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Glutathione S-transferase P 1 Genotype and Prognosis in Hodgkin ’ s Lymphoma

Purpose: Glutathione S-transferase P1 (GSTP1) is a member of the GSTenzyme superfamily that is important for the detoxification of several cytotoxic drugs and their byproducts. A single nucleotide polymorphism results in the substitution of isoleucine (Ile) to valine (Val) at codon 105, causing a metabolically less active variant of the enzyme. We assessed the impact of the GSTP1 codon 105 genotype on treatment outcome in patients with Hodgkin’s lymphoma. Experimental Design: The IleVal polymorphism in the GSTP1 gene was analyzed using a PCR-RFLP technique. Ninety-seven patients with Hodgkin’s lymphoma were included and associations with patient characteristics and treatment outcome were analyzed. Results: The GSTP1 IleVal polymorphism was associated in a dose-dependent fashion with an improved failure-free survival in patients with Hodgkin’s lymphoma (P = 0.02). The probability of 5-year survival for patients homozygous for the Val/Val GSTP1 genotype was 100%, for heterozygous patients 74% (95% confidence interval, 56-85), and for patients homozygous for the Ile/Ile genotype 43% (95% confidence interval, 2361). The Cox multivariate analysis showed that GSTP1 codon 105 genotype was an independent prognostic factor. Conclusions: The GSTP1 genotype predicts clinical outcome in patients with Hodgkin’s lymphoma.