Genetic polymorphisms of biotransformation enzymes in patients with Hodgkin's and non-Hodgkin's lymphomas.
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.
Sarmanová
J
J
Biotransformations Group, Center of Occupational Diseases, National Institute of Public Health, Srobárova 48, Praha 10, 100 42, Czech Republic,.
Benesová
K
K
Gut
I
I
Nedelcheva-Kristensen
V
V
Tynková
L
L
Soucek
P
P
D000483:Alleles; D001711:Biotransformation; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004851:Epoxide Hydrolases / Q000235:genetics*; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D006689:Hodgkin Disease / Q000201:enzymology* / Q000235:genetics*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000201:enzymology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase; D004851:Epoxide Hydrolases