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Association between ulcerative growth andhypoxia inducible factor-1α polymorphisms in colorectal cancer patients
- Source :
- Molecular Carcinogenesis. 45:833-840
- Publication Year :
- 2006
- Publisher :
- Wiley, 2006.
-
Abstract
- 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.
- Subjects :
- Adult
Male
Cancer Research
Colorectal cancer
Molecular Sequence Data
education
Loss of Heterozygosity
colorectal cancer
Biology
Polymerase Chain Reaction
Evolution, Molecular
medicine
Humans
HIF
Amino Acid Sequence
Molecular Biology
Ulcer
polypoid
Aged
DNA Primers
Aged, 80 and over
Polymorphism, Genetic
Base Sequence
Sequence Homology, Amino Acid
hypoxia
Middle Aged
Hypoxia (medical)
Hypoxia-Inducible Factor 1, alpha Subunit
medicine.disease
Immunohistochemistry
Hypoxia-inducible factors
Apoptosis
Immunology
Cancer research
Erythropoiesis
Female
medicine.symptom
Colorectal Neoplasms
Polymorphism, Restriction Fragment Length
ulcerative
Subjects
Details
- ISSN :
- 10982744 and 08991987
- Volume :
- 45
- Database :
- OpenAIRE
- Journal :
- Molecular Carcinogenesis
- Accession number :
- edsair.doi.dedup.....1958db51a96f924a52b9bcf20a2e076f