Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.5.2 (NQO1)
 6,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The last four decades have seen significant increase in the incidence of non-Hodgkin lymphoma (NHL) as a possible result of increasing environmental carcinogens exposure. Based on the increasing evidence for the association between carcinogen-exposure-related cancer risk and xenobiotic gene polymorphisms, we have undertaken a hospital based case-control study on xenobiotic gene polymorphisms in Saudi individuals with a diagnosis of diffuse large B-cell lymphoma (DLBCL). Polymorphisms in five genes (CYP1A1, GSTT1, GSTP1, GSTM1, and NQO1) were characterized in 182 individuals with DLBCL and 513 normal controls using PCR-RFLP method. The CYP1A1*2C (p = 0.011, OR: 6.62, and 95% CI: 1.56-28.10), GSTT1 null (p < or = 0.001, OR: 11.94, 95% CI: 7.88-18.12), and GSTP1 TT genotypes (p = 0.017, OR: 3.42, 95% CI 1.26-9.38) demonstrated significant association of DLBCL risk. None of the other alleles tested for proved to be significant indicators of DLBCL risk. Our findings suggest that polymorphisms of xenobiotic metabolizing enzyme genes may modify the individual susceptibility to develop DLBCL in Saudi Arabian population.
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PMID:Polymorphisms of drug-metabolizing enzymes CYP1A1, GSTT and GSTP contribute to the development of diffuse large B-cell lymphoma risk in the Saudi Arabian population. 1820 21

Aromatic amines (AAs) and polycyclic aromatic hydrocarbons (PAHs) are carcinogens present in tobacco smoke and functional polymorphisms in NAT2 and GSTM1 metabolizing genes are associated with increased bladder cancer risk. We evaluated whether genetic variation in other candidate metabolizing genes are also associated with risk. Candidates included genes that control the transcription of metabolizing genes [aryl hydrocarbon receptor (AHR), AHRR and aryl hydrocarbon nuclear translocator (ARNT)] and genes that activate/detoxify AA or PAH (AKR1C3, CYP1A1, CYP1A2, CYP1B1, CYP3A4, EPHX1, EPHX2, NQO1, MPO, UGT1A4, SULT1A1 and SULT1A2). Using genotype data from 1150 cases of urothelial carcinomas and 1149 controls from the Spanish Bladder Cancer Study, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) adjusting for age, gender, region and smoking status. Based on a test for trend, we observed 10 non-redundant single-nucleotide polymorphisms (SNPs) in five genes (AKR1C3, ARNT, CYP1A1, CYP1B1 and SULT1A2) significantly associated with bladder cancer risk. We observed an inverse association with risk for the AKR1C3 promoter SNP rs1937845 [OR (95% CI) for heterozygote and homozygote variant compared with common homozygote genotype were 0.86 (0.70-1.06) and 0.74 (0.57-0.96), respectively; P for trend = 0.02]. Interestingly, genetic variation in this region has been associated with lung, non-Hodgkin lymphoma and prostate cancer risk. Analysis of additional SNPs to capture most (approximately 90%) of common genetic variation in AKR1C3 and haplotype walking analyses based on all AKR1C3 SNPs (n = 25) suggest two separate regions associated with bladder cancer risk. These results indicate that genetic variation in carcinogen-metabolizing genes, particularly AKR1C3, could be associated with bladder cancer risk.
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PMID:Bladder cancer risk and genetic variation in AKR1C3 and other metabolizing genes. 1863 53

Therapy-related myeloid neoplasms (t-MN) include acute myeloid leukemias and myelodysplastic syndromes arising in patients who have been treated with chemotherapy, radiation therapy, immunosuppressive agents or after documented exposure to environmental carcinogen. t-MN are defined according to the primary treatment and the corresponding genetic and molecular lesions. Chromosome(s) 7 and/or 5 monosomies or deletions are typical of alkylating agent-induced AML, while balanced translocations involving chromosome bands 11q23 and 21q22 are associated to preceeding therapy with DNA-topoisomerase II inhibitors. Antimetabolites, and in particular the immunosuppressive agents azathioprine and fludarabine, have also been recently associated to t-MN. Leukemias developing after benzene exposure are similar to t-MN and are characterized by chromosomal aberrations, which have been also observed among otherwise healthy benzene-exposed workers. Individual predisposing factors, including polymorphisms of detoxification and DNA-repair enzymes have been identified. Two genetic variants in key metabolizing enzymes, myeloperoxidase and NAD(P)H:quinone oxidoreductase, have been shown to influence susceptibility to benzene hematotoxicity. Combination of polymorphisms impairing detoxification and DNA repair may significantly increase therapy-related myeloid neoplasm risk. Among hematological malignancies, long-term survivors of Hodgkin's lymphoma are exposed to an increased t-MN risk, particularly when receiving MOPP-based and escalated-BEACOPP regimens, and when alkylators are combined to radiotherapy. Patients with lymphoma are at highest risk if total body irradiation followed by autologous stem cell transplantation is used as rescue or consolidation. The addition of granulocyte-colony stimulating factor (G-CSF) and radiotherapy plays a significant role in t-MN following treatment of childhood acute lymphoblastic leukemia. In solid tumors, treatment for breast cancer and germ-cell tumors has been associated with a 1-5% lifetime risk of t-MN.
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PMID:Incidence and susceptibility to therapy-related myeloid neoplasms. 2002 17