Quercetin: Its Antioxidant Mechanism, Antibacterial Properties and Potential Application in Prevention and Control of Toxipathy.

Quercetin, as a flavonol compound found in plants, has a variety of biological activities. It is widely present in nature and the human diet, with powerful oxidative properties and biological activities. In this review, the antioxidant mechanism and broad-spectrum antibacterial properties of quercetin are revealed; the intervention effects of quercetin on pesticide poisoning and the pathway of action are investigated; the toxic effects of main mycotoxins on the collection and the detoxification process of quercetin are summarized; whether it is able to reduce the toxicity of mycotoxins is proved; and the harmful effects of heavy metal poisoning on the collection, the prevention, and control of quercetin are evaluated. This review is expected to enrich the understanding of the properties of quercetin and promote its better application in clinical practice.

Can auditory brain stem response accurately reflect the cochlear function?

Auditory brain stem response (ABR) and compound action potential (CAP) recordings have been used in animal research to determine hearing sensitivity. Because of the relative ease of testing, the ABR test has been more commonly used in assessing cochlear lesions than the CAP test. The purpose of this experiment is to examine the difference between these two methods in monitoring the dynamic changes in auditory function after cochlear damage and in detecting asymmetric hearing loss due to unilateral cochlear damage. ABR and CAP were measured in two models of cochlear damage: acoustic trauma induced by exposure to a narrowband noise centered at 4 kHz (2,800-5,600 Hz) at 105 dB sound pressure level for 5 h in chinchillas and unilateral cochlear damage induced by surgical destruction of one cochlea in guinea pigs. Cochlear hair cells were quantified after completing the evoked potential testing. In the noise-damaged model, we found different recovery patterns between ABR and CAP. At 1 day after noise exposure, the ABR and CAP assessment revealed a similar level of threshold shifts. However, at 30 days after noise exposure, ABR thresholds displayed an average of 20-dB recovery, whereas CAP thresholds showed no recovery. Notably, the CAP threshold signifies the actual condition of sensory cell pathogenesis in the cochlea because sensory cell death is known to be irreversible in mammals. After unilateral cochlear damage, we found that both CAP and ABR were affected by cross-hearing when testing the damaged ear with the testing stimuli delivered directly into the canal of the damaged ear. When cross-hearing occurred, ABR testing was not able to reveal the presence of cross-hearing because the ABR waveform generated by cross-stimulation was indistinguishable from that generated by the test ear (damaged ear), should the test ear be intact. However, CAP testing can provide a warning sign, since the typical CAP waveform became an ABR-like waveform when cross-hearing occurred. Our study demonstrates two advantages of the CAP test over the ABR test in assessing cochlear lesions: contributing evidence for the occurrence of cross-hearing when subjects have asymmetric hearing loss and providing a better assessment of the progression of cochlear pathogenesis.NEW & NOTEWORTHY Auditory brain stem response (ABR) is more commonly used to evaluate cochlear lesions than cochlear compound action potential (CAP). In a noise-induced cochlear damage model, we found that the reduced CAP and enhanced ABR caused the threshold difference. In a unilateral cochlear destruction model, a shadow curve of the ABR from the contralateral healthy ear masked the hearing loss in the destroyed ear.

Clinical analysis of Kimura's disease in 24 cases from China.

BACKGROUND: We reviewed details of Chinese Kimura's disease (KD) cases. A full clinical analysis was subsequently performed to improve the accuracy of clinical diagnosis and treatment of KD. METHODS: A total of 24 patients with pathologically confirmed KD treated between March 2008 and March 2018 were reviewed retrospectively for clinical and histopathological analysis. RESULTS: In the 24 KD cases, 20 were male and 4 were female with the age of onset ranging from 5 to 65 years. Lesion diameter ranged from 0.6 cm to 7 cm with unilateral involvement being more popular (79%). Imaging examination had a high detection rate for KD involving the parotid gland and subcutaneous but had low specificity. Microscopic analysis indicated that KD mainly involved subcutaneous soft tissue and lymph nodes. The prominent feature of lymphoid tissue was germinal center hyperplasia surrounded by several lobules associated with hyperplastic vascular structures. Out of the 24 patients, 11 experienced recurrence of disease after treatment (surgical resection: 46.2%, surgical resection followed by oral corticosteroids: 71.4% and surgical resection combined with radiotherapy: 0%). CONCLUSIONS: Our analysis revealed clinical, imaging, and histological characteristics of KD. A better understanding of the disease will help clinicians reduce misdiagnosis and improve the diagnostic rate upon patient first clinical visit.

