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.
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.
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.
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.British Journal of Cancer advance online publication 12 April 2016; doi:10.1038/bjc.2016.94 www.bjcancer.com.
British journal of cancer. 2016 Apr 12 [Epub ahead of print]
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
The Institute of Cancer Research, Royal Marsden NHS Foundation Trust, 123 Old Brompton Road, London SW7 3RP, UK., Centre for Cancer Genetic Epidemiology, Strangeways Research Laboratory, Worts Causeway, Cambridge CB1 8RN, UK., Department of Radiation Oncology, University of Rochester Medical Centre, Saunders Research Building, 265 Crittenden Boulevard, Rochester, NY 14620, USA., Centre for Cancer Genetic Epidemiology, Strangeways Research Laboratory, Worts Causeway, Cambridge CB1 8RN, UK., Institute of Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Christie Hospital NHS Foundation Trust, Manchester M20 4BX, UK., Cross Cancer Institute, Edmonton, Alberta, Canada., Department of Radiation Oncology and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Fundación Pública Galega de Medicina Xenómica-SERGAS, Grupo de Medicina Xenómica-USC, IDIS, CIBERER, Santiago de Compostela 15706, Spain., Department of Radiation Oncology, USC University Hospital Complex, SERGAS, Santiago de Compostela, Spain., Centre for Cancer Genetic Epidemiology, Strangeways Research Laboratory, Worts Causeway, Cambridge CB1 8RN, UK., The Institute of Cancer Research, Royal Marsden NHS Foundation Trust, 123 Old Brompton Road, London SW7 3RP, UK., Clinical Trials and Statistics Unit, The Institute of Cancer Research, London SM2 5NG, UK., Clinical Trials Unit (CTU), Medical Research Council, London WC2B 6NH, UK., Department of Oncology, Addenbrookes Hospital, Hills Road, Cambridge CB2 0QQ UK., Centre for Cancer Genetic Epidemiology, Strangeways Research Laboratory, Worts Causeway, Cambridge CB1 8RN, UK., The Institute of Cancer Research, Royal Marsden NHS Foundation Trust, 123 Old Brompton Road, London SW7 3RP, UK., Institute of Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Christie Hospital NHS Foundation Trust, Manchester M20 4BX, UK.