Department of Bone Marrow Transplantation, West German Cancer Center, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany; Third Medical Department with Hematology, Medical Oncology, Hemostaseology, Infectious Diseases and Rheumatology, Paracelsus Medical University, Salzburg.
Department of Bone Marrow Transplantation, West German Cancer Center, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany; Department of Hygiene and Environmental Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany; Institute for Laboratory Medicine and Transfusion Medicine, Zotzô€€€Klimas, Düsseldorf.
Haematologica. 2024 Mar 1;109(3):799-808. doi: 10.3324/haematol.2023.283649.
Human cytochrome P450 1B1 (CYP1B1) is an extrahepatic key enzyme involved in estrogen metabolism, steroid synthesis, and pro-carcinogen activation. In a single-center retrospective study, 382 patients who underwent allogeneic hematopoetic stem cell transplantation and their donors were genotyped for CYP1B1 C432G polymorphism by reverse transcription polymerase chain reaction. One hundred and sixty-nine patients (44%) were homozygous wild-type (wt) gene CC, 157 (41%) heterozygous CG and 56 (15%) homozygous gene mutated GG. Of interest, mutated CYP1B1 was more common in male (62%) than in female patients (48%) P=0.006, unlike in donors. Five-year estimate for overall survival (OS) was 58±4% (CC) versus 48±3% (CG and GG), P=0.048. Surprisingly, this difference was only evident in males (P=0.024): OS 58±6% versus 42±4%, whereas it was virtually absent in females. Importantly, this difference was only evident in male patients with advanced disease (AD) (n=118, P=0.002): OS 44±8% (CC) versus 32±6% (CG) versus 6±6% (GG), whereas it was virtually absent in male patients with early disease. One-year non-relapse mortality in male patients with AD was 8±4% (CC) versus 21±5% (CG) versus 50±12% (GG), P=0.002. Three-year relapse rate in male patients with AD was 31±7% (wt) versus 42±6% (mut), P=0.04. Multivariate analysis for OS in male patients with AD revealed CYP1B1 polymorphism as the only prognostic factor: RR 1.78, P=0.001. In conclusion, these results suggest that male patients with AD and mutant CYP1B1 polymorphism have lower OS after allogeneic hematopoetic stem cell transplantation due to a higher non-relapse mortality and a higher relapse rate.
人类细胞色素 P450 1B1（CYP1B1）是一种肝外关键酶，参与雌激素代谢、类固醇合成和前致癌剂激活。在一项单中心回顾性研究中，通过逆转录聚合酶链反应对接受同种异体造血干细胞移植的 382 名患者及其供体进行 CYP1B1 C432G 多态性基因分型。169 名患者（44%）为纯合野生型（wt）基因 CC，157 名（41%）为杂合 CG，56 名（15%）为纯合基因突变 GG。有趣的是，突变 CYP1B1 在男性（62%）中比女性（48%）更常见，P=0.006，而在供体中则不同。总生存率（OS）的 5 年估计值为 58±4%（CC）与 48±3%（CG 和 GG），P=0.048。出乎意料的是，这种差异仅在男性中明显（P=0.024）：OS 58±6%与 42±4%，而在女性中则几乎不存在。重要的是，这种差异仅在患有晚期疾病（AD）的男性患者中明显（n=118，P=0.002）：OS 44±8%（CC）与 32±6%（CG）与 6±6%（GG），而在患有早期疾病的男性患者中则几乎不存在。患有 AD 的男性患者的 1 年非复发死亡率为 8±4%（CC）与 21±5%（CG）与 50±12%（GG），P=0.002。患有 AD 的男性患者的 3 年复发率为 31±7%（wt）与 42±6%（mut），P=0.04。对患有 AD 的男性患者的 OS 进行多变量分析显示，CYP1B1 多态性是唯一的预后因素：RR 1.78，P=0.001。总之，这些结果表明，患有 AD 的男性患者携带突变 CYP1B1 多态性，由于非复发死亡率较高和复发率较高，异体造血干细胞移植后 OS 较低。
