Lower overall survival in male patients with advanced disease undergoing allogeneic hematopoietic stem cell transplantation is associated with CYP1B1 Leu432Val polymorphism

Abstract

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 HSCT and their donors were genotyped for CYP1B1 (C432G) polymorphism by rt-PCR. 169 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=.006, unlike in donors. Five-year estimate for overall survival (OS) was 58% ±4 (CC) vs. 48% ±3 (CG and GG), p=.048. Surprisingly, this difference was only evident in males (p=.024): OS 58% ±6 vs. 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=.002): OS 44% ±8 (CC) vs. 32% ±6 (CG) vs. 6% ±6 (GG), whereas it was virtually absent in male patients with early disease. Oneyear non-relapse mortality (NRM) in male patients with AD was 8% ±4 (CC) vs. 21% ±5 (CG) vs. 50% ±12 (GG), p=.002. Three-year relapse rate in male patients with AD was 31% ±7 (wt) vs. 42% ±6 (mut), p=.04. Multivariate analysis for OS in male patients with AD revealed CYP1B1 polymorphism as the only prognostic factor: RR 1.78, p=.001. In conclusion, these results suggest that male patients with advanced disease and mutant CYP1B1 polymorphism have a lower OS after allogeneic HSCT due to a higher NRM and a higher relapse rate.