Glutathione S-transferase P1 Genotype and Prognosis in Hodgkin's Lymphoma

Purpose: Glutathione S -transferase P1 (GSTP1) is a member of the GST enzyme superfamily that is important for the detoxification of several cytotoxic drugs and their by-products. 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 Ile 105 Val 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 Ile 105 Val 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 105 Val/ 105 Val GSTP1 genotype was 100%, for heterozygous patients 74% (95% confidence interval, 56-85), and for patients homozygous for the 105 Ile/ 105 Ile genotype 43% (95% confidence interval, 23-61). 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.