eprintid: 1505704 rev_number: 34 eprint_status: archive userid: 608 dir: disk0/01/50/57/04 datestamp: 2016-11-21 16:12:26 lastmod: 2021-12-02 00:20:30 status_changed: 2016-11-21 16:12:26 type: article metadata_visibility: show creators_name: Kerns, SL creators_name: Dorling, L creators_name: Fachal, L creators_name: Bentzen, S creators_name: Pharoah, PD creators_name: Barnes, DR creators_name: Gómez-Caamaño, A creators_name: Carballo, AM creators_name: Dearnaley, DP creators_name: Peleteiro, P creators_name: Gulliford, SL creators_name: Hall, E creators_name: Michailidou, K creators_name: Carracedo, Á creators_name: Sia, M creators_name: Stock, R creators_name: Stone, NN creators_name: Sydes, MR creators_name: Tyrer, JP creators_name: Ahmed, S creators_name: Parliament, M creators_name: Ostrer, H creators_name: Rosenstein, BS creators_name: Vega, A creators_name: Burnet, NG creators_name: Dunning, AM creators_name: Barnett, GC creators_name: West, CM creators_name: Radiogenomics Consortium, . title: Meta-analysis of Genome Wide Association Studies Identifies Genetic Markers of Late Toxicity Following Radiotherapy for Prostate Cancer ispublished: pub divisions: UCL divisions: B02 divisions: D65 divisions: J38 keywords: Cancer survivorship, Genome-wide association study, Prostate cancer, Quality of life, Radiation toxicity, Radiogenomics note: © 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). abstract: Nearly 50% of cancer patients undergo radiotherapy. Late radiotherapy toxicity affects quality-of-life in long-term cancer survivors and risk of side-effects in a minority limits doses prescribed to the majority of patients. Development of a test predicting risk of toxicity could benefit many cancer patients. We aimed to meta-analyze individual level data from four genome-wide association studies from prostate cancer radiotherapy cohorts including 1564 men to identify genetic markers of toxicity. Prospectively assessed two-year toxicity endpoints (urinary frequency, decreased urine stream, rectal bleeding, overall toxicity) and single nucleotide polymorphism (SNP) associations were tested using multivariable regression, adjusting for clinical and patient-related risk factors. A fixed-effects meta-analysis identified two SNPs: rs17599026 on 5q31.2 with urinary frequency (odds ratio [OR] 3.12, 95% confidence interval [CI] 2.08-4.69, p-value 4.16×10(-8)) and rs7720298 on 5p15.2 with decreased urine stream (OR 2.71, 95% CI 1.90-3.86, p-value=3.21×10(-8)). These SNPs lie within genes that are expressed in tissues adversely affected by pelvic radiotherapy including bladder, kidney, rectum and small intestine. The results show that heterogeneous radiotherapy cohorts can be combined to identify new moderate-penetrance genetic variants associated with radiotherapy toxicity. The work provides a basis for larger collaborative efforts to identify enough variants for a future test involving polygenic risk profiling. date: 2016-08 date_type: published official_url: http://doi.org/10.1016/j.ebiom.2016.07.022 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green article_type_text: Journal Article verified: verified_manual elements_id: 1143637 doi: 10.1016/j.ebiom.2016.07.022 pii: S2352-3964(16)30327-9 lyricists_name: Sydes, Matthew lyricists_id: MRSYD21 actors_name: Sydes, Matthew actors_id: MRSYD21 actors_role: owner full_text_status: public publication: EBioMedicine volume: 10 pagerange: 150-163 event_location: Netherlands issn: 2352-3964 citation: Kerns, SL; Dorling, L; Fachal, L; Bentzen, S; Pharoah, PD; Barnes, DR; Gómez-Caamaño, A; ... Radiogenomics Consortium, .; + view all <#> Kerns, SL; Dorling, L; Fachal, L; Bentzen, S; Pharoah, PD; Barnes, DR; Gómez-Caamaño, A; Carballo, AM; Dearnaley, DP; Peleteiro, P; Gulliford, SL; Hall, E; Michailidou, K; Carracedo, Á; Sia, M; Stock, R; Stone, NN; Sydes, MR; Tyrer, JP; Ahmed, S; Parliament, M; Ostrer, H; Rosenstein, BS; Vega, A; Burnet, NG; Dunning, AM; Barnett, GC; West, CM; Radiogenomics Consortium, .; - view fewer <#> (2016) Meta-analysis of Genome Wide Association Studies Identifies Genetic Markers of Late Toxicity Following Radiotherapy for Prostate Cancer. EBioMedicine , 10 pp. 150-163. 10.1016/j.ebiom.2016.07.022 <https://doi.org/10.1016/j.ebiom.2016.07.022>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/1505704/1/sydes_final_pdf__1-s2.0-S2352396416303279-main.pdf