Faculty of Medicine and Health Technology, Prostate Cancer Research Center, Tampere University, 33100 Tampere, Finland.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 17177 Stockholm, Sweden.
Genes (Basel). 2020 Mar 14;11(3):314. doi: 10.3390/genes11030314.
Germline variants in DNA repair genes are associated with aggressive prostate cancer (PrCa). The aim of this study was to characterize germline variants in DNA repair genes associated with lethal PrCa in Finnish and Swedish populations. Whole-exome sequencing was performed for 122 lethal and 60 unselected PrCa cases. Among the lethal cases, a total of 16 potentially damaging protein-truncating variants in DNA repair genes were identified in 15 men (12.3%). Mutations were found in six genes with (4.1%) and (3.3%) being most frequently mutated. Overall, the carrier rate of truncating variants in DNA repair genes among men with lethal PrCa significantly exceeded the carrier rate of 0% in 60 unselected PrCa cases ( = 0.030), and the prevalence of 1.6% ( < 0.001) and 5.4% ( = 0.040) in Swedish and Finnish population controls from the Exome Aggregation Consortium. No significant difference in carrier rate of potentially damaging nonsynonymous single nucleotide variants between lethal and unselected PrCa cases was observed ( = 0.123). We confirm that DNA repair genes are strongly associated with lethal PrCa in Sweden and Finland and highlight the importance of population-specific assessment of variants contributing to PrCa aggressiveness.
种系 DNA 修复基因变异与侵袭性前列腺癌（PrCa）相关。本研究旨在分析芬兰和瑞典人群中与致死性前列腺癌相关的种系 DNA 修复基因变异。对 122 例致死性和 60 例非选择性前列腺癌病例进行全外显子组测序。在致死性病例中，共发现 16 种潜在的导致蛋白截断的 DNA 修复基因突变，发生在 15 名男性中（12.3%）。突变发生在 6 个基因中，其中 （4.1%）和 （3.3%）突变频率最高。总的来说，致死性前列腺癌男性中 DNA 修复基因突变的携带者率显著高于 60 例非选择性前列腺癌病例（0%）的携带者率（ = 0.030），且在瑞典和芬兰人群对照中，携带率分别为 1.6%（ < 0.001）和 5.4%（ = 0.040）。在致死性和非致死性前列腺癌病例中，潜在有害非同义单核苷酸变异的携带者率无显著差异（ = 0.123）。本研究证实，在瑞典和芬兰，DNA 修复基因与致死性前列腺癌密切相关，突出了对导致前列腺癌侵袭性的变异进行特定人群评估的重要性。
