Heme Oxygenase-1 Gene Promoter Polymorphism is Associated with Risk of Gastric Adenocarcinoma and Lymphovascular Tumor Invasion

Lo, Su Shun; Lin, Shu Chun; Wu, Chew Wun; Chen, Jen-Hao; Yeh, Wen I.; Chung, Ming Yi; Lui, Wing Yiu

doi:10.1245/s10434-006-9290-7

Cited by 53 publications

(41 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has also demonstrated that SS genotype could cause increasing of metastatic activity risk of gastric cancer. Against our results, Lo and coworkers demonstrated that L allele is associated with risk of gastric cancer [19]. Also, studies of Dicken et al [4] on cardiovascular patients, Yamada et al [34] on emphysema, Wu et al [33] on carotid atherosclerosis, Schillinger et al [25]) on abdominal aortic aneurysm, and Chang et al [2] on squamous cell carcinoma showed that L allele has an association with those diseases.…”

Section: Discussionsupporting

confidence: 61%

Association between GT-repeat polymorphism at heme oxygenase-1 gene promoter and gastric cancer and metastasis

Motovali-Bashi

Hamidy

2015

Tumor Biol.

View full text Add to dashboard Cite

HO-1 gene encodes heme oxygenase-1 enzyme that catalyzes the oxidation of heme to carbon monoxide (CO). It has also been suggested that cells could be protected by the enzyme against stress. A (GT) n dinucleotide repeat at HO-1 promoter is a polymorphic region and modulates gene transcription and associated with some of diseases. In this study, length of polymorphism GT tandem repeat has been determined and classified into two alleles short (≤28) and long (≥29). In present study, association between GT-repeat polymorphism at heme oxygenase-1 gene promoter and increased risk of gastric cancer and metastasis was investigated. Blood samples from 100 control individuals and 60 gastric cancer cases had taken. Genotypic frequencies of (GT) n repeat for samples were determined using PCR technique and polyacrylamide PAGE electrophoresis. At final, higher frequency alleles were sequenced. Our results show that S-allele is significantly higher in cases in comparison with control groups (p = 0/000, odds ratio (OR) = 4/154). It has been shown that individuals with S/S and S/L genotypes are at high risk of having gastric cancer (p = 0/000, OR = 3/789). Statistic data show association between SS genotype and risk of gastric cancer metastasis (p = 0.017, OR = 3.889). But, there is no significant association between clinicopathological characteristics of the patients and risk of gastric cancer metastasis (p > 0.05). Significant association was found between short allele (SS + SL genotypes) and risk of gastric cancer, and also strong association was found between SS genotype and risk of gastric cancer metastasis.

show abstract

Section: Discussionsupporting

confidence: 61%

Association between GT-repeat polymorphism at heme oxygenase-1 gene promoter and gastric cancer and metastasis

Motovali-Bashi

Hamidy

2015

Tumor Biol.

View full text Add to dashboard Cite

show abstract

“…An association with functional polymorphisms of the HO-1 gene and clinical outcome parameters has also been found in other pathological conditions, such as pulmonary emphysema, certain cardiovascular diseases and malignancies (14,19,(30)(31)(32)(33)(34)(35). With respect to transplantation, two groups have previously reported an association between HO-1 polymorphism in the donor and outcome after kidney transplantation (21,22).…”

Section: Discussionmentioning

confidence: 89%

Heme Oxygenase-1 Genotype of the Donor Is Associated With Graft Survival After Liver Transplantation

Buis

Steege

Visser

et al. 2008

American Journal of Transplantation

View full text Add to dashboard Cite

Heme oxygenase-1 (HO-1) has been suggested as a cytoprotective gene during liver transplantation. Inducibility of HO-1 is modulated by a (GT) n polymorphism and a single nucleotide polymorphism (SNP) A(-413)T in the promoter. Both a short (GT) n allele and the A-allele have been associated with increased HO-1 promoter activity. In 308 liver transplantations, we assessed donor HO-1 genotype and correlated this with outcome variables. For (GT) n genotype, livers were divided into two classes: short alleles (<25 repeats; class S) and long alleles (≥25 repeats; class L). In a subset, hepatic messenger ribonucleic acid (mRNA) expression was correlated with genotypes. Graft survival at 1 year was significantly better for A-allele genotype compared to TT-genotype (84% vs. 63%, p = 0.004). Graft loss due to primary dysfunction (PDF) occurred more frequently in TT-genotype compared to A-receivers (p = 0.03). Recipients of a liver with TT-genotype had significantly higher serum transaminases after transplantation and hepatic HO-1 mRNA levels were significantly lower compared to the A-allele livers (p = 0.03). No differences were found for any outcome variable between class S and LL-variant of the (GT) n polymorphism. Haplotype analysis confirmed dominance of the A(-413)T SNP over the (GT) n polymorphism. In conclusion, HO-1 genotype is associated with outcome after liver transplantation. These findings suggest that HO-1 mediates graft survival after liver transplantation.

