International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University in Szczecin, Szczecin, Poland.
Department of Clinical Genetics and Pathology, University of Zielona Góra, Zielona Góra, Poland.
Br J Cancer. 2021 Aug;125(4):569-575. doi: 10.1038/s41416-021-01410-0. Epub 2021 May 18.
The objective of this study was to establish the contribution of PALB2 mutations to prostate cancer risk and to estimate survival among PALB2 carriers.
We genotyped 5472 unselected men with prostate cancer and 8016 controls for two Polish founder variants of PALB2 (c.509_510delGA and c.172_175delTTGT). In patients with prostate cancer, the survival of carriers of a PALB2 mutation was compared to that of non-carriers.
A PALB2 mutation was found in 0.29% of cases and 0.21% of controls (odds ratio (OR) = 1.38; 95% confidence interval (CI) 0.70-2.73; p = 0.45). PALB2 mutation carriers were more commonly diagnosed with aggressive cancers of high (8-10) Gleason score than non-carriers (64.3 vs 18.1%, p < 0.0001). The OR for high-grade prostate cancer was 8.05 (95% CI 3.57-18.15, p < 0.0001). After a median follow-up of 102 months, the age-adjusted hazard ratio for all-cause mortality associated with a PALB2 mutation was 2.52 (95% CI 1.40-4.54; p = 0.0023). The actuarial 5-year survival was 42% for PALB2 carriers and was 72% for non-carriers (p = 0.006).
In Poland, PALB2 mutations predispose to an aggressive and lethal form of prostate cancer.
本研究旨在确定 PALB2 突变对前列腺癌风险的贡献，并估计 PALB2 携带者的生存情况。
我们对 5472 名未经选择的前列腺癌患者和 8016 名对照者进行了两种波兰常见的 PALB2 突变（c.509_510delGA 和 c.172_175delTTGT）的基因分型。在前列腺癌患者中，比较了 PALB2 突变携带者与非携带者的生存情况。
在病例组中发现了 0.29%的 PALB2 突变，而在对照组中发现了 0.21%（比值比（OR）=1.38；95%置信区间（CI）0.70-2.73；p=0.45）。PALB2 突变携带者更常见被诊断为高级别（8-10 级）高评分（8-10）的侵袭性癌症，而非携带者为 18.1%（64.3%比 18.1%，p<0.0001）。高级别前列腺癌的 OR 为 8.05（95%CI 3.57-18.15，p<0.0001）。在中位随访 102 个月后，PALB2 突变与全因死亡率相关的年龄调整危险比为 2.52（95%CI 1.40-4.54；p=0.0023）。PALB2 携带者的 5 年生存率为 42%，而非携带者为 72%（p=0.006）。
在波兰，PALB2 突变易导致侵袭性和致命形式的前列腺癌。
