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首页> 外文期刊>British Journal of Cancer >Common genetic variation associated with increased susceptibility to prostate cancer does not increase risk of radiotherapy toxicity
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Common genetic variation associated with increased susceptibility to prostate cancer does not increase risk of radiotherapy toxicity

机译：与前列腺癌易感性增加相关的常见遗传变异不会增加放疗毒性的风险

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Background: 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. Methods: 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. Results: 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. Conclusion: 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.
机译：背景：许多种系单核苷酸多态性增加了对前列腺癌的敏感性，其中一些位于与细胞辐射反应有关的基因附近。这项研究调查了具有高遗传风险的前列腺癌患者在放疗后是否具有增加的毒性。方法：该研究包括来自四个放疗队列的1560名前列腺癌患者：RAPPER（n = 533），RADIOGEN（n = 597），GenePARE（n = 290）和CCI（n = 150）。来自全基因组关联研究的数据由1000个基因组参考小组估算。基于主成分分析，个体在遗传上与欧洲血统相似。使用多基因风险评分对遗传风险进行量化。回归模型测试了风险评分与2年毒性反应（总体，尿频，血流减少，直肠出血）之间的关联。使用标准的反方差固定效应荟萃分析方法将研究结果合并在一起。结果：成功地对75种变体进行了基因分型/推导。在个别研究中（P> 0.11）或在荟萃分析后（P> 0.24），未加权和加权多基因风险评分均与晚期放射毒性无关。没有个体变异与2年毒性相关。结论：对前列腺癌具有高多基因易感性的患者发生晚期放疗毒性的风险没有增加。这些发现表明，由普通变体推断出具有前列腺癌遗传易感性的患者可以使用当前的标准放疗方案进行安全治疗。

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