1. ¹Division of Hematology Oncology, Cincinnati Children's Hospital Medical Center and Department of Pediatrics, University of Cincinnati, Cincinnati, OH, USA
2. ²Pediatric Hematology Oncology, University of Minnesota, Minneapolis, MN, USA
3. ³Statistics, Children's Oncology Group and Department of Epidemiology & Health Policy Research, University of Florida, Gainesville, FL, USA
4. ⁴Pediatric Hematology Oncology, University of Mississippi, Jackson, MS, USA

Correspondence: Dr PA Mehta, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, MLC 7015, Cincinnati, OH 45229, USA. E-mail: parinda.mehta@cchmc.org

Received 7 April 2006; Revised 20 May 2006; Accepted 22 May 2006; Published online 22 June 2006.

Abstract

Perforin plays a key role in the cytotoxicity of natural killer and cytotoxic T cells. Genetic mutations in the perforin gene (PRF1) give rise to approximately 30% cases of familial hemophagocytic lymphohistiocytosis. A frequent polymorphism, A91V (C to T transition at position 272), may impair processing of perforin protein to the active form, and has been suggested to increase susceptibility to childhood acute lymphoblastic leukemia (ALL). To investigate the role of A91V in ALL, we genotyped 2272 children with de novo ALL registered on the Pediatric Oncology Group ALL Classification study P9900 and 655 normal controls. Allele frequencies in the controls showed a very low frequency of the variant allele in blacks, 0.7% compared to 4% in white controls. In light of this, analysis was restricted to a comparison of white cases and controls only. Overall genotype frequencies were similar in white ALL cases and normal white controls (P=0.58), indicating that in contrast to the previous report, A91V polymorphism is not associated with increased risk of childhood ALL. PRF1 A91V frequency was significantly increased in children with BCR-ABL positive ALL (24 vs 8.5%; P=0.0048); however, this observation includes a relatively small number of cases and needs further exploration.