic determinants affecting prognosis differently with age will be invaluable to develop age-specific prognostic biomarkers and personalized therapies that may improve clinical outcomes for older individuals. Impact Journals LLC 2017-10-20 /pmc/articles/PMC5680559/ /pubmed/29064820 http://dx.doi.org/10.18632/aging.101305 Text en Copyright: © 2017 Doherty et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Research Paper Doherty, Aoife Kernogitski, Yelena Kulminski, Alexander M. de Magalhães, João Pedro Identification of polymorphisms in cancer patients that differentially affect survival with age |
title | Identification of polymorphisms in cancer patients that differentially affect survival with age |
title_full | Identification of polymorphisms in cancer patients that differentially affect survival with age |
title_fullStr | Identification of polymorphisms in cancer patients that differentially affect survival with age |
title_full_unstemmed | Identification of polymorphisms in cancer patients that differentially affect survival with age |
title_short | Identification of polymorphisms in cancer patients that differentially affect survival with age |
title_sort | identification of polymorphisms in cancer patients that differentially affect survival with age |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5680559/ https://www.ncbi.nlm.nih.gov/pubmed/29064820 http://dx.doi.org/10.18632/aging.101305 |
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