Genetic polymorphisms of biotransformation enzymes in patients with Hodgkin's and non-Hodgkin's lymphomas.
OBJECTIVE
Considering the role in the metabolism of chemicals played by biotransformation enzymes, we aimed at determining whether any association exists between genetic polymorphisms in cytochromes p450 (CYP1A1 and CYP2E1), epoxide hydrolase (EPHX1), NAD(P)H: quinone oxidoreductase (NQO1), glutathione S-transferases (GSTs M1/P1/T1) and individual susceptibility to lymphomas.


METHODS
Genotyping assays based on polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were used to determine the frequency of polymorphisms in CYP1A1 (3'-flanking region), CYP2E1 (5'-flanking region and intron 6), EPHX1 (exon 3 and exon 4), NQO1 (exon 6), GSTM1 (deletion), GSTP1 (exon 5), and GSTT1 (deletion) in a case-control study composed of 219 patients with morbus Hodgkin (MH) and non-Hodgkin's lymphomas (NHL) and 455 age- and gender-matched healthy individuals.


RESULTS
Grading of NHL seemed to be associated with polymorphism in CYP2E1-intron 6 ( P=0.041). The EPHX1-exon 3 genotype distribution was significantly different between male controls and male patients with both kinds of lymphomas ( P=0.01) or with NHL ( P=0.019). The genotype GSTP1*2/*2 was prevalent in all MH (odds ratio (OR) =2.08, 95% confidence interval (CI) =1.05-4.14, P=0.035) and this difference was particularly evident in female subjects (OR=2.97, 95% CI=1.16-7.61, P=0.023). A significant difference in the distribution of GSTP1-exon 5 genotypes was found between NHL tumors larger vs. smaller than 5 cm ( P=0.03).


CONCLUSIONS
The results suggest that genetic polymorphisms of biotransformation enzymes may play a significant role in the development and progression of lymphoid malignancies.
Soucek
P
P
Biotransformations Group, Center of Occupational Diseases, National Institute of Public Health, Srobárova 48, Prague 10, 10042, Czech Republic. psoucek@szu.cz
Sarmanová
J
J
Kristensen
V N
VN
Apltauerová
M
M
Gut
I
I
D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics* / Q000494:pharmacology; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics* / Q000494:pharmacology; D004851:Epoxide Hydrolases / Q000235:genetics* / Q000494:pharmacology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics* / Q000494:pharmacology; D006689:Hodgkin Disease / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012737:Sex Factors
D019392:Cytochrome P-450 CYP2E1; D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase; D004851:Epoxide Hydrolases