The TNF-α 238A polymorphism is associated with susceptibility to persistent bone marrow dysplasia following chronic exposure to benzene
✍ Scribed by Ling Lv; Patrick Kerzic; Guowei Lin; A. Robert Schnatter; Liming Bao; Yongchen Yang; Hejian Zou; Hua Fu; Xibao Ye; Sherilyn A. Gross; Thomas W. Armstrong; Richard D. Irons
- Publisher
- Elsevier Science
- Year
- 2007
- Tongue
- English
- Weight
- 136 KB
- Volume
- 31
- Category
- Article
- ISSN
- 0145-2126
No coin nor oath required. For personal study only.
✦ Synopsis
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.