CYP1AI, glutathione S-transferase gene polymorphisms and risk of Polycythemia vera.
BACKGROUND
Associations between polymorphisms for gene encoding enzymes involved in biotransformation of xenobiotics and susceptibility to several cancers have been shown in several studies. The aim of the present study was to evaluate the association of polymorphisms of cytochrome P450 (CYP1A1) and GST deletions with the incidence of Polycythemia vera (PV) among the Jordanian population.


METHODS
The study included 61 PV patients and 70 cancer-free healthy controls. CYP1A1 (m1, m2, m3, m4) and GST (T1, M1) genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism. The risk of cancer associated with gene polymorphisms was estimated by calculations of odds ratio (ORs) and confidence intervals (95% CIs) using Mantel-Haenszel statistics.


RESULTS
A statistically significant difference between the PV group and the control group was observed in the case of GSTM1 null genotype with 3.38 fold increase in risk of developing PV (95% CI=1.63-7.01, p=0.001) while GSTT1 null genotype showed no significance (OR=1.11; 95% CI=0.50-2.44, p=0.38). No significant association was found between the CYP1A1 mutant genotypes (m1, m2, m4) and PV. The m3 genotype was absent in both patients and controls. Interestingly, a substantial significant increase of PV risk for the combination of GSTM1 null genotype and CYP1A1 m1 (T6235C) genotype was observed (OR=4.38; 95% CI=1.15-16.73, p=.02). Furthermore, the present case-control study showed that the studied Jordanian population generally resembles Caucasian populations with respect to the frequencies of CYP1A1 polymorphisms.


CONCLUSIONS
Our data suggests that GSTM1 null genotype alone and in combination with CYP1A1 m1 genotype may be predisposing risk factors for PV in the Jordanian population.
Department of Physiology and Biochemistry, University of Jordan, Amman 11942, Jordan. rnaffa1410@yahoo.com
Randa G
RG
Naffa
Abdalla S
AS
Awidi
Al-Motassem F
AM
Yousef
Said I
SI
Ismail
D000328:Adult; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D011087:Polycythemia Vera / Q000201:enzymology* / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors
D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1