DLBCL is the most common subtype of NHL in adults. The efficacy of chemotherapy in DLBCL patients has significantly increased in the last 10 years. Growing evidence has shown genetic and environmental factors are involved in the etiology and prognosis of DLBCL. Genetic polymorphisms can influence the individual susceptibility and clinical outcome for different types of Lymphomas. The aim of this study was to investigate the genetic polymorphism of glutathione S-transferase P1 (GSTP1), as a prognostic factor for patients with DLBCL.
136 patients with DLBCL, 56 men and 80 women, median age - 47 y.o were included in the study. The patients received R-CHOP-like regimens. Genomic DNA was extracted from blood samples. GSTP1 polymorphism (c. 313 A > G, p. Ile105Val) were analyzed by Allelic Discrimination Real-Time PCR.
A homozygous for the A313A GSTP1 genotype was detected in 65/136 (47.8%) patients, heterozygous A313G – in 57/136 (42%) and 14/136 (10.2%) were homozygous for the G313G genotype of DLBCL (p < 0.05). The GSTP1 genotype distribution was conformed to Hardy-Weinberg equilibrium (χ2=0.05;p=1.01). The frequency of the homozygous wild genotype of the GSTP1 was significantly higher in patients with advanced disease vs patients with early stages of DLBCL (57% vs 43%, p < 0.05). The ORR was 76% (104/136) during the follow-up (median – 16 months; range 25–96 months), 41% of patients (56/136) had relapse or progression and 42 (31%) of them died during the follow-up period. We found an association of GSTP1 homozygous wild genotype with an unfavorable prognosis of DLBCL. The A313A genotype was strongly associated with increased risk of the DLBCL r/r disease as compared with A313G or G313G genotypes (23% vs 14% vs 4%, respectively, p < 0.05). 5-years EFS for patients with A313A GSTP1 genotype was lower compared to patients with A313G or G313G genotypes (42 % vs 52%, p < 0.05). Thus, the A313A genotype impacts survival of DLBCL.
Results suggest the genotype of the GSTP1 (A313A) is associated with unfavorable prognosis of DLBCL, reduce EFS rate. Results can be promising, but further investigations might provide a possible application of this marker as a prognostic factor of DLBCL.
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All authors have declared no conflicts of interest.