Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Bohanes, P; Yang, D; Loupakis, F; LaBonte, MJ; Gerger, A; Ning, Y; Lenz, C; Lenz, F; Wakatsuki, T; Zhang, W; Benhaim, L; El-Khoueiry, A; El-Khoueiry, R; Lenz, HJ.
Integrin genetic variants and stage-specific tumor recurrence in patients with stage II and III colon cancer.
Pharmacogenomics J. 2015; 15(3):226-234
Doi: 10.1038/tpj.2014.66
Web of Science
PubMed
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- Co-authors Med Uni Graz
- Gerger Armin
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- Abstract:
- Integrins (ITGs) are key elements in cancer biology, regulating tumor growth, angiogenesis and lymphangiogenesis through interactions of the tumor cells with the microenvironment. Moving from the hypothesis that ITGs could have different effects in stage II and III colon cancer, we tested whether a comprehensive panel of germline single-nucleotide polymorphisms (SNPs) in ITG genes could predict stage-specific time to tumor recurrence (TTR). A total of 234 patients treated with 5-fluorouracil-based chemotherapy at the University of Southern California were included in this study. Whole-blood samples were analyzed for germline SNPs in ITG genes using PCR-restriction fragment length polymorphism or direct DNA sequencing. In the multivariable analysis, stage II colon cancer patients with at least one G allele for ITGB3 rs4642 had higher risk of recurrence (hazard ratio (HR)=4.027, 95% confidence interval (95% CI) 1.556-10.421, P=0.004). This association was also significant in the combined stage II-III cohort (HR=1.975, 95% CI 1.194-3.269, P=0.008). The predominant role of ITGB3 rs4642 in stage II diseases was confirmed using recursive partitioning, showing that ITGB3 rs4642 was the most important factor in stage II diseases. In contrast, in stage III diseases the combined analysis of ITGB1 rs2298141 and ITGA4 rs7562325 allowed to identify three distinct prognostic subgroups (P=0.009). The interaction between stage and the combined ITGB1 rs2298141 and ITGA4 rs7562325 on TTR was significant (P=0.025). This study identifies germline polymorphisms in ITG genes as independent stage-specific prognostic markers for stage II and III colon cancer. These data may help to select subgroups of patients who may benefit from ITG-targeted treatments.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Aged -
- Aged, 80 and over -
- Alleles -
- Antimetabolites, Antineoplastic - therapeutic use
- Colonic Neoplasms - drug therapy
- Colonic Neoplasms - genetics
- Colonic Neoplasms - pathology
- Female -
- Fluorouracil - therapeutic use
- Genotype -
- Humans -
- Integrins - genetics
- Male -
- Middle Aged -
- Neoplasm Recurrence, Local - genetics
- Neoplasm Recurrence, Local - pathology
- Neoplasm Staging - methods
- Polymorphism, Single Nucleotide - genetics
- Prognosis -
- Young Adult -