Long non-coding RNA LINC01225 promotes proliferation, invasion and migration of gastric cancer via Wnt/ß-catenin signalling pathway.

Emerging evidence has classified the aberrant expression of long non-coding RNAs (lncRNAs) as a basic signature of various malignancies including gastric cancer (GC). LINC01225 has been shown to act as a hepatocellular carcinoma-related gene, with its expression pattern and biological function not clarified in GC. Here, we verified that LINC01225 was up-regulated in tumour tissues and plasma of GC. Analysis with clinicopathological information suggested that up-regulation of LINC01225 was associated with advanced disease and poorer overall survival. Receiver operating characteristic (ROC) analysis showed that plasma LINC01225 had a moderate accuracy for diagnosis of GC. In addition, knockdown of LINC01225 led to retardation of cell proliferation, invasion and migration, and overexpression of LINC01225 showed the opposite effects. Mechanistic investigations showed that LINC01225 silencing inhibited epithelial-mesenchymal transition (EMT) process and attenuated Wnt/ß-catenin signalling of GC. Furthermore, ectopic expression of Wnt1 or suppression of GSK-3ß abolished the si-LINC01225-mediated suppression against EMT, thereby promoting cell proliferation, invasion and migration of GC. In conclusion, LINC01225 promotes the progression of GC through Wnt/ß-catenin signalling pathway, and it may serve as a potential target or strategy for diagnosis or treatment of GC.

MicroRNA-140-5p inhibits the progression of colorectal cancer by targeting VEGFA.

BACKGROUND: microRNAs (miRNAs) are small non-coding RNAs and have been shown to play a crucial role in the colorectal cancer (CRC) tumorigenesis and progression. The aim of this study was to investigate the clinical significance and prognostic value of miR-140-5p in CRC. The exact functions and the underlying molecular mechanisms of miR-140-5p in CRC was further determined. METHODS: miR-140-5p expression was detected in CRC samples, their adjacent nontumor tissues as well as CRC cell lines by RT-qPCR. Cell proliferation was detected using CCK-8, and cell invasion and migration were evaluated using Transwell assay. The direct regulation of VEGFA by miR-140-5p was identified using luciferase reporter assay. RESULTS: miR-140-5p was significantly dowregulated in CRC tissues and cell lines. Downregulation of miR-140-5p was significantly correlated with advanced CRC stage and poorer overall survival. Both gain-of-function and loss of function studies demonstrated that miR-140-5p acted as a tumor suppressor by inhibiting cell proliferation, migration and invasion. Integrated analysis identified VEGFA as a direct and functional target gene of miR-140-5p. Silencing VEGFA by small interfering RNA (siRNA) resembled the phenotype resulting from ectopic miR-140-5p expression, while overexpression of VEGFA attenuated the effect of miR-140-5p on CRC cells. CONCLUSIONS: Our results suggested a tumor suppressive role of miR-140-5p in CRC tumorigenesis and progression by targeting VEGFA.

Clinicopathological significance of SLP-2 overexpression in human gallbladder cancer.

