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

Abstract

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.