show abstract

“…A GT length-promoter polymorphism for HO-1 has been described that controls the level of HO-1 expression and has been shown to be highly correlative with severity of disease, including cancer (27). Individuals with a long (GT)n repeat, which is associated with low expression levels of HO-1, showed a higher frequency of gastric or lung adenocarcinoma (28) and oral squamous cancer (29) than individuals with short GT repeats and higher HO-1 expression. Additionally, application of CO via a CO-releasing molecule provided a significant inhibition in photocarcinogenesis in mice (30).…”

Section: Discussionmentioning

confidence: 99%

Heme oxygenase-1 and carbon monoxide modulate DNA repair through ataxia-telangiectasia mutated (ATM) protein

Otterbein

Hedblom²,

Harris³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Stability and repair of DNA is of principal importance in cell survival. Heme oxygenase-1 (HO-1; Hmox1) is critical in maintaining cellular homeostasis, in large part through its ability to generate CO, but neither molecule has been studied in the setting of DNA damage. Naïve Hmox1 −/− mice exhibit excessive tissue levels of γ-histone H2A, whereas administration of genotoxic stressors or irradiation in HO-1-deficient cells resulted in loss of ataxia-telangiectasia mutated/ataxia telangiectasia and Rad3-related protein and breast cancer 1, early onset induction with dysfunctional γ-H2AX foci and marked elevations in DNA damage. HO-1 induction or exposure to CO induced homologous recombination-mediated DNA repair through ataxia-telangiectasia mutated/ataxia telangiectasia and Rad3-related protein. In vivo, exposure of mice to CO followed by genotoxin (Adriamycin) or radiation-induced injury led to diminished tissue DNA damage and improved survival. We characterize a joint role for HO-1 and the gasotransmitter CO for appropriate DNA repair and provide a mechanism for their potent cytoprotective effects in various pathologies.chemotherapy | heme degradation | gas biology | cytoprotection E fficient DNA damage repair and checkpoint mechanisms are critical components of normal cellular function to maintain the integrity of genomic DNA (reviewed in refs. 1 and 2). DNA lesions are induced in response to UV or ionizing radiation as well as many chemicals including endogenous metabolites and reactive oxygen species (ROS) (1). DNA repair pathways include repair of damaged bases or single-strand DNA breaks (base excision repair) and repair of double-strand DNA breaks (DSB) including homologous recombination (HR) and nonhomologous end-joining (NHEJ). The cellular response to DNA DSBs occurs via an integrated sensing and signaling network that maintains and restores genomic stability (3). DSBs are detected initially by damage sensors that trigger the activation of transducing kinases. These transducers amplify the damage signal and relay it to effector proteins, which in turn regulate cell-cycle progression, DNA repair, and apoptosis (4). DSBs are recognized by the Mre11-Rad50-Nbs1 (MRN) mediator complex which recruits ataxia telangiectasia-mutated (ATM) to the broken DNA (4). Cells also are faced with detection of replication blocks, which is mediated by an ssDNA-replication protein A complex recruiting the kinases ataxia-telangiectasia and rad3-related (ATR) and Rad17 (5). Both ATR and ATM can phosphorylate multiple target proteins [p53 binding protein 1, breast cancer 1, early onset (Brca1), checkpoint kinase 1, checkpoint kinase 2 (Chk2), and the MRN complex, among others; more than 700 proteins have been identified so far] that mediate the downstream signaling. Further, in response to DNA damage or structural alterations of chromatin, histone H2A is phosphorylated on Ser139 by ATM, ATR, or by DNA-dependent protein kinases. This phosphorylation allows recruitment of additional DNA damage-responsive proteins and the format...

show abstract

Heme Oxygenase-1 Gene Promoter Polymorphism is Associated with Risk of Gastric Adenocarcinoma and Lymphovascular Tumor Invasion

Abstract: These findings suggest that the long (GT)n repeat of HO-1 gene promoter was associated with a higher frequency of gastric adenocarcinoma, and the medium (GT)n repeat might possess protective effect against gastric adenocarcinoma with a lower frequency of lymphovascular invasion in tumors.

Cited by 53 publications

References 41 publications

Association between GT-repeat polymorphism at heme oxygenase-1 gene promoter and gastric cancer and metastasis

Association between GT-repeat polymorphism at heme oxygenase-1 gene promoter and gastric cancer and metastasis

Heme Oxygenase-1 Genotype of the Donor Is Associated With Graft Survival After Liver Transplantation

Heme oxygenase-1 and carbon monoxide modulate DNA repair through ataxia-telangiectasia mutated (ATM) protein

Contact Info

Product

Resources

About