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

Istituto di Ematologia, Universita' Cattolica S. Cuore, Rome, Italy

Requests for reprints: Stefan Hohaus, Istituto di Ematologia, Universita' Cattolica S. Cuore L.go A. Gemelli, 1, 00168 Rome, Italy. Phone: 39-6-30154180; Fax: 39-6-35503777; E-mail: stefanhohaus{at}hotmail.com.

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 Ile¹⁰⁵Val 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 Ile¹⁰⁵Val 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 ¹⁰⁵Val/¹⁰⁵Val GSTP1 genotype was 100%, for heterozygous patients 74% (95% confidence interval, 56-85), and for patients homozygous for the ¹⁰⁵Ile/¹⁰⁵Ile 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.

Key Words: Hodgkin's lymphoma • GSTP1 • polymorphism • prognostic factors

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