期刊
NATURE GENETICS
卷 46, 期 8, 页码 891-894出版社
NATURE PORTFOLIO
DOI: 10.1038/ng.3020
关键词
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资金
- CEGEN (Spanish National Genotyping Center)
- Instituto de Salud Carlos III [FIS PI10/00164, PI13/02030]
- Fondo Europeo de Desarrollo Regional [FEDER 2007-2013, PI13/01136]
- Isabel Barreto program from Xunta de Galicia
- Fondo Social Europeo
- ESTRO Technology Transfer Grant
- Cancer Research UK
- Experimental Cancer Medicine Centre funding
- National Institute for Health Research (NIHR) Royal Marsden NHS Foundation Trust
- Institute of Cancer Research Biomedical Research Centre
- Cancer Research UK [CRUK/06/16, SP2312/021, C8262/A7253]
- UK Department of Health
- NIHR Cancer Research Network
- American Cancer Society [RSGT-05-200-01-CCE]
- US Department of Defense [PC074201]
- US National Institutes of Health [1R01CA134444]
- Instituto de Salud Carlos III
- King Abdulaziz University grant [1-117-1434-HiCi]
- Innopharma and the Botin Foundation
- MRC [MC_UU_12023/6, MC_U122861330] Funding Source: UKRI
- Cancer Research UK [10588, 16565, 7253, 18504] Funding Source: researchfish
- Medical Research Council [MC_U122861330, MC_UU_12023/6, 1366822] Funding Source: researchfish
There is increasing evidence supporting the role of genetic variants in the development of radiation-induced toxicity(1). However, previous candidate gene association studies failed to elucidate the common genetic variation underlying this phenotype(2), which could emerge years after the completion of treatment(3). 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 Americas. One locus comprising TANC1 (lowest unadjusted P value for overall late toxicity = 6.85 x 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 x 10(-4), OR = 6.17,95% CI = 2.25-16.95; P-combined = 4.16 x 10(-10)). The inclusion of the third cohort gave unadjusted P-combined = 4.64 x 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.
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