Polymorphisms in the Hypoxia Inducible Factor 1-α and the Impact on the Prognosis of Early Stages of Oral Cancer

Muñoz-Guerra, M.F.; Fernández-Contreras, M.E.; Moreno, A. Capote; Martín, Irene Domínguez; Herráez, Belén; Gamallo, Carlos

doi:10.1245/s10434-009-0503-8

Cited by 56 publications

(51 citation statements)

References 26 publications

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“…Nevertheless, it has been demonstrated that an invasive grade of breast cancer was negatively correlated to ER and PR expression (23,31,32), but positively correlated with HER2 expression (33,34). Similar to MunozGuerra et al (22) and Lanigan et al (24), we found that the absolute increased gene expression level of CLDN16 was significantly negatively correlated with estrogen and progesterone receptor staining density. However, a significantly positive correlation between absolute increased HAPLN3 and human epidermal receptor 2 staining density, and an insignificant association between overall survival and both gene expression levels were found.…”

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confidence: 86%

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Significant elevation of CLDN16 and HAPLN3 gene expression in human breast cancer

et al. 2010

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Abstract. Cancer development involves the destruction of tight junctions, deprivation of cell polarity, and increased cell mobility. Claudin 16 (CLDN16) is a tight junction protein and plays important roles in the maintenance of cell polarity, cellular arrangement, adhesion, paracellular transport, and ionic permeability of various epithelia. A novel link protein, HAPLN3, functions in hyaluronic acid binding and cell adhesion. Both genes are hypothesized to be related to cancer development and metastasis. The purpose of this study was to estimate the roles of the genes CLDN16 and HAPLN3 in breast cancer. A total of 146 samples were collected from breast cancer tissues and their adjacent normal breast tissues. Reverse transcription and real-time polymerase chain reaction were used to estimate gene expression levels. There were significantly increased gene expression of CLDN16 (p<0.0001) and HAPLN3 (p<0.0001) among breast cancer tissues compared with normal tissues, irrespective of clinical pathological parameters. The absolute increased gene expression level of CLDN16 was significantly negatively correlated with estrogen (r=-0.46; p<0.0001) and progesterone receptor (r=-0.384; p=0.001) staining density. However, a significantly positive correlation (r=0.24; p=0.04) between the absolute increased HAPLN3 gene level and human epidermal receptor 2 staining density was found. There was no significant association between overall survival and the two gene expression levels. The gene up-expression of both CLDN16 and HAPLN3 was suggested to be involved in the development of breast cancer and to be a biomarker and target treatment for breast cancer.

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confidence: 86%

“…Recently, it has been hypothesized to play a role in carcinogenesis (17,18,22). For breast epithelial cells, the role of the claudin family on breast cancer is still equivocal.…”

Section: Discussionmentioning

confidence: 99%

Significant elevation of CLDN16 and HAPLN3 gene expression in human breast cancer

et al. 2010

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“…30 Some studies emphasized that G1790A may be a marker of disfavorable prognosis in early stages of oral cancer. 31 We studied rs779805 polymorphism in 5'UTR of VHL gene but no significant differences in genotype and allele frequencies were observed between patients and controls (p> 0.05). Chen et al observed that the rs779805 A>G polymorphism was significantly associated with risk for prostate cancer.…”

Section: Discussionmentioning

confidence: 91%

Colorectal Cancer Risk in Relation to Hypoxia Inducible Factor-1α (Hif-1 α) and Von Hippel-Lindau (Vhl) Gene Polymorphisms.

