Single nucleotide polymorphism in the hypoxia-inducible factor-1α gene in colorectal carcinoma

Kuwai, Toshio; Kitadai, Yasuhiko; Tanaka, Shinji; Kuroda, Tatsuhiko; Ochiumi, Takehiko; Matsumura, Shunji; Oue, Naohide; Yasui, Wataru; Kaneyasu, Mika; Tanimoto, Keiji; Nishiyama, Masahiko; Chayama, Kazuaki

doi:10.3892/or.12.5.1033

Cited by 34 publications

(46 citation statements)

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“…In this study, the C1772T and G1790A mutation rates in pancreatic cancer were 10% (1/10) and 0%, respectively, for pancreatic cancer and 6.3% (1/16) and 6.3% (1/16), respectively, for gallbladder cancer (all heteromutation-type). These results, together with those of previous reports (2,(8)(9)(10)(11) show a low SNP rate for all cancers, except renal cancer, suggesting the lack of an association between SNPs and carcinogenesis.…”

Section: Discussionsupporting

confidence: 86%

“…However, type 2 diabetes mellitus is a risk factor for pancreatic cancer, which suggests an association between the development of pancreatic cancer and the SNPs of HIF-1α. There have been studies on an association between carcinogenesis and HIF-1α SNPs in cancer in various organs (2,(8)(9)(10)(11). The C1772T and G1790A mutation rates were reported to be 18 and 11%, respectively, in patients with head or neck cancer, and 11 and 8%, respectively, in healthy subjects, with no statistically significant differences between the 2 groups (2).…”

Section: Discussionmentioning

confidence: 99%

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Hypoxia-inducible factor-1α expression and gemcitabine chemotherapy for pancreatic cancer

et al. 2011

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Abstract. The normal pancreas has an abundant blood flow, in contrast to pancreatic cancer, which is a hypovascular tumor. During hypoxia under a hypovascular environment, the transcription factor hypoxia-inducible factor-1α (HIF-1α) is activated. High HIF-1α expression reduces sensitivity to gemcitabine (GEM) which is used as a treatment for pancreatic cancer. The objective of this study was to clarify HIF-1α expression in pancreatic cancer and the association of its effects to GEM treatment. We used the human pancreatic ductal carcinoma cell lines AsPC-1 and BxPC-3 to evaluate cell proliferation, HIF-1α protein expression and sensitivity to GEM in a hypoxic environment of 1% O 2 in 48 pancreatic cancer patients who received adjuvant GEM treatment after pancreatectomy. We divided the patients according to HIF-1α expression and the presence of single nucleotide polymorphisms, and we based our evaluation on the adverse events associated with GEM chemotherapy and patient outcome. The hypoxic environment promoted cell proliferation, induced HIF-1α expression and increased GEM resistance, especially in AsPC-1 cells, which included a mutant homozygote for HIF-1α(C1772T). There were no significant differences between the HIF-1α(-) and HIF-1α(+) groups in either adverse events or patient outcomes. HIF-1α enhanced neo-microvascularity in a hypoxic environment and increased drug resistance. The period until recurrence was shorter in the patients with a strong HIF-1α expression, than that in those with a weak HIF-1α expression.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Hypoxia-inducible factor-1α expression and gemcitabine chemotherapy for pancreatic cancer

et al. 2011

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“…However, the exact mechanism of these polymorphisms in the development of digestive cancer is not clearly understood (Huang et al, 2012). Recent evidence has suggested that HIF-1α gene polymorphisms may be associated with increased digestive cancer risk (Ling et al, 2005;Fransen et al, 2006;Li et al, 2009;Hsiao et al, 2010;Kang et al, 2011;Wang et al, 2011); however, individually published results are inconclusive (Kuwai et al, 2004;Knechtel et al, 2010). Therefore, we attempt to perform a meta-analysis of all eligible case-control studies to provide insights into these associations, which may promote our understanding of the exact role of the HIF-1α gene in the development of carcinogenesis in the digestive organs.…”

