title: Possible Role of Polymorphisms in TNFA, NFKB1, and CASP8 Gene Promoter Areas in the Development of Chronic Lymphocytic Leukemia.
abstract: We studied the relationship between polymorphisms rs1800629 (-308G>A), rs28362491 (-94ins>del), and rs3834129 (-652ins>del) in the promoter regions of TNFA, NFKB1, and CASP8 genes, respectively, encoding TNF-α, nuclear transcription factor κB1 (NF-κB1), and caspase 8 (CASP8), and the risk and stages of chronic lymphocytic leukemia in ethnic Russians, residents of the Vyatka region of Russia. Allele -308A, genotype -308AA, and -308A genotypes (-308AA/-308AG) were associated with the risk of this pathology (OR=1.64, 95%CI 1.14-2.37, p=0.007; OR=4.48, 95%CI 1.20-16.80, p=0.02, and OR=1.57, 95%CI 1.05-2.36, p=0.03). In addition, NFKB1 allele -94del and genotype -94del/del were associated with advanced stages of the disease at the time of diagnosis (OR=0.66, 95%CI 0.46-0.97, p=0.03 and OR=0.43, 95%CI 0.20-0.92, p=0.03). These data suggest that -308G>A and -94ins>del polymorphisms of genes TNFA and NFKB1, respectively, can be involved in the pathogenesis of chronic lymphocytic leukemia.
authors.affiliation: Kirov Research Institute of Hematology and Blood Transfusion, Federal Medical-Biological Agency of Russia, Kirov, Russia. vovsepyan@mail.ru.
authors.forename: V A
authors.initials: VA
authors.lastname: Ovsepyan
authors.affiliation: Kirov Research Institute of Hematology and Blood Transfusion, Federal Medical-Biological Agency of Russia, Kirov, Russia.
authors.forename: A A
authors.initials: AA
authors.lastname: Shubenkina
authors.affiliation: Kirov Research Institute of Hematology and Blood Transfusion, Federal Medical-Biological Agency of Russia, Kirov, Russia.
authors.forename: E N
authors.initials: EN
authors.lastname: Zotova
mesh_terms: D016022:Case-Control Studies; D053181:Caspase 8 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D052002:NF-kappa B p50 Subunit / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D065840:Protective Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; C505530:CASP8 protein, human; D053181:Caspase 8
keywords: CASP8; NFKB1; TNFA; chronic lymphocytic leukemia; polymorphisms