Several studies have indicated that overexpression of stomatin-like protein 2 (SLP-2) has been identified in several types of cancer. However, its role and clinical relevance in gallbladder cancer (GBC) is unknown. The purpose of this study was to reveal the prognostic significance of SLP-2 in GBC. The SLP-2 expression was examined at mRNA and protein levels by real-time quantitative polymerase chain reaction (qRT-PCR), and immunohistochemistry in GBC tissues and adjacent noncancerous tissues. Statistical analyses were applied to test the associations between SLP-2 expression, clinicopathologic factors, and prognosis. Immunohistochemistry and qRT-PCR showed that the protein and mRNA expression levels of SLP-2 were both significantly higher in GBC tissues than in adjacent noncancerous tissues. In addition, immunohistochemistry analysis showed that SLP-2 expression was significantly correlated with histological grade (P <0.001), pathologic T stage (P = 0.019), clinical stage (P = 0.001), and lymph node metastasis (P = 0.026). The Kaplan-Meier survival curves indicated that patients with high expression of SLP-2 had shorter overall survival than those with low expression (P <0.001). Meanwhile, the Cox multivariate analysis indicated that high expressions of SLP-2 were an independent prognostic factor for patients with GBC. These data showed that SLP-2 may play an important role in human GBC tumorigenesis, and SLP-2 might serve as a novel prognostic marker in human GBC.

Extrasynaptic distribution of NMDA receptors in cochlear inner hair cell afferent signaling complex.

OBJECTIVE: The distribution and role of NMDA receptors is unclear in the afferent signaling complex of the cochlea. The present study aimed to examine the distribution of NMDA receptors in cochlear afferent signaling complex of the adult mouse, and their relationship with ribbon synapses of inner hair cells (IHCs) and GABAergic efferent terminals of the lateral olivocochlear (LOC). METHODS: Immunofluorescence staining in combination with confocal microscopy was used to investigate the distribution of glutamatergic NMDA and AMPA receptors in afferent terminals of SGNs, and their relationship with ribbon synapses of IHCs and GABAergic efferent terminals of LOC. RESULTS: Terminals with AMPA receptors along with Ribbons of IHC formed afferent synapses in the basal pole of IHCs, and those with NMDA receptors were mainly distributed longitudinally in the IHCs nuclei region. Significant difference was found in the distribution of NMDA and AMPA receptors in IHC afferent signaling complex (P<0.05). Some GABAergic terminals colocalized with NMDA receptors at the IHC nucleus region (P>0.05). CONCLUSION: There is significant difference in the distribution of NMDA and AMPA receptors in cochlear afferent signaling complex. NMDA receptors are present in the extra-synaptic region of ribbon synapses of IHCs, and they are related to GABA efferent terminals of the afferent signaling complex.

Store-Operated Ca2+ Channels Contribute to the Generation of Ca2+ Waves in Interdental Cells in the Cochleae.

Cochlear calcium (Ca2+) waves are vital regulators of the cochlear development and establishment of hearing function. Inner supporting cells are believed to be the main region generating Ca2+ waves that work as internal stimuli to coordinate the development of hair cells and the mapping of neurons in the cochlea. However, Ca2+ waves in interdental cells (IDCs) that connect to inner supporting cells and spiral ganglion neurons are rarely observed and poorly understood. Herein, we reported the mechanism of IDC Ca2+ wave formation and propagation by developing a single-cell Ca2+ excitation technology, which can easily be accomplished using a two-photon microscope for simultaneous microscopy and femtosecond laser Ca2+ excitation in any target individual cell in fresh cochlear tissues. We demonstrated that the store-operated Ca2+ channels in IDCs are responsible for Ca2+ wave formation in these cells. The specific architecture of the IDCs determines the propagation of Ca2+ waves. Our results provide the mechanism of Ca2+ formation in IDCs and a controllable, precise, and noninvasive technology to excite local Ca2+ waves in the cochlea, with good potential for research on cochlear Ca2+ and hearing functions.

Influence of Orai1 intervention on mouse airway epithelium reactions in vivo and in vitro.

