PURPOSE We describe the pathogenic variant spectrum and identify predictors of positive results among men referred for clinical genetic testing for prostate cancer. METHODS One thousand eight hundred twelve men with prostate cancer underwent clinical multigene panel testing between April 2012 and September 2017. Stepwise logistic regression determined the most reliable predictors of positive results among clinical variables reported on test requisition forms. RESULTS A yield of 9.4-12.1% was observed among men with no prior genetic testing. In this group, the positive rate of BRCA1 and BRCA2 was 4.6%; the positive rate for the mismatch repair genes was 2.8%. Increasing Gleason score (odds ratio [OR] 1.19; 95% confidence interval [CI] 0.97-1.45); personal history of breast or pancreatic cancer (OR 3.62; 95% CI 1.37-9.46); family history of breast, ovarian, or pancreatic cancer (OR 2.32 95% CI 1.48-3.65); and family history of Lynch syndrome-associated cancers (OR 1.97; 95% CI 1.23-3.15) were predictors of positive results. CONCLUSION These results support multigene panel testing as the primary genetic testing approach for hereditary prostate cancer and are supportive of recommendations for consideration of germline testing in men with prostate cancer. Expanding the criteria for genetic testing should be considered as many pathogenic variants are actionable for treatment of advanced prostate cancer.

中文翻译：

---

诊断患有前列腺癌的男性的遗传性癌症倾向。


目的 我们描述了前列腺癌临床基因检测男性的致病变异谱并确定了阳性结果的预测因素。方法 2012 年 4 月至 2017 年 9 月期间，1812 名前列腺癌男性接受了临床多基因小组测试。逐步逻辑回归确定了测试申请表上报告的临床变量中阳性结果最可靠的预测因子。结果 在没有进行过基因检测的男性中，观察到的得率为 9.4-12.1%。本组BRCA1、BRCA2阳性率为4.6%；错配修复基因阳性率为2.8%。格里森评分增加（比值比 [OR] 1.19；95% 置信区间 [CI] 0.97-1.45）；乳腺癌或胰腺癌个人病史（OR 3.62；95% CI 1.37-9.46）；乳腺癌、卵巢癌或胰腺癌家族史（OR 2.32 95% CI 1.48-3.65）；林奇综合征相关癌症家族史（OR 1.97；95% CI 1.23-3.15）是阳性结果的预测因素。结论 这些结果支持多基因组检测作为遗传性前列腺癌的主要基因检测方法，并支持考虑对患有前列腺癌的男性进行种系检测的建议。应考虑扩大基因检测的标准，因为许多致病变异可用于治疗晚期前列腺癌。