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The C1772T genetic polymorphism in human HIF-1α gene associates with expression of HIF-1α protein in breast cancer

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Author(s)
HYE OK KIMYONG HWA JOJUHIE LEESANG SOOK LEEKYUNG-SIK YOON
Keimyung Author(s)
Lee, Sang Sook
Department
Dept. of Pathology (병리학)
Journal Title
Oncology Reports
Issued Date
2008
Volume
20
Issue
5
Keyword
hypoxia-inducible factor 1αsingle nucleotide polymorphismhypoxia-inducible factor 1α expressionbreast cancer
Abstract
Hypoxia-inducible factor 1 (HIF-1) is an important
genetic component involved in the cellular response to
hypoxia. HIF-1 is also linked to the regulation of tumor
development and growth. In previous studies, the C1772T
(P582S) or the G1790A (A588T) polymorphisms of the
HIF-1α gene have been identified in renal cell carcinoma,
head and neck and esophageal squamous cell carcinomas as
well as colorectal and prostate cancers. In our study, we
investigated whether polymorphisms of the HIF-1α gene may
account for the expression patterns of HIF-1α protein and
impact of clinical progression in breast cancer. We also
examined the impact of prognosis of HIF-1α gene polymorphism
and protein expression in the prediction of
biological behavior. We performed polymerase chain reaction
and direct sequencing to detect polymorphisms in exon 12 of
HIF-1α from 90 breast cancer patients and 102 healthy
controls. The expression of HIF-1α was measured in paraffinembedded
specimens from patients by immunohistochemistry.
We associated its expression with known prognostic factors.
The frequency of the T allele for C1772T in breast cancer
patients and healthy controls was 5.6 vs. 4.4%, whereas, the
frequency of the A allele for G1790A was 1.7 vs. 4.4%.
HIF-1α was overexpressed in 56.7% (51 of 90) of the patients.
Its overexpression associated with the T1772 polymorphic
allele (p=0.04). Elevated levels of HIF-1α protein were found
in cases of breast cancer with lymph node metastasis
(p=0.041), high histological grade (p=0.001) and increased
Ki-67 index (p=0.031). These results suggest the potential
use of C1772T (P582S) polymorphism and expression analysis
in providing a new prognostic factor for unfavorable disease
outcomes and may help for clinical decision-making in the
treatment of breast cancer patients.
Key words: hypoxia-inducible factor 1α, single nucleotide
polymorphism, hypoxia-inducible factor 1α expression, breast cancer
Keimyung Author(s)(Kor)
이상숙
Publisher
School of Medicine
Citation
HYE OK KIM et al. (2008). The C1772T genetic polymorphism in human HIF-1α gene associates with expression of HIF-1α protein in breast cancer. Oncology Reports, 20(5), 1181–1187. doi: 10.3892/or_00000127
Type
Article
ISSN
1021-335X
Source
https://www.spandidos-publications.com/or/20/5/1181
DOI
10.3892/or_00000127
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/33612
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Pathology (병리학)
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