Tumor necrosis factor-alpha polymorphisms in ulcerative colitis-associated colorectal cancer.
作者： Megan M. Garrity-Park , Edward V. Loftus , Sandra C. Bryant , William J. Sandborn , Thomas C. Smyrk
DOI: 10.1111/J.1572-0241.2007.01572.X
关键词: Genetic predisposition 、 Immunology 、 Genotype 、 Cancer 、 Single-nucleotide polymorphism 、 SNP 、 Medicine 、 Colitis 、 Allele 、 Carcinogenesis
摘要: OBJECTIVES: Ulcerative colitis (UC) is characterized by chronic recurrent mucosal inflammation. Genetic studies in UC have indicated linkage to chromosome 6 the region of tumor necrosis factor-alpha (TNF-a) gene, a potent proinflammatory cytokine. TNF-α production influenced multiple factors including type immune cell and its level activation. However, several single nucleotide polymorphisms (SNP) promoter TNF-a been correlated with either increased or decreased production, indicating that regulation part genetic. Because patients are at risk for developing colorectal cancer (CRC), we investigated if there was an association between SNPs gene UC-CRC. METHODS: DNA extracted from formalin-fixed, paraffin-embedded tissue 114 UC-CRC cases UC-no CRC controls. Controls were frequency matched on duration extent colitis, age, ethnicity, gender. All 228 samples analyzed five (-238[G→A], -308[G→A], -857[C→T], -863[C→A], -1031[T→C]) using PCR sequencing. RESULTS: The -308(G→A) SNP significantly associated both allele genotype (P < 0.0001). No other CONCLUSION: We report novel finding strong Complete elucidation mechanism carcinogenesis will require investigation genes involved modulating inflammation, but our results suggest some may additional genetic predispositions toward
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