Identification of Polymorphisms in Cancer Patients That Differentially Affect Survival With Age

Aging (Albany NY). 2017 Oct 20;9(10):2117-2136. doi: 10.18632/aging.101305.

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 (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.

Keywords: SNP; WRN; ageing; genetics; geriatric oncology; longevity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aging / genetics
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasms / genetics*
  • Neoplasms / mortality*
  • Polymorphism, Single Nucleotide / genetics*
  • Prognosis
  • Proportional Hazards Models