The association of BRCA1 and BRCA2 mutations with prostate cancer risk, frequency, and mortality: A meta-analysis
The association of BRCA1 and BRCA2 mutations with prostate cancer risk, frequency, and mortality: A meta-analysis
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DOI：
10.1002/pros.23795
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发表时间：
2019-06-01
期刊：
影响因子：
2.8
通讯作者：
Abraham, Ivo
中科院分区：
文献类型：
--
作者：
Oh, Mok;Alkhushaym, Nasser;Abraham, Ivo
背景 先前的荟萃分析发现 BRCA1 突变与前列腺癌 (PCa) 之间没有关联。随后的 BRCA2 突变研究表明与 PCa 风险和死亡率相关。我们对总体 BRCA 突变携带者和亚组进行了荟萃分析，以 (1) 估计 BRCA 突变携带者中的 PCa 风险，(2) 评估 PCa 患者中 BRCA 突变携带者的频率，以及 (3) 比较 BRCA 突变携带者和非携带者之间的癌症特异性生存 (CSS) 和总生存 (OS)。方法 我们检索了 PubMed/MEDLINE、Embase 和 Cochrane 数据库。未调整的比值比 (OR)、百分比 (%) 和风险比 (HR) 分别用于计算 PCa 风险、频率和生存率的汇总估计值。针对这三个目标进行了按突变类型（BRCA1 或 BRCA2）的亚组分析。根据研究设计（年龄性别调整或粗略）、确定方法（确定或推断的基因分型）、人群（德系犹太人或普通人群）和生存结果（CSS 或 OS）进行了进一步的亚组分析。这些关联是使用随机效应模型在双边统计检验中进行评估的。结果 共纳入 8 个队列研究、7 个病例对照研究、4 个病例系列研究、28 个频率研究和 11 个生存研究。作为 BRCA 突变携带者（BRCA1 和/或 BRCA2）与 PCa 风险显着增加相关（OR = 1.90，95% CI = 1.58-2.29），与 BRCA1 突变（OR = 1.35，95% CI = 1.58-2.29）相比，BRCA2 突变与 PCa 风险更大（OR = 2.64，95% CI = 2.03-3.47）相关。 1.03-1.76）。 PCa患者中BRCA1和BRCA2携带者的频率分别为0.9%和2.2%。与非携带者相比，BRCA2 携带者的 OS（HR = 2.21，95% CI = 1.64-2.30）和 CSS（HR = 2.63，95% CI = 2.00-3.45）明显较差，而 OS（HR = 0.47，95% CI = 0.11-1.99）和 CSS（HR = 1.07，95% CI = 0.38-2.96) 是 比较 BRCA1 携带者和非携带者时，统计学上不显着。结论 整体 BRCA 突变携带者患 PCa 的风险增加 1.90 倍。 PCa 风险升高的主要原因是 BRCA2 携带者患 PCa 的风险高出 2.64 倍，而 BRCA1 携带者患 PCa 的风险则高出 1.35 倍。 PCa 患者中 BRCA2 突变频率高于 BRCA1 突变。 BRCA2 而非 BRCA1 突变与较高的 PCa 死亡率相关。 BRCA 突变可能是对高危患者进行分层的临床因素，并指导临床策略对 PCa 患者进行更有效的治疗。
Background A prior meta-analysis found no association between BRCA1 mutation and prostate cancer (PCa). Subsequent BRCA2 mutation studies have shown an association with PCa risk and mortality. We conducted a meta-analysis of overall BRCA mutation carriers and in subgroups to (1) estimate PCa risk in BRCA mutation carriers, (2) evaluate the frequency of BRCA mutation carriers in patients with PCa, and (3) compare cancer-specific survival (CSS) and overall survival (OS) among BRCA mutation carriers and noncarriers. Methods We searched the PubMed/MEDLINE, Embase, and Cochrane databases. Unadjusted odds ratio (OR), percentage (%), and hazard ratio (HR) were used to calculate pooled estimates for PCa risk, frequency, and survival, respectively. Subgroup analyses by mutation type (BRCA1 or BRCA2) were conducted for the three objectives. Further subgroup analyses by study design (age-sex-adjusted or crude), ascertainment method (ascertained or inferred genotyping), population (Ashkenazi Jewish or general population), and survival outcomes (CSS or OS) were conducted. The associations were evaluated using random-effects models, in two-sided statistical tests. Results A total of 8 cohort, 7 case-control, 4 case-series, 28 frequency, and 11 survival studies were included. Being a BRCA mutation carrier (BRCA1 and/or BRCA2) was associated with a significant increase in PCa risk (OR = 1.90, 95% CI = 1.58-2.29), with BRCA2 mutation being associated with a greater risk of PCa (OR = 2.64, 95% CI = 2.03-3.47) than BRCA1 (OR = 1.35, 95% CI = 1.03-1.76). The frequency of BRCA1 and BRCA2 carriers in patients with PCa was 0.9% and 2.2%, respectively. OS (HR = 2.21, 95% CI = 1.64-2.30) and CSS (HR = 2.63, 95% CI = 2.00-3.45) were significantly worse among BRCA2 carriers compared to noncarriers, whereas OS (HR = 0.47, 95% CI = 0.11-1.99) and CSS (HR = 1.07, 95% CI = 0.38-2.96) were statistically not significant when comparing BRCA1 carriers and noncarriers. Conclusions There is a 1.90-fold greater risk of PCa in overall BRCA mutation carriers. This elevated PCa risk is attributable mainly to a 2.64-fold greater risk of PCa in BRCA2 carriers compared to a moderate 1.35-fold greater risk in BRCA1 carriers. The frequency of BRCA2 mutations was higher than BRCA1 mutations among patients with PCa. BRCA2 but not BRCA1 mutations were associated with higher PCa mortality. The BRCA mutation may be a clinical factor to stratify high-risk patients and guide clinical strategies for more effective treatments for patients with PCa.