BACKGROUND: Orai1 is crucial for store-operated Ca2(+) entry and Ca2(+) release-activated Ca2(+) channel activities. However, little is known about its function in allergic diseases. OBJECTIVE: To assess the influence of Orai1 intervention on mouse airway epithelium reactions in vivo and in vitro. METHODS: We used immunohistochemical staining, enzyme-linked immunosorbent assay, and real-time reverse transcription-polymerase chain reaction to evaluate Orai1 expression in nasal and tracheal mucosa epithelium of nonsensitized, control, and 2-aminoethoxydiphenyl borate (2-APB)-treated groups in vivo and in vitro. In addition, we analyzed concentrations of interleukin 1ß, interleukin 6, macrophage inflammatory protein 2, and tumor necrosis factor α in nasal lavage fluid, bronchoalveolar lavage fluid, and culture supernatant and their messenger RNAs in nasal and tracheal mucosa and cultured nasal and tracheal epithelium. RESULTS: Administration of 2-APB into the nostrils suppressed Orai1 expression in nasal and tracheal mucosa of treated mice compared with that in control mice and restrained the mediators in nasal lavage fluid, bronchoalveolar lavage fluid, and airway mucosa of treated groups compared with those in control groups. Similarly, the 2-APB intervention also alleviated Orai1 and the production of the mediators in culture supernatant and cultured airway epithelium under allergic conditions. CONCLUSIONS: Our results indicate that 2-APB could effectively ameliorate reactions of upper and lower airway epithelial cells in mice in allergic states in vivo and in vitro.

Removal of lead (Pb+2) from contaminated water using a novel MoO3-biochar composite: Performance and mechanism.

Removal of toxic chemicals from the environment using novel adsorbents is of great concern. In this study, a novel composite of molybdenum trioxide (MoO3)-engineered biochar (MoO3-BC) was derived from corn straw and synthesized for the removal of Pb(II) from water. The pyrolysis temperature of 600 °C was suitable for the thermal self-assembly of MoO3-BC. Although MoO3-BC had lower SBET (59.3 m2/g) than the pristine BC (157.8 m2/g), it had a stronger adsorption affinity to Pb(II). The Pb(II) removal capacity of MoO3-BC was 229.87 mg/g at pH 4.0, and the adsorptive removal of Pb(II) was fit using a pseudo-second-order model and the Langmuir model. High temperature favored the removal of Pb(II) by MoO3-BC; However, the removal of Pb(II) was inhibited with increasing the ion strength. The MoO3-BC revealed an acceptable stability and reusability, since the removal efficiency of Pb(II) remained above 80.7%, even after 8 cycles. The MoO3-BC effectively reduced ≥99.9% of Pb(II) in the polluted irrigation water. The Pb(II) removal mechanisms involved surface electrostatic attraction, ion exchange and surface complexation. These findings conclude that the MoO3-BC is a novel composite that can be used for the removal of Pb from contaminated water. More studies are needed to investigate the potentiality of MoO3-biochar composite for the removal of other metals from water in a mono and competitive sorption system.

Excitotoxic damage to auditory nerve afferents and spiral ganglion neurons is correlated with developmental upregulation of AMPA and KA receptors.

Excess release of glutamate at the inner hair cell-type I auditory nerve synapse results in excitotoxicity characterized by rapid swelling and disintegration of the afferent synapses, but in some cases, the damage expands to the spiral ganglion soma. Cochlear excitotoxic damage is largely mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR) and kainate receptor (KAR) and potentially N-methyl-D-aspartate receptors (NMDAR). Because these receptors are developmentally regulated, the pattern of excitotoxic damage could change during development. To test this hypothesis, we compared AMPAR, NMDAR and KAR immunolabeling and excitotoxic damage patterns in rat postnatal day 3 (P3) and adult cochlear cultures. At P3, AMPAR and KAR immunolabeling, but not NMDAR, was abundantly expressed on peripheral nerve terminals adjacent to IHCs. In contrast, AMPAR, KAR and NMDAR immunolabeling was minimal or undetectable on the SGN soma. In adult rats, however, AMPAR, KAR and NMDAR immunolabeling occurred on both peripheral nerve terminals near IHCs as well as the soma of SGNs. High doses of Glu and KA only damaged peripheral nerve terminals near IHCs, but not SGNs, at P3, consistent with selective expression of AMPAR and KAR expression on the terminals. However, in adults, Glu and KA damaged both peripheral nerve terminals near IHCs and SGNs both of which expressed AMPAR and KAR. These results indicate that cochlear excitotoxic damage is closely correlated with structures that express AMPAR and KAR.

