Sinensetin protects against periodontitis through binding to Bach1 enhancing its ubiquitination degradation and improving oxidative stress.

Periodontitis is a chronic inflammatory and immune reactive disease induced by the subgingival biofilm. The therapeutic effect for susceptible patients is often unsatisfactory due to excessive inflammatory response and oxidative stress. Sinensetin (Sin) is a nature polymethoxylated flavonoid with anti-inflammatory and antioxidant activities. Our study aimed to explore the beneficial effect of Sin on periodontitis and the specific molecular mechanisms. We found that Sin attenuated oxidative stress and inflammatory levels of periodontal ligament cells (PDLCs) under inflammatory conditions. Administered Sin to rats with ligation-induced periodontitis models exhibited a protective effect against periodontitis in vivo. By molecular docking, we identified Bach1 as a strong binding target of Sin, and this binding was further verified by cellular thermal displacement assay and immunofluorescence assays. Chromatin immunoprecipitation-quantitative polymerase chain reaction results also revealed that Sin obstructed the binding of Bach1 to the HMOX1 promoter, subsequently upregulating the expression of the key antioxidant factor HO-1. Further functional experiments with Bach1 knocked down and overexpressed verified Bach1 as a key target for Sin to exert its antioxidant effects. Additionally, we demonstrated that Sin prompted the reduction of Bach1 by potentiating the ubiquitination degradation of Bach1, thereby inducing HO-1 expression and inhibiting oxidative stress. Overall, Sin could be a promising drug candidate for the treatment of periodontitis by targeting binding to Bach1.

Enhancing Idiopathic Scoliosis Patients' Outcomes Through Functional Rehabilitation Training in Combination with Orthosis.

Objective: This study aims to provide clinical evidence for the treatment of idiopathic scoliosis (IS) by assessing the therapeutic effectiveness of combining functional rehabilitation training with orthosis. Methods: We enrolled a total of 94 IS patients who were admitted to our hospital from April 2020 to February 2022. These patients were randomly assigned into two groups: a research group (RG; n=47) receiving functional rehabilitation training combined with orthosis and a control group (CG; n=47) receiving orthosis treatment alone. Clinical outcomes were evaluated one year after treatment. We also measured the Cobb angle, apical vertebral rotation (AVR), and the distance between the vertical line of the sacrum and the spinous process of the scoliosis parietal vertebra before and after treatment to determine apical vertebral translation (AVT) from the sacral midline and lumbar range of motion (ROM). Patient quality of life was assessed using the Short-Form 36 Item Health Survey (SF-36). Results: After treatment, the research group exhibited significantly lower Cobb angles, AVR, and AVT, along with a higher overall response rate and greater lumbar ROM compared to the control group (P < .05). Post-treatment SF-36 scores increased in both groups, with notably higher scores in the research group (P < .05). Conclusions: Combining functional rehabilitation training with orthosis is an effective approach for the treatment of IS and holds substantial clinical significance.

Advanced extracellular vesicle bioinformatic nanomaterials: from enrichment, decoding to clinical diagnostics.

Extracellular vesicles (EVs) are membrane nanoarchitectures generated by cells that carry a variety of biomolecules, including DNA, RