前列腺癌的遗传风险预测：对早期检测和预防的影响。

Genetic Risk Prediction for Prostate Cancer: Implications for Early Detection and Prevention.

机构信息

University of California San Diego, La Jolla, CA, USA.

University of California Los Angeles, Los Angeles, CA, USA.

出版信息

Eur Urol. 2023 Mar;83(3):241-248. doi: 10.1016/j.eururo.2022.12.021. Epub 2023 Jan 4.

DOI:10.1016/j.eururo.2022.12.021

PMID:36609003

Abstract

CONTEXT

Prostate cancer (PCa) is a leading cause of death and partially heritable. Genetic risk prediction might be useful for strategies to reduce PCa mortality through early detection and prevention.

OBJECTIVE

To review evidence for genetic risk prediction for PCa.

EVIDENCE ACQUISITION

A collaborative literature review was conducted using PubMed and Google Scholar. Search terms included genetic, risk, prediction, and "prostate cancer". Articles addressing screening, early detection, or prevention were prioritized, as were studies involving diverse populations.

EVIDENCE SYNTHESIS

Rare pathogenic mutations (RPMs), especially in DNA damage repair genes, increase PCa risk. RPMs in BRCA2 are most clearly deleterious, conferring 2-8.6 times higher risk of PCa and a higher risk of aggressive disease. Common genetic variants can be combined into genetic risk scores (GRSs). A high GRS (top 20-25% of the population) confers two to three times higher risk of PCa than average; a very high GRS (top 1-5%) confers six to eight times higher risk. GRSs are not specific for aggressive PCa, possibly due to methodological limitations and/or a field effect of an elevated risk for both low- and high-grade PCa. It is challenging to disentangle genetics from structural racism and social determinants of health to understand PCa racial disparities. GRSs are independently associated with a lethal PCa risk after accounting for family history and race/ancestry. Healthy lifestyle might partially mitigate the risk of lethal PCa.

CONCLUSIONS

Genetic risk assessment is becoming more common; implementation studies are needed to understand the implications and to avoid exacerbating healthcare disparities. Men with a high genetic risk of PCa can reasonably be encouraged to adhere to a healthy lifestyle.

PATIENT SUMMARY

Prostate cancer risk is inherited through rare mutations and through the combination of hundreds of common genetic markers. Some men with a high genetic risk (especially BRCA2 mutations) likely benefit from early screening for prostate cancer. The risk of lethal prostate cancer can be reduced through a healthy lifestyle.

摘要

背景

前列腺癌（PCa）是导致死亡的主要原因之一，且部分遗传。遗传风险预测可能有助于通过早期检测和预防来降低 PCa 的死亡率。

目的

回顾前列腺癌遗传风险预测的证据。

证据获取

使用 PubMed 和 Google Scholar 进行了合作文献综述。搜索词包括遗传、风险、预测和“前列腺癌”。优先考虑涉及筛查、早期检测或预防的文章，以及涉及不同人群的研究。

证据综合

罕见的致病性突变（RPM），尤其是在 DNA 损伤修复基因中，会增加 PCa 的风险。BRCA2 中的 RPM 最明显是有害的，使 PCa 的风险增加 2-8.6 倍，并增加侵袭性疾病的风险。常见的遗传变异可以组合成遗传风险评分（GRS）。高 GRS（人群的前 20-25%）比平均水平高出 2-3 倍的 PCa 风险；非常高的 GRS（前 1-5%）使 PCa 的风险增加 6-8 倍。GRS 对于侵袭性 PCa 并不特异，这可能是由于方法学上的限制和/或对低级别和高级别 PCa 的风险升高的场效应。要了解 PCa 种族差异，就需要从结构种族主义和健康的社会决定因素中理清遗传因素。GRS 在考虑家族史和种族/祖先后，与致命性 PCa 的风险独立相关。健康的生活方式可能部分减轻致命性 PCa 的风险。