There is increasing evidence supporting the role of genetic variants in the development of radiation-induced toxicity1. However, previous candidate gene association studies failed to elucidate the common genetic variation underlying this phenotype2, which could emerge years after the completion of treatment3. We performed a genome-wide association study on a Spanish cohort of 741 individuals with prostate cancer treated with external beam radiotherapy (EBRT). The replication cohorts consisted of 633 cases from the UK4 and 368 cases from North America5. One locus comprising TANC1 (lowest unadjusted P value for overall late toxicity = 6.85 × 10−9, odds ratio (OR) = 6.61, 95% confidence interval (CI) = 2.23–19.63) was replicated in the second stage (lowest unadjusted P value for overall late toxicity = 2.08 × 10−4, OR = 6.17, 95% CI = 2.25–16.95; Pcombined = 4.16 × 10−10). The inclusion of the third cohort gave unadjusted Pcombined = 4.64 × 10−11. These results, together with the role of TANC1 in regenerating damaged muscle, suggest that the TANC1 locus influences the development of late radiation-induced damage.
Access optionsAccess options
Subscribe to Journal
Get full journal access for 1 year
only $18.75 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
NCBI Reference Sequence
We are grateful to all participating patients for their cooperation. We thank I. Quintela from CEGEN (Spanish National Genotyping Center) for her support as Affymetrix genotyping platform manager. We also thank the Galician Supercomputation Centre for providing computing infrastructures and the Department of Scientific Computing at the Icahn School of Medicine at Mount Sinai for providing computational resources and staff expertise. This work was funded by grants from the Instituto de Salud Carlos III (FIS PI10/00164 and PI13/02030) and the Fondo Europeo de Desarrollo Regional (FEDER 2007–2013). L.F. is supported by the Isabel Barreto program from Xunta de Galicia and Fondo Social Europeo and was granted by an ESTRO Technology Transfer Grant (2012). The RAPPER group is supported by Cancer Research UK and Experimental Cancer Medicine Centre funding. Investigators from the Institute of Cancer Research and the Royal Marsden NHS Foundation Trust acknowledge support from the National Institute for Health Research (NIHR) Royal Marsden NHS Foundation Trust and The Institute of Cancer Research Biomedical Research Centre. Sample and data collection within the CHHiP trial (CRUK/06/16) were supported by Cancer Research UK (SP2312/021 and C8262/A7253) and the UK Department of Health, with patient recruitment at participating sites supported by the NIHR Cancer Research Network. B.S.R. and S.L.K. are funded by grants RSGT-05-200-01-CCE from the American Cancer Society, PC074201 from the US Department of Defense and 1R01CA134444 from the US National Institutes of Health. Á.C. acknowledges support from the Instituto de Salud Carlos III and the Fondo Europeo de Desarrollo Regional (PI13/01136, FEDER 2007–2013), a King Abdulaziz University grant (1-117-1434-HiCi), Innopharma and the Botin Foundation. The research collaboration leading to this paper was developed under the framework of the Radiogenomics Consortium.
Integrated supplementary information
Supplementary Tables 1–16, Supplementary Figures 1–12 and Supplementary Note
About this article
Multi-centre technical evaluation of the radiation-induced lymphocyte apoptosis assay as a predictive test for radiotherapy toxicity
Clinical and Translational Radiation Oncology (2019)