Polymorphisms in interleukin 1 beta and interleukin 1 receptor antagonist associated with tumor recurrence in stage II colon cancer
| Autor: | Philipp C. Manegold, Anne M. Schultheis, Hatim Husain, Yan Ning, Georg Lurje, Dongyun Yang, Andrew Hendifar, Heinz-Josef Lenz, Wu Zhang, A. Pohl |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Oncology
Male Vascular Endothelial Growth Factor A medicine.medical_specialty Angiogenesis Colorectal cancer Interleukin-1beta Angiogenesis Pathway Internal medicine Genetics medicine Humans General Pharmacology Toxicology and Pharmaceutics Molecular Biology Genetics (clinical) Neoplasm Staging Polymorphism Genetic business.industry Haplotype Interleukin-8 Cancer Interleukin Middle Aged medicine.disease Vascular Endothelial Growth Factor Receptor-2 Variable number tandem repeat Interleukin 1 Receptor Antagonist Protein Interleukin 1 receptor antagonist Haplotypes Cyclooxygenase 2 Immunology Colonic Neoplasms Molecular Medicine Female Neoplasm Recurrence Local business |
| Zdroj: | Pharmacogenetics and genomics. 19(2) |
| ISSN: | 1744-6872 |
| Popis: | Purpose Identifying molecular markers for tumor recurrence is critical in successfully selecting patients with stage II colon cancer who are more likely to benefit from adjuvant chemotherapy. Interleukin 1 beta (IL1B) and interleukin 1 receptor antagonist (IL1RN) have been shown to play a critical role in the early onset of tumor-associated angiogenesis. In this study, we tested whether eight functionally significant polymorphisms within six genes of the angiogenesis pathway [IL1B, IL1RN, vascular endothelial growth factor A (VEGFA), VEGF receptor 2, interleukin-8, cyclooxygenase-2] will predict the risk of tumor recurrence in stage II colon cancer patients treated with 5-fluorouracil based adjuvant chemotherapy. Experimental design Blood samples were obtained from 109 patients with stage II colon cancer at the University of Southern California medical facilities. DNA was extracted from peripheral blood and the genotypes were analyzed using PCR-restriction fragment length polymorphism protocols. Results Patients harboring the IL1RN/IL1B 1-T-C (IL-1RN variable number tandem repeats (VNTR)/IL1B C+3954T/C-511T) haplotype were at greatest risk of developing tumor recurrence [relative risk (RR): 2.72, 95% confidence interval (CI): 1.22–6.08] (adjusted P=0.015). In addition, IL1B +3954 any T (RR: 2.78, 95% CI: 0.99–7.83) (adjusted P=0.043), IL1RN VNTR (RR: 6.09, 95% CI: 1.11–33.4) (adjusted P=0.038), and VEGFA –634 any C (RR: 2.91, 95% CI: 1.13–7.48) (adjusted P=0.026) were shown to be adverse prognostic markers, in both univariate and multivariable analyses. Conclusion Polymorphisms in IL1B, IL1RN, and VEGFA as well as IL1B/IL1RN haplotype analysis may serve as molecular markers for tumor recurrence in stage II colon cancer, indicating that the analysis of angiogenesis-related gene polymorphisms may help to identify patient subgroups at high risk for tumor recurrence. |
| Databáze: | OpenAIRE |
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