Some Ototoxic Drugs Destroy Cochlear Support Cells Before Damaging Sensory Hair Cells.

A wide variety of ototoxic drugs are capable of damaging the sensory hair cells in the mammalian cochlea resulting in permanent hearing loss. However, the toxic properties of these drugs suggest that some could potentially damage cochlear support cells as well. To test the hypothesis, we treated postnatal day three rat cochlear cultures with toxic doses of gentamicin, cisplatin, mefloquine, and cadmium. Gentamicin primarily destroyed the hair cells and disrupted the intercellular connection with the surrounding support cells. Gentamicin-induced hair cell death was initiated through the caspase-9 intrinsic apoptotic pathway followed by activation of downstream executioner caspase-3. In contrast, cisplatin, mefloquine, and cadmium initially damaged the support cells and only later damaged the hair cells. Support cell death was initiated through the caspase-8 extrinsic apoptotic pathway followed later by downstream activation of caspase-3. Cisplatin, mefloquine, and cadmium significantly reduced the expression of actin and laminin, in the extracellular matrix, leading to significant disarray of the sensory epithelium.

Antioxidative stress-induced damage in cochlear explants.

The imbalance of reactive oxygen species and antioxidants is considered to be an important factor in the cellular injury of the inner ear. At present, great attention has been placed on oxidative stress. However, little is known about fighting oxidative stress. In the current study, we evaluated antioxidant-induced cochlear damage by applying several different additional antioxidants. To determine whether excessive antioxidants can cause damage to cochlear cells, we treated cochlear explants with 50 µM M40403, a superoxide dismutase mimetic, 50 µM coenzyme Q-10, a vitamin-like antioxidant, or 50 µM d-methionine, an essential amino acid and the important antioxidant glutathione for 48 h. Control cochlear explants without the antioxidant treatment maintained their normal structures after incubation in the standard serum-free medium for 48 h, indicating the maintenance of the inherent oxidative and antioxidant balance in these cochlear explants. In contrast, M40403 and coenzyme Q-10-treated cochlear explants displayed significant hair cell damage together with slight damage to the auditory nerve fibers. Moreover, d-methiodine-treated explants exhibited severe damage to the surface structure of hair cells and the complete loss of the spiral ganglion neurons and their peripheral fibers. These results indicate that excessive antioxidants are detrimental to cochlear cells, suggesting that inappropriate dosages of antioxidant treatments can interrupt the balance of the inherent oxidative and antioxidant capacity in the cell.

Stage and histological grade of gastrointestinal stromal tumors based on a new approach are strongly associated with clinical behaviors.