Section: Introductionmentioning

confidence: 62%

“…Two common functional polymorphisms, C1772T (rs11549465 C>T) and G1790A (rs11549467 G>A), in the human HIF-1α gene that cause amino acid substitutions within the oxygen-dependent degradation domain may result in the overexpression of this protein and subsequent changes in the expression of downstream target genes, thus contributing to cancer development and progression (Chau et al, 2005). Several previous studies have suggested that HIF-1α C1772T and G1790A polymorphisms may play important roles in the risk of digestive cancer (Ling et al, 2005;Fransen et al, 2006;Li et al, 2009;Hsiao et al, 2010;Kang et al, 2011;Wang et al, 2011), while other studies found no convincing evidence of these polymorphisms in increasing susceptibility to digestive cancer (Kuwai et al, 2004;Knechtel et al, 2010). This controversy could be explained with several reasons such as the differences in study designs, sample size, ethnicity, source of controls, cancer types, and genotype methods.…”

Section: Discussionmentioning

confidence: 94%

“…In accordance with the inclusion criteria, 8 case-control studies (Kuwai et al, 2004;Ling et al, 2005;Fransen et al, 2006;Li et al, 2009;Hsiao et al, 2010;Knechtel et al, 2010;Kang et al, 2011;Wang et al, 2011) were included in this meta-analysis and 91 articles were excluded. The flow chart of the study selection process is shown in Figure 1.…”

Section: Baseline Characteristics Of Included Studiesmentioning

confidence: 99%

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Common polymorphisms in the HIF-1αgene confer susceptibility to digestive cancer: a meta-analysis

Zou

Liu

et al. 2014

Genet. Mol. Res.

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ABSTRACT. Recent evidence suggests that common functional polymorphisms in the hypoxia inducible factor-1α (HIF-1α) gene may play an important role in the development and progression of digestive cancer, but individually published results are inconclusive. Our metaanalysis is aimed to derive a more precise estimation of the relationships between HIF-1α gene polymorphisms and digestive cancer risk. An extensive literature search for relevant studies was conducted on Pubmed, Embase, Web of Science, Cochrane Library, and CBM databases from their inception through May 1, 2013. This meta-analysis was performed using the STATA 12.0 software. The crude odds ratios (OR) with 95% confidence interval (CI) were calculated. Eight case-control studies were included with a total of 1276 digestive cancer patients and 3392 healthy controls. Our meta-analysis revealed that the A variant of HIF-1α G1790A polymorphism might be associated with increased risk of colorectal, esophageal, gastric, and liver cancers, especially among Asian populations. However, no statistically significant associations were found between HIF-1α C1772T polymorphism and susceptibility to digestive cancer. No publication bias was detected in this metaanalysis. The current meta-analysis suggests that the HIF-1α G1790A polymorphism may increase the risk of colorectal, esophageal, gastric, and liver cancers, especially among Asian populations.

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HIF1A gene polymorphisms and human diseases: Graphical review of 97 association studies

Gladek

Ferdin

Horvat

et al. 2017

Genes Chromosomes & Cancer

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Hypoxia-inducible factors (HIFs) belong to a family of transcription factors (TF) responsive to a low O2 availability, which is often a characteristic feature of solid tumors. The alpha subunit of the HIF heterodimer is O2-sensitive, and once stabilized in hypoxia, it functions as a master regulator of various genes involved in hypoxia pathway. Changes in the HIF1A (hypoxia inducible factor 1, alpha subunit) nucleotide sequence or expression has been shown to be associated with development of several diseases. Due to increasing research interest in HIF1A gene a review of association studies was needed. We here reviewed published data on single nucleotide polymorphisms (SNPs) in HIF1A in various diseases; in total, 34 SNPs were tested for an association with 49 phenotypes, and the results were visualized using the Cytoscape software. Among all collected polymorphisms 16 SNPs showed significant associations with 40 different phenotypes, including six SNPs associated with 14 cancer types. Missense SNPs (rs11549465 and rs11549467) within the oxygen-dependent degradation domain were most frequently studied. The study provides a comprehensive tool for researchers working in this area and may contribute to more accurate disease diagnosis and identification of therapeutic targets.

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Single nucleotide polymorphism in the hypoxia-inducible factor-1α gene in colorectal carcinoma

Cited by 34 publications

References 0 publications

Hypoxia-inducible factor-1α expression and gemcitabine chemotherapy for pancreatic cancer

Hypoxia-inducible factor-1α expression and gemcitabine chemotherapy for pancreatic cancer

Common polymorphisms in the HIF-1αgene confer susceptibility to digestive cancer: a meta-analysis

HIF1A gene polymorphisms and human diseases: Graphical review of 97 association studies

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