4.5 Article

Genetic polymorphisms of biotransformation enzymes in patients with Hodgkin's and non-Hodgkin's lymphomas

Journal

HUMAN MOLECULAR GENETICS
Volume 10, Issue 12, Pages 1265-1273

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/hmg/10.12.1265

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Considering the role in the metabolism of chemicals played by biotransformation enzymes, we aimed at determining whether any association exists between genetic polymorphisms in CYP1A1, CYP2E1,epoxide hydrolase (EPHX), glutathione S-transferases (GSTM1/P1/T1) and individual susceptibility to lymphomas, PCR-RFLP-based genotyping assays were used to determine the frequency of polymorphisms in CYP1A1(3 ' -flanking region), CYP2E1 (5 ' -flanking region and intron 6), EPHX (exons 3 and 4), GSTM1 (deletion), GSTP1 (exon 5) and GSTT1 (deletion) in a case-control study comprised of 219 patients with morbus Hodgkin (MH) and non-Hodgkin's lymphomas (NHL) and 455 age- and sex-matched healthy individuals. The distribution of genotypes in CYP2E1-intron 6 was significantly different between the control group and all lymphomas (P = 0.03), patients with NHL (P = 0.024), and especially aggressive diffuse NHL (P = 0.007), Grading of NHL seemed to be associated with this polymorphism as well (P = 0.041), The EPHX-exon 3 genotype distribution was significantly different between control males and males with all lymphomas (P = 0.01) or with NHL (P = 0.019), The Val/Val genotype of GSTP1-exon 5 was prevalent in all MH [odds ratio (OR) = 2,08, 95% confidence interval (CI) = 1.05-4.14] and this difference was particularly evident in females (OR = 2,97, 95% CI = 1.16-7.61), A significant difference in the distribution of GSTP1-exon 5 genotypes was found between NHL tumors >5 cm and those <5 cm (P = 0.03), The results suggest that genetic polymorphisms of biotransformation enzymes may play a significant role in the development of lymphoid malignancies.

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