Perforin gene variation influences survival in childhood acute lymphoblastic leukemia

•Common perforin gene variants influence overall survival in childhood ALL.•rs885822 GG genotype was associated with worse outcome, independent of risk group.•Perforin gene variation may influence mortality in childhood ALL. Although a growing body of data links mutations in the perforin gene with increased susceptibility to hematologic malignancies, no studies discuss their influence on the clinical course of such diseases. The present study examines the impact of perforin gene variation on the clinical outcome in acute lymphoblastic leukemia (ALL) patients. The study enrolled 312 children aged 1–18 years, treated for ALL. PRF1 gene variants were analyzed through direct DNA sequencing. Variation in rs885822 was found to be associated with overall survival: patients carrying the GG genotype demonstrated a significantly increased risk of death compared to those carrying the A allele, independently of ALL risk groups (HR 3.13, 95%CI 1.16–7.8, p = 0.014). The effect was even more pronounced in high-risk ALL patients (p = 0.006). On the other hand, the presence of the rs35947132 minor A allele was slightly protective with regard to overall prognosis (p = 0.047). No differences in relapse-free survival were observed with regard to genotypes. The results of the study may imply that perforin gene variation has a role in modifying mortality in childhood ALL.