Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Doherty, Aoife, Kernogitski, Yelena, Kulminski, Alexander M., de Magalhães, João Pedro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
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
_version_ 1783277785930792960
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
work_keys_str_mv AT dohertyaoife identificationofpolymorphismsincancerpatientsthatdifferentiallyaffectsurvivalwithage
AT kernogitskiyelena identificationofpolymorphismsincancerpatientsthatdifferentiallyaffectsurvivalwithage
AT kulminskialexanderm identificationofpolymorphismsincancerpatientsthatdifferentiallyaffectsurvivalwithage
AT demagalhaesjoaopedro identificationofpolymorphismsincancerpatientsthatdifferentiallyaffectsurvivalwithage