Common genetic variation associated with increased susceptibility to prostate cancer does not increase risk of radiotherapy toxicity.
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<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.
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Genetic Predisposition to Disease
Polymorphism, Single Nucleotide
Principal Component Analysis
European Continental Ancestry Group
Genome-Wide Association Study
ICR-CTSU Urology and Head and Neck Trials Team
Clinical Academic Radiotherapy (Dearnaley)
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British journal of cancer, 2016, 114 (10), pp. 1165 - 1174