接受前列腺癌多基因检测的男性中的遗传性突变：对个性化前列腺癌基因评估的新启示。
Inherited Mutations in Men Undergoing Multigene Panel Testing for Prostate Cancer: Emerging Implications for Personalized Prostate Cancer Genetic Evaluation.
作者信息
Giri Veda N, Obeid Elias, Gross Laura, Bealin Lisa, Hyatt Colette, Hegarty Sarah E, Montgomery Susan, Forman Andrea, Bingler Ruth, Kelly William K, Dicker Adam P, Winheld Stephanie, Trabulsi Edouard J, Chen David Y T, Lallas Costas D, Allen Brian A, Daly Mary B, Gomella Leonard G
机构信息
, , , , , , , , , and , Thomas Jefferson University; , , , , , , and , Fox Chase Cancer Center, Philadelphia, PA; and , Myriad Genetics, Salt Lake City, UT.
出版信息
JCO Precis Oncol. 2017 May 4;1. doi: 10.1200/PO.16.00039. eCollection 2017 May.
PURPOSE
Multigene panels are commercially available for the evaluation of prostate cancer (PCA) predisposition, which necessitates tailored genetic counseling (GC) for men. Here we describe emerging results of Genetic Evaluation of Men, prospective multigene testing study in PCA to inform personalized genetic counseling, with emerging implications for referrals, cancer screening, and precision therapy.
PATIENTS AND METHODS
Eligibility criteria for men affected by or at high risk for PCA encompass age, race, family history (FH), and PCA stage/grade. Detailed demographic, clinical, and FH data were obtained from participants and medical records. Multigene testing was conducted after GC. Mutation rates were summarized by eligibility criteria and compared across FH data. The 95% CI of mutation prevalence was constructed by using Poisson distribution.
RESULTS
Of 200 men enrolled, 62.5% had PCA. Eleven (5.5%; 95% CI, 3.0% to 9.9%) had mutations; 63.6% of mutations were in DNA repair genes. FH of breast cancer was significantly associated with mutation status ( = .004), and FH that met criteria for hereditary breast and ovarian cancer syndrome was significantly associated with PCA (odds ratio, 2.33; 95% CI, 1.05 to 5.18). Variants of uncertain significance were reported in 70 men (35.0%). Among mutation carriers, 45.5% had personal/FH concordant with the gene. A tailored GC model was developed based on emerging findings.
CONCLUSION
Multigene testing for PCA identifies mutations mostly in DNA repair genes, with implications for precision therapy. The study highlights the importance of comprehensive genetic evaluation for PCA beyond metastatic disease, including early-stage disease with strong FH. Detailed FH is important for referrals of men for genetic evaluation. The results inform precision GC and cancer screening for men and their male and female blood relatives.
目的
多基因检测 panel 可用于评估前列腺癌（PCA）易感性，这就需要为男性提供个性化的遗传咨询（GC）。在此，我们描述了“男性遗传评估”这一 PCA 前瞻性多基因检测研究的初步结果，以指导个性化遗传咨询，并对转诊、癌症筛查和精准治疗产生新的影响。
患者与方法
PCA 患者或高危男性的纳入标准包括年龄、种族、家族史（FH）以及 PCA 分期/分级。从参与者和医疗记录中获取详细的人口统计学、临床和 FH 数据。在遗传咨询后进行多基因检测。根据纳入标准总结突变率，并在 FH 数据中进行比较。采用泊松分布构建突变患病率的 95%置信区间。
结果
在纳入的 200 名男性中，62.5%患有 PCA。11 名（5.5%；95%置信区间，3.0%至 9.9%）有突变；63.6%的突变位于 DNA 修复基因中。乳腺癌家族史与突变状态显著相关（P = 0.004），符合遗传性乳腺癌和卵巢癌综合征标准的家族史与 PCA 显著相关（优势比，2.33；95%置信区间，1.05 至 5.18）。70 名男性（35.0%）报告了意义未明的变异。在突变携带者中，45.5%的个人/家族史与基因相符。基于初步研究结果开发了一种个性化遗传咨询模型。
结论
PCA 的多基因检测主要在 DNA 修复基因中发现突变，这对精准治疗有影响。该研究强调了对 PCA 进行全面遗传评估的重要性，不仅包括转移性疾病，还包括具有强烈家族史的早期疾病。详细的家族史对于男性转诊进行遗传评估很重要。这些结果为男性及其男性和女性血亲的精准遗传咨询和癌症筛查提供了依据。
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