Identification of polymorphisms in cancer patients that differentially affect survival with age

Doherty, Aoife, Kernogitski, Yelena, Kulminski, Alexander M and de Magalhaes, Joao Pedro ORCID: 0000-0002-6363-2465 (2017) Identification of polymorphisms in cancer patients that differentially affect survival with age. AGING-US, 9 (10). 2114-+.

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Abstract

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 (<i>SIRT3</i>) 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.

Item Type:	Article
Uncontrolled Keywords:	ageing, genetics, geriatric oncology, SNP, longevity, WRN
Depositing User:	Symplectic Admin
Date Deposited:	08 Feb 2018 11:34
Last Modified:	19 Jan 2023 06:42
DOI:	10.18632/aging.101305
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3017704