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.
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