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

Research output: Contribution to journalArticle

  • External authors:
  • Mahbubl Ahmed
  • Leila Dorling
  • Sarah Kerns
  • Laura Fachal
  • Matt Partliament
  • Barry S Rosenstein
  • Ana Vega
  • Antonio Gómez-Caamaño
  • Gill Barnett
  • David P Dearnaley
  • Emma Hall
  • Matt Sydes
  • Paul D P Pharoah
  • Ros Eeles

Abstract

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.

Bibliographical metadata

Original languageEnglish
Pages (from-to)1165-74
Number of pages10
JournalBr J Cancer
Volume114
Issue number10
Early online date12 Apr 2016
DOIs
Publication statusPublished - 10 May 2016