A three-stage genome-wide association study identifies a susceptibility locus for late radiotherapy toxicity at 2q24.1
Menée sur une cohorte espagnole incluant 741 patients atteints d'un cancer de la prostate traité par radiothérapie externe puis sur deux cohortes de réplication incluant au total 1 001 autres patients, cette étude d'association sur le génome entier identifie sur le chromosome 2q24.1 un locus de susceptibilité associé à la toxicité à long terme de la radiothérapie
There is increasing evidence supporting the role of genetic variants in the development of radiation-induced toxicity. However, previous candidate gene association studies failed to elucidate the common genetic variation underlying this phenotype, which could emerge years after the completion of treatment. 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 UK and 368 cases from North America. 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 TANC in regenerating damaged muscle, suggest that the TANC locus influences the development of late radiation-induced damage.