Ahmed, M;
Dorling, L;
Kerns, S;
Fachal, L;
Elliott, R;
Partliament, M;
Rosenstein, BS;
... West, CM; + view all
(2016)
Common genetic variation associated with increased susceptibility to prostate cancer does not increase risk of radiotherapy toxicity.
British Journal of Cancer
, 114
pp. 1165-1174.
10.1038/bjc.2016.94.
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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.
| Type: | Article |
|---|---|
| Title: | Common genetic variation associated with increased susceptibility to prostate cancer does not increase risk of radiotherapy toxicity. |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/bjc.2016.94 |
| Publisher version: | http://dx.doi.org/10.1038/bjc.2016.94 |
| Language: | English |
| Additional information: | This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Prostate cancer; genetic variants; radiotherapy; late toxicity |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1485884 |
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