Tumor stage and grade for gastrointestinal stromal tumors are poorly defined. To develop a better evaluation system, we assessed 12 clinical and pathological parameters in 613 patients with follow-up information. These parameters were classified into two gross spread parameters including liver metastasis and peritoneal dissemination, five microscopic spread parameters including lymph node metastasis, vascular, fat, nerve and mucosal infiltration, and five histological parameters including mitotic count > or =10 per 50 high-power fields, muscularis propria infiltration, coagulative necrosis, perivascular pattern and severe nuclear atypia. The 5-year disease-free survival and overall survival of 293 patients without any of these predictive parameters of malignancy were 99 and 100%, respectively. They were regarded as nonmalignant and further evaluations on the stage and grade of these tumors were not performed. At least one and at most seven predictive parameters of malignancy were identified in 320 patients. For these patients, the 5-year disease-free survival and overall survival rates were 44% (mean 6.7 years) and 60% (mean 9.3 years), respectively. The disease-free survival showed significant difference between patients with and without gross spread (P<0.0001), with and without microscopic spread (P=0.0009). Disease-free survival and overall survival were associated with the number of predictive parameters of malignancy in patients without gross spread (P<0.0001 for both disease-free survival and overall survival), but not in patients with gross spread (P=0.882 and 0.441, respectively). Malignant gastrointestinal stromal tumors could be divided into clinical stage I and II based on the absence and presence of gross spread, respectively. The degree of malignancy of patients in clinical stage I could be graded according to the number of predictive parameters of malignancy. Patients in clinical stage II were of the highest degree of malignancy regardless of the number of parameters. We found that the clinical stage and grade were strongly associated with prognosis.

Cochlear hair cell densities in the rabbit.

A typical cochleogram was plotted to investigate hair cell densities as a percentage along the whole length of the basilar membrane (BM) of the rabbit, the length of the BM and the width of the organ of Corti. We generated surface preparations of cochlea from adult, healthy New Zealand White (NZW) rabbits. The numbers of inner hair cells (IHCs) and outer hair cells (OHCs) were counted from images acquired from a digital camera attached to an Olympus light microscope with a scale of 100 µm as a primary unit drawn continuously, and the numbers of IHCs and OHCs were converted to densities at 10% intervals along the length of the cochlea. Meanwhile, the length of the BM and the width of the organ of Corti were calculated. The average length of the cochlea was 14.504 ± 0.403 mm, while the total number of IHCs and the numbers of OHCs in the first, second, and third rows were 1556 ± 13, 1840 ± 47, 1842 ± 46, and 1840 ± 45, respectively, accounting for 21.98%, 26.00%, 26.02%, and 26.00% of the total number of cells, respectively. The densities of each row of OHCs reported in 10% intervals were greater than the densities of the IHCs corresponding to their anatomical locations within the cochlea. The densities of OHCs in each row were distributed uniformly along the BM, while the IHCs densities were not and showed a bimodal distribution with a maximum density at the apex and at 70-80% of the cochlear length from the apex but a lower density in the remaining cochlea. The width of the organ of Corti decreased successively from the apex to the base.

Cytotoxic effects of dimethyl sulphoxide (DMSO) on cochlear organotypic cultures.

The amphipathic molecule dimethyl sulphoxide (DMSO) is a solvent often used to dissolve compounds applied to the inner ear; however, little is known about its potential cytotoxic side effects. To address this question, we applied 0.1-6% DMSO for 24h to cochlear organotypic cultures from postnatal day 3 rats and examined its cytotoxic effects. DMSO concentrations of 0.1% and 0.25% caused little or no damage. However, concentrations between 0.5% and 6% resulted in stereocilia damage, hair cell swelling and a dose-dependent loss of hair cells. Hair cell damage began in the basal turn of the cochlea and spread towards the apex with increasing concentration. Surprisingly, DMSO-induced damage was greater for inner hair cells than outer hair cell whereas nearby supporting cells were largely unaffected. Most hair cell death was associated with nuclear shrinkage and fragmentation, morphological features consistent with apoptosis. DMSO treatment induced TUNEL-positive staining in many hair cells and activated both initiator caspase-9 and caspase-8 and executioner caspase-3; this suggests that apoptosis is initiated by both intrinsic mitochondrial and extrinsic membrane cell death signaling pathways.

Cisplatin-induced vestibular hair cell lesion-less damage at high doses.

