title: The TNF-alpha 238A polymorphism is associated with susceptibility to persistent bone marrow dysplasia following chronic exposure to benzene.
abstract: Chronic exposure to benzene can result in transient hematotoxicity (benzene poisoning, BP) or persistent bone marrow pathology including dysplasia and/or acute myeloid leukemia. We recently described a persistent bone marrow dysplasia with unique dysplastic and inflammatory features developing in individuals previously exposed to benzene (BID) [Irons RD, Lv L, Gross SA, Ye X, Bao L, Wang XQ, et al. Chronic exposure to benzene results in a unique form of dysplasia. Leuk Res 2005;29:1371-80]. In this study we investigated the association of single nucleotide polymorphisms (SNP) (-863 (C-->A), -857 (C-->T), -308 (G-->A), -238 (G-->A)) in the promoter region of the cytokine, tumor necrosis factor-alpha (TNF-alpha) on the development of BP, persistent BID and de novo myelodysplastic syndrome (MDS) in 394 individuals. Only the -238 (G-->A) polymorphism was significantly associated with the development of BID (odds ratio (OR)=7.4; 95% C.I. 1.23-44.7) and was specific for BID and not de novo MDS or BP. These findings are consistent with a role for inflammation in the development of BID and suggest that cell-specific alterations in TNF-alpha expression may promote clonal selection in the evolution of neoplastic hematopoietic disease.
authors: International Clinical and Molecular Research Center, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors: Ling
authors: L
authors: Lv
authors: Patrick
authors: P
authors: Kerzic
authors: Guowei
authors: G
authors: Lin
authors: A Robert
authors: AR
authors: Schnatter
authors: Liming
authors: L
authors: Bao
authors: Yongchen
authors: Y
authors: Yang
authors: Hejian
authors: H
authors: Zou
authors: Hua
authors: H
authors: Fu
authors: Xibao
authors: X
authors: Ye
authors: Sherilyn A
authors: SA
authors: Gross
authors: Thomas W
authors: TW
authors: Armstrong
authors: Richard D
authors: RD
authors: Irons
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D001554:Benzene / Q000633:toxicity*; D001853:Bone Marrow / Q000187:drug effects*; D017931:DNA Primers; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D017931:DNA Primers; D014409:Tumor Necrosis Factor-alpha; D001554:Benzene