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Association between...
Association between ulcerative growth and hypoxia inducible factor-1alpha polymorphisms in colorectal cancer patients
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- Fransén, Karin, 1973- (författare)
- Division of Cell Biology, Department of Biomedicine and Surgery, Faculty of Health Sciences, Linköping, Sweden
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- Fenech, Matthew (författare)
- Division of Cell Biology, Department of Biomedicine and Surgery, Faculty of Health Sciences, Linköping, Sweden
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- Fredrikson, Mats (författare)
- Division of Occupational and Environmental Medicine, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, University Hospital, Linköping, Sweden
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- Dabrosin, Charlotta (författare)
- Division of Gynecologic Oncology, University Hospital, Faculty of Health Sciences, Linköping, Sweden
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- Söderkvist, Peter (författare)
- Division of Cell Biology, Department of Biomedicine and Surgery, Faculty of Health Sciences, Linköping, Sweden
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(creator_code:org_t)
- 2006
- 2006
- Engelska.
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Ingår i: Molecular Carcinogenesis. - : John Wiley & Sons. - 0899-1987 .- 1098-2744. ; 45:11, s. 833-840
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- The hypoxia inducible factor-1alpha (HIF-1alpha) has been found to be involved in several different physiological mechanisms, such as blood-vessel formation, apoptosis, and erythropoiesis. HIF-1alpha is hydroxylated at normoxia and rapidly degraded via the von Hippel-Lindau (VHL)/ubiquitin-proteasome degradation system to prevent angiogenesis. In a previous study, the C1772T (P582S) and the G1790A (A588T) polymorphisms were identified in the human HIF-1alpha gene, which was shown to have a higher transactivating capability in vitro compared to the wild type allele. However, the role for these polymorphisms in vivo is still unclear. In the present investigation, we have therefore studied the role of the two polymorphic variants in the development of colorectal cancer (CRC) with PCR/RFLP (restriction fragment length polymorphism), single strand conformation analysis (SSCA), and immunohistochemistry (IHC). A significant higher-risk was identified between patients heterozygous for the C1772T polymorphism and the more severe ulcerative growth pattern compared to homozygous C1772C wild type tumors (RR = 5.2; 95% CI 1.26-21.6; P = 0.006). This was also verified on the allelic level (RR = 6.5; 95% CI 1.58-26.8; P = 0.001). In addition, patients carrying one or more polymorphic alleles in either the HIF-1alpha C1772T or the G1790A polymorphisms display significant higher risk for the development of ulcerative CRCs (RR = 4.17; 95% CI = 1.33-13.08; P = 0.004). These results suggest that the HIF-1alpha polymorpisms are an important factor for development of a subset of ulcerative intestinal tumors. Future screening of the polymorphic HIF-1alpha allele may therefore be of importance in the selection of treatment strategies of CRC.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- HIF
- hypoxia
- ulcerative
- polypoid
- colorectal cancer
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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