Cisplatin, a widely used anticancer drug, damages hair cells in cochlear organotypic cultures at low doses, but paradoxically causes little damage at high doses resulting in a U-shaped dose-response function. To determine if the cisplatin dose-response function for vestibular hair cells follows a similar pattern, we treated vestibular organotypic cultures with doses of cisplatin ranging from 10 to 1000 µM. Vestibular hair cell lesions progressively increased as the dose of cisplatin increased with maximum damage occurring around 50-100 µM, but the lesions progressively decreased at higher doses resulting in little hair cell loss at 1000 µM. The U-shaped dose-response function for cisplatin-treated vestibular hair cells in culture appears to be regulated by copper transporters, Ctr1, ATP7A and ATP7B, that dose-dependently regulate the uptake, sequestration and extrusion of cisplatin.

Ototoxic effects and mechanisms of loop diuretics.

Over the past two decades considerable progress has been made in understanding the ototoxic effects and mechanisms underlying loop diuretics. As typical representative of loop diuretics ethacrynic acid or furosemide only induces temporary hearing loss, but rarely permanent deafness unless applied in severe acute or chronic renal failure or with other ototoxic drugs. Loop diuretic induce unique pathological changes in the cochlea such as formation of edematous spaces in the epithelium of the stria vascularis, which leads to rapid decrease of the endolymphatic potential and eventual loss of the cochlear microphonic potential, summating potential, and compound action potential. Loop diuretics interfere with strial adenylate cyclase and Na+/K+-ATPase and inhibit the Na-K-2Cl cotransporter in the stria vascularis, however recent reports indicate that one of the earliest effects in vivo is to abolish blood flow in the vessels supplying the lateral wall. Since ethacrynic acid does not damage the stria vascularis in vitro, the changes in Na+/K+-ATPase and Na-K-2Cl seen in vivo may be secondary effects results from strial ischemia and anoxia. Recent observations showing that renin is present in pericytes surrounding stria arterioles suggest that diuretics may induce local vasoconstriction by renin secretion and angiotensin formation. The tight junctions in the blood-cochlea barrier prevent toxic molecules and pathogens from entering cochlea, but when diuretics induce a transient ischemia, the barrier is temporarily disrupted allowing the entry of toxic chemicals or pathogens.

Genetic Polymorphism of DNA Methyltransferase 3A rs1550117 A>G and Risk of Cancer: A Meta-analysis.

Numerous studies have investigated the association between DNMT3A rs1550117 A>G polymorphism and cancer risk, but the results are inconsistent. To obtain a more precise evaluation of the relationship, we performed a meta-analysis of 10 case-control studies involving a total of 2184 cancer cases and 3420 controls. Our findings demonstrated a significant association between DNMT3A rs1550117 A>G polymorphism and increased risk of cancer in three genetic models: AA vs. AG + GG (OR, 1.79; 95% CI, 1.12-2.88; p = 0.015), AA vs. GG (OR, 1.81; 95% CI, 1.11-2.95; p = 0.018) and AA vs. AG (OR 1.77; 95% CI 1.13-2.79; p = 0.013). In a stratified analysis by cancer type, significant association between DNMT3A rs1550117 A>G polymorphism and increased risk of colorectal cancer was identified in four genetic models: AA vs. AG + GG (OR, 3.07; 95% CI, 1.56-6.06; p = 0.001), AA vs. GG (OR, 3.16; 95% CI, 1.58-6.29; p = 0.001), AA vs. AG (OR, 2.87; 95% CI, 1.41-5.84; p = 0.004), A vs. G (OR, 1.43; 95% CI, 1.11-1.83; p = 0.005). Furthermore, a stratified analysis by ethnicity, significant increased risk of cancer was found among Asians in three genetic models: AA vs. AG + GG (OR, 1.77; 95% CI, 1.09-2.88; p = 0.022), AA vs. GG (OR, 1.78; 95% CI, 1.08-2.96; p = 0.025), AA vs. AG (OR, 1.75; 95% CI, 1.10-2.79; p = 0.019). No significant publication bias was revealed for the meta-analysis. Sensitivity analysis suggested the reliability of our findings. In conclusion, this meta-analysis suggests that DNMT3A rs1550117 A>G polymorphism may be associated with cancer susceptibility.