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HIF-1? -1790G>A polymorphism significantly increases the risk of digestive tract cancer: a meta-analysis.

ABSTRACT: To investigate the association between hypoxia-inducible factor-1? (HIF-1?) polymorphisms (-1772C>T and -1790G>A) and the risk of digestive tract cancer.A total of 13 eligible studies were retrieved from PubMed, EMBASE, and the China National Knowledge Infrastructure database. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the strength of the associations.By pooling the eligible studies, we found that the HIF-1? -1772C>T polymorphism was not associated with the risk of developing digestive tract cancer (dominant comparison, OR: 1.156; 95%CI: 0.839-1.593; P heterogeneity = 0.007), and no significant association was found in the Asian population or the Caucasian population. However, for the -1790G>A polymorphism, carriers of the variant -1790A allele had a significantly increased risk of digestive tract cancer compared with those with the wildtype -1790G allele (dominant comparison, OR: 3.252; 95%CI: 1.661-6.368; P heterogeneity < 0.001). Additionally, this increased risk of digestive cancer was only detected in Asians; there was no significant association in Caucasians.This meta-analysis demonstrates that the HIF-1? -1790G>A polymorphism is associated with a significantly increased risk of digestive tract cancer, while the -1772C>T polymorphism is not.

SUBMITTER: Sun X

PROVIDER: S-EPMC4316108 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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HIF-1α -1790G>A polymorphism significantly increases the risk of digestive tract cancer: a meta-analysis.

Sun Xiao X Liu Ying-Di YD Gao Wei W Shen Shao-Hua SH Li Meng M

World journal of gastroenterology 20150201 5

<h4>Aim</h4>To investigate the association between hypoxia-inducible factor-1α (HIF-1α) polymorphisms (-1772C>T and -1790G>A) and the risk of digestive tract cancer.<h4>Methods</h4>A total of 13 eligible studies were retrieved from PubMed, EMBASE, and the China National Knowledge Infrastructure database. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the strength of the associations.<h4>Results</h4>By pooling the eligible studies, we found that the HIF-1α -1 ...[more]

PMID: 25663785

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Project description:Simple Summary Preoperative Concurrent Chemoradiotherapy (CCRT) is one of the standard treatments for patients with locally advanced rectal cancer. However, the efficacy of CCRT in hyperglycemic rectal cancer patients does not seem to be as expected. Therefore, we used clinical specimens, ectopic hyperglycemia animal models, and rectal cancer cells in a high-glucose environment to confirm how the high-glucose environment causes radiation resistance. The results confirmed that the high-glycemic environment could induce the overexpression of HIF-1α to cause CCRT tolerance in rectal cancer and suggest that combining HIF-1α inhibitors could reverse radioresistance in a high glucose environment. In future, HIF-1α inhibitors might be used as sensitizers to improve the efficacy of hyperglycemic rectal cancer patients receiving CCRT. Abstract Purpose: Preoperative concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced rectal cancer patients. However, the poor therapeutic efficacy of CCRT was found in rectal cancer patients with hyperglycemia. This study investigated how hyperglycemia affects radiochemotherapy resistance in rectal cancer. Methods and Materials: We analyzed the correlation between prognosis indexes with hypoxia-inducible factor-1 alpha (HIF-1α) in rectal cancer patients with preoperative CCRT. In vitro, we investigated the effect of different concentrated glucose of environments on the radiation tolerance of rectal cancers. Further, we analyzed the combined HIF-1α inhibitor with radiation therapy in hyperglycemic rectal cancers. Results: The prognosis indexes of euglycemic or hyperglycemic rectal cancer patients after receiving CCRT treatment were investigated. The hyperglycemic rectal cancer patients (n = 13, glycosylated hemoglobin, HbA1c > 6.5%) had poorer prognosis indexes. In addition, a positive correlation was observed between HIF-1α expression and HbA1c levels (p = 0.046). Therefore, it is very important to clarify the relationship between HIF-1α and poor response in patients with hyperglycemia receiving pre-operative CCRT. Under a high glucose environment, rectal cancer cells express higher levels of glucose transport 1 (GLUT1), O-GlcNAc transferase (OGT), and HIF-1α, suggesting that the high glucose environment might stimulate HIF-1α expression through the GLUT1-OGT-HIF-1α pathway promoting tolerance to Fluorouracil (5-FU) and radiation. In the hyperglycemic rectal cancer animal model, rectal cancer cells confirmed that radiation exposure reduces apoptosis by overexpressing HIF-1α. Combining HIF-1α inhibitors was able to reverse radioresistance in a high glucose environment. Lower HIF-1α levels increased DNA damage in tumors leading to apoptosis. Conclusions: The findings here show that hyperglycemia induces the expression of GLUT1, OGT, and HIF-1α to cause CCRT tolerance in rectal cancer and suggest that combining HIF-1α inhibitors could reverse radioresistance in a high glucose environment. HIF-1α inhibitors may be useful for development as CCRT sensitizers in patients with hyperglycemic rectal cancer.

Dataset Information

HIF-1? -1790G>A polymorphism significantly increases the risk of digestive tract cancer: a meta-analysis.

Publications

HIF-1α -1790G>A polymorphism significantly increases the risk of digestive tract cancer: a meta-analysis.

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