The potential risk of certain SNPs in EPHX1, NQO1, and PON1 genes among B-Non-Hodgkin Lymphoma patients: An Egyptian case-control study

Background: Xenobiotic metabolizing enzymes (XME) comprising epoxide hydrolase (EPHX1), NAD(P)H quinone-oxidoreductase 1 (NQO1) and paraoxonase 1 (PON1) are considered crucial for homeostasis and clearance of xenobiotics which involve external as well as internal carcinogens. Polymorphisms of xenobiotic-metabolizing genes are suggested to be implicated in the pathogenesis of various types of cancers. Aim of the work: The aim of the current study was to investigate the influence of inherited genetic polymorphisms of the xenobiotic metabolizing enzymes EPHX1, NQO1 and PON1 on the susceptibility and development of Non-Hodgkin's Lymphomas in a cohort of Egyptian population. Patients and methods: A total of 100 patients with B-non Hodgkin's lymphoma (B-NHL) with mean age of 52 years, together with 75 age and sex matched healthy controls were enrolled in the study for evaluation of Inherited genetic polymorphisms in the xenobiotic metabolizing enzymes EPHX1 (Tyr-His, rs 1,051,740), NQO1 (C609T rs 1,800,566) and PON1 (Codon 192) A-G, Gly (A)-Arg (B), re662 (Q192R) using Polymerase Chain Reaction Restriction Fragment Length Polymorphism (PCR- RFLP) assay. Results: The comparison between the distribution of the different genotypes of EPHX1 (T/C), NQO1 (C/T), PON1 (A/G) revealed no statistically significant difference between the patient and control groups except for the PON1 GG homozygote phenotype (p = 0.016). Further analysis of the influence of the studied genetic polymorphisms on the characteristics of the disease showed that there was no statistical difference between B-NHL patients harboring the wild or the polymorphic genotypes regarding their clinical status and laboratory data. Conclusion: The study suggests that there is no correlation between (EPHX1 and NQO1, PON1) genetic polymorphisms and the risk of B-NHL. However, In PON1 polymorphism, the homozygosity (GG) was significantly higher in the control group (13.3%) compared to B-NHL patients (3%) with a P-value = 0.016. So, better understanding of the functional consequences of EPHX1, NQO1 and PON1 genetic polymorphisms as well as involvement of larger cohort would provide a foundation for future studies of these genes in the pathogenesis of different types of NHL.