Common genetic variation associated with increased susceptibility to prostate cancer does not increase risk of radiotherapy toxicity.

Mahbubl Ahmed, Leila Dorling, Sarah Kerns, Laura Fachal, Rebecca Elliott, Matt Partliament, Barry S Rosenstein, Ana Vega, Antonio Gómez-Caamaño, Gill Barnett, David P Dearnaley, Emma Hall, Matt Sydes, Neil Burnet, Paul D P Pharoah, Ros Eeles, Catharine M L West

Research output: Contribution to journalArticlepeer-review


BACKGROUND: Numerous germline single-nucleotide polymorphisms increase susceptibility to prostate cancer, some lying near genes involved in cellular radiation response. This study investigated whether prostate cancer patients with a high genetic risk have increased toxicity following radiotherapy.

METHODS: The study included 1560 prostate cancer patients from four radiotherapy cohorts: RAPPER (n=533), RADIOGEN (n=597), GenePARE (n=290) and CCI (n=150). Data from genome-wide association studies were imputed with the 1000 Genomes reference panel. Individuals were genetically similar with a European ancestry based on principal component analysis. Genetic risks were quantified using polygenic risk scores. Regression models tested associations between risk scores and 2-year toxicity (overall, urinary frequency, decreased stream, rectal bleeding). Results were combined across studies using standard inverse-variance fixed effects meta-analysis methods.

RESULTS: A total of 75 variants were genotyped/imputed successfully. Neither non-weighted nor weighted polygenic risk scores were associated with late radiation toxicity in individual studies (P>0.11) or after meta-analysis (P>0.24). No individual variant was associated with 2-year toxicity.

CONCLUSION: Patients with a high polygenic susceptibility for prostate cancer have no increased risk for developing late radiotherapy toxicity. These findings suggest that patients with a genetic predisposition for prostate cancer, inferred by common variants, can be safely treated using current standard radiotherapy regimens.

Original languageEnglish
Pages (from-to)1165-74
Number of pages10
JournalBr J Cancer
Issue number10
Early online date12 Apr 2016
Publication statusPublished - 10 May 2016


  • Aged
  • European Continental Ancestry Group
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Germ-Line Mutation
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Principal Component Analysis
  • Prostatic Neoplasms
  • Radiation Injuries
  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre


Dive into the research topics of 'Common genetic variation associated with increased susceptibility to prostate cancer does not increase risk of radiotherapy toxicity.'. Together they form a unique fingerprint.

Cite this