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非裔美国男性和高加索裔男性转移性前列腺癌中胚系突变的比较。

Comparison of germline mutations in African American and Caucasian men with metastatic prostate cancer.

机构信息

Department of Medicine, Tulane Cancer Center, Tulane University, New Orleans, Louisiana, USA.

Genitourinary Oncology Section, Levine Cancer Institute/Atrium Health, Charlotte, North Carolina, USA.

出版信息

Prostate. 2021 May;81(7):433-439. doi: 10.1002/pros.24123. Epub 2021 Apr 1.

Abstract

BACKGROUND

The goal of this study is to evaluate germline genetic variants in African American men with metastatic prostate cancer as compared to those in Caucasian men with metastatic prostate cancer in an effort to understand the role of genetic factors in these populations.

METHODS

African American and Caucasian men with metastatic prostate cancer who had germline testing using multigene panels were used to generate comparisons. Germline genetic results, clinical parameters, and family histories between the two populations were analyzed.

RESULTS

A total of 867 patients were included in this retrospective study, including 188 African American and 669 Caucasian patients. There was no significant difference in the likelihood of a pathogenic or likely-pathogenic variants (PV/LPVs) between African American and Caucasian patients (p = .09). African American patients were more likely to have a variant of unknown significance than Caucasians (odds ratio [OR] = 1.95; p < .0001). BRCA1 PV/LPVs were higher in African Americans (OR = 4.86; p = .04). African American patients were less likely to have a PV/LPV in non-BRCA DNA repair genes (OR = 0.30; p = .008). Family history of breast (OR = 2.09; p = .002) or ovarian cancer (OR = 2.33; p = .04) predicted PV/LPVs in Caucasians but not African-Americans. This underscores the limitations of family history in AA men and the importance of personal history to guide germline testing in AA men.

CONCLUSIONS

In metastatic prostate cancer patients, PV/LPVs of tested genes did not vary by race, BRCA1 PV/LPVs were more common in the African American subset. However, PV/LPVs in non-BRCA DNA repair genes were less likely to be encountered in African Americans. Family history associated with genetic testing results in Caucasians only.

摘要

背景

本研究旨在评估转移性前列腺癌的非裔美国男性与转移性前列腺癌的白种男性之间的种系遗传变异,以了解遗传因素在这些人群中的作用。

方法

使用多基因panel 对患有转移性前列腺癌的非裔美国男性和白种男性进行种系检测,以此生成对比。分析两种人群的种系遗传结果、临床参数和家族史。

结果

本回顾性研究共纳入 867 例患者,包括 188 例非裔美国患者和 669 例白种患者。非裔美国患者和白种患者发生致病性或可能致病性变异(PV/LPVs)的可能性无显著差异(p=0.09)。非裔美国人发生意义不明变异的可能性高于白种人(优势比 [OR] = 1.95;p<0.0001)。BRCA1PV/LPVs 在非裔美国人中更高(OR=4.86;p=0.04)。非裔美国人发生非 BRCA 种系 DNA 修复基因的 PV/LPV 的可能性更低(OR=0.30;p=0.008)。家族史有乳腺癌(OR=2.09;p=0.002)或卵巢癌(OR=2.33;p=0.04)的白种人预测发生 PV/LPVs,但非裔美国人没有。这突出了家族史在非裔美国人中的局限性,以及个人史在指导非裔美国人种系检测中的重要性。

结论

在转移性前列腺癌患者中,检测基因的 PV/LPVs 不因种族而变化,BRCA1PV/LPVs 在非裔美国亚组中更为常见。然而,非 BRCA DNA 修复基因的 PV/LPVs 更不可能在非裔美国人中发生。只有白种人的家族史与基因检测结果相关。

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Racial Differences in Genomic Profiling of Prostate Cancer.前列腺癌基因组分析中的种族差异
N Engl J Med. 2020 Sep 10;383(11):1083-1085. doi: 10.1056/NEJMc2000069.
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Olaparib for Metastatic Castration-Resistant Prostate Cancer.奥拉帕利治疗转移性去势抵抗性前列腺癌。
N Engl J Med. 2020 May 28;382(22):2091-2102. doi: 10.1056/NEJMoa1911440. Epub 2020 Apr 28.
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Ethnic disparities among men with prostate cancer undergoing germline testing.男性前列腺癌患者进行种系检测的种族差异。
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