Demirel¹

2017

UHOD

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Colorectal cancers (CRC) are among the four most frequently seen cancers in humans and are the second leading cause of cancer-related deaths. Hypoxia up regulates multiple genes involved in different steps of metastatic process, including angiogenesis, proliferation, migration, invasion, motility, adhesion and survival. Hypoxia Inducible Factor 1 (HIF-1) is a master regulator protein of cellular hypoxia-response and triggers the expression of above-mentioned metastatic-process genes. Von Hippel Lindau (VHL) is a protein that plays critical role in the response to hypoxia and product of a tumor suppressor gene. We studied three single nucleotide polymorphisms, rs11549465 (1772C > T), rs11549467 (1790G > A) in HIF-1α and rs779805 (5'UTR A > G) in VHL, and assessed their associations with CRC risk, clinicopathologic and demographic features and lifestyle, and tumor stage and grade of CRC patients and/or healthy controls. ARMS-PCR technique for genotyping of rs11549465 C > T and rs11549467 G>A and PCR-RFLP technique for genotyping of rs779805 A>G were used. CT/TT genotypes of HIF-1α 1772C > T polymorphism were found to increase the risk of colorectal cancer in patients (OR= 1.96, 95% CI= 1.02-3.77, p< 0.05). Additionally, it was demonstrated via statistical analyses that higher age, male gender, cancer history in family, co-existing diseases, and exposure to white soil stands to be risk factors of colorectal cancer (p< 0.05). No significant relation was found between patient's TNM stages and distributions of genotype (p> 0.05). The findings from our study demonstrates that, in addition to risk factors for colorectal cancer, scanning CT/TT genotypes of HIF-1α C1772T polymorphism can be advantageous in early-diagnosis of colorectal cancer.Keywords: Colorectal cancer, HIF-1α, VHL, rs11549465, rs11549467 ÖZET Kolorektal Kanser Riski ile Hipoksiyle İndüklenen Faktör-1 Alfa (HIF-1α) ve von Hippel-Lindau (VHL)Kolorektal kanser insanda sık görülen dört kanser türü arasında yer alır ve ölüme götüren kanserler içerisinde ikinci sıradadır. Hipoksi, anjiogenez, proliferasyon, migrasyon, invazyon, adhezyon ve sağkalımı içeren metastatik süreçte rol alan pek çok geni kontrol eder.Birçok kanser türünün gelişmesinde etkili olduğu düşünülen HIF-1α gen proteini hücrenin hipoksiye cevabının anahtar regülatörüdür.VHL proteini tümör baskılayıcı bir genin ürünü olup, hipoksiye cevap yolağında önemli rol alır. Biz bu çalışmada, HIF-1α geninin rs11549465 (1772C > T), rs11549467 (1790G > A) polimorfizmleri ile VHL geninin rs779805 (5'UTR A > G) polimorfizmini ve ayrıca yaş, cinsiyet, ailede kanser öyküsü, sistemik hastalıklar, beyaz toprak maruziyeti, sigara ve alkol tüketimi ile CRC riski arasındaki ilişkiyi araştırdık. Çalışmaya, histolojik olarak teyit edilen CRC tanısı almış 92 hasta ile kontrol grubu olarak 101 birey katıldı. DNA izolasyonu için periferal kan kullanıldı. HIF-1α genindeki rs11549465 C > T ve rs11549467 G>A polimorfizm değişimlerini genotiplemek için ARMS-PZR; VHL rs779805 A > G polimorfizm değişimini genotipleme...

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“…Overall,26 relevant studies involving 6337 cases and 9302 controls were selected in this metaanalysis [21,26,27,29,30,32,[43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62]. The main characteristics of these studies were shown in Table 1.…”

Section: Resultsmentioning

confidence: 99%

“…A number of investigators have studied the possible association between the Hif-1/HIF-1 polymorphisms and cancer risk, but the results have been conflicting [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38]. Thus, the association between the Hif-1/HIF-1 polymorphisms and cancers requires further investigation.…”

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confidence: 99%

Update meta-analysis on 1790G/A polymorphism and cancer risk: Evidence from 26 studies

Liu¹,

Shi²,

Yang³

et al. 2014

neo

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The results from the published studies on the association between hypoxia-inducible factor-1(Hif-1/HIF-1) polymorphisms and cancer risk are conflicting. The common 1790G/A rs11549467) genetic polymorphism has been reported to be functional and may contribute to genetic susceptibility to cancers. However, the association between 1790G/A (rs11549467) and cancer risk remains inconclusive.To better understand the role of 1790G/A (rs11549467) polymorphism in cancer, we conducted this comprehensive metaanalysis encompassing 6337 cases and 9302 controls.Overall, the 1790G/A (rs11549467) genetic polymorphism was associated with higher cancer risk. In the stratified analysis, significant associations were found between the Hif-1/HIF-1 1790G/A polymorphism and lung cancer, pancreatic cancer and oral squamous cell carcinoma. We also observed that the AA genotype might modulate lung cancer (OR=5. (AA vs. GG) and recessive genetic model (AA vs. AG/GG) among Caucasian population. When stratified by study design, significantly elevated susceptibility to cancer was found among hospital-based studies.These findings suggested that the 1790G/A (rs11549467) genetic polymorphism may contribute to the susceptibility of cancers except gynecologic cancer, especially in homozygote comparison and recessive genetic model among Caucasian population, and this SNP was significantly associated with the lung cancer, pancreatic cancer and oral squamous cell carcinoma (OSCC). The phenomenon also indicates that the SNP functions as a recessive mutation needs to be verified or linked with functional studies.

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Polymorphisms in the Hypoxia Inducible Factor 1-α and the Impact on the Prognosis of Early Stages of Oral Cancer

Abstract: Our results suggest that G1790A polymorphism in the HIF-1alpha gene might confer susceptibility to OSCC and could be a marker of disfavorable prognosis at early stages.

Cited by 56 publications

References 26 publications

Significant elevation of CLDN16 and HAPLN3 gene expression in human breast cancer

Significant elevation of CLDN16 and HAPLN3 gene expression in human breast cancer

Colorectal Cancer Risk in Relation to Hypoxia Inducible Factor-1α (Hif-1 α) and Von Hippel-Lindau (Vhl) Gene Polymorphisms.

Update meta-analysis on 1790G/A polymorphism and cancer risk: Evidence from 26 studies

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