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Tumor Necrosis Factor-Alpha Polymorphisms in Ulcerative Colitis-Associated Colorectal Cancer.
- Source :
-
American Journal of Gastroenterology (Springer Nature) . Feb2008, Vol. 103 Issue 2, p407-415. 9p. 1 Black and White Photograph, 5 Charts, 1 Graph. - Publication Year :
- 2008
-
Abstract
- OBJECTIVES: Ulcerative colitis (UC) is characterized by chronic recurrent mucosal inflammation. Genetic studies in UC have indicated linkage to chromosome 6 in the region of the tumor necrosis factor-alpha (TNF-α) gene, a potent proinflammatory cytokine. TNF-α production is influenced by multiple factors including the type of immune cell and its level of activation. However, several single nucleotide polymorphisms (SNP) in the promoter region of TNF-α have been correlated with either increased or decreased production, indicating that regulation of TNF-α is in part genetic. Because UC patients are at increased risk for developing colorectal cancer (CRC), we investigated if there was an association between SNPs in the promoter of the TNF-α gene and UC-CRC. METHODS: DNA was extracted from formalin-fixed, paraffin-embedded tissue from 114 UC-CRC cases and 114 UC-no CRC controls. Controls were frequency matched on duration and extent of colitis, age, ethnicity, and gender. All 228 tissue samples were analyzed for five TNF-α promoter polymorphisms (−238[G→A], −308[G→A], −857[C→T], −863[C→A], and −1031[T→C]) using PCR and sequencing. RESULTS: The −308(G→A) SNP was significantly associated with UC-CRC cases at both the allele and genotype level ( P < 0.0001). No other SNPs were significantly associated with UC-CRC. CONCLUSION: We report a novel finding of a strong association between the −308(G→A) SNP and UC-CRC. Complete elucidation of the mechanism of UC-CRC carcinogenesis will require investigation of other genes involved in modulating inflammation, but our results suggest that some UC patients may have additional genetic predispositions toward developing UC-CRC. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00029270
- Volume :
- 103
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- American Journal of Gastroenterology (Springer Nature)
- Publication Type :
- Academic Journal
- Accession number :
- 29383678
- Full Text :
- https://doi.org/10.1111/j.1572-0241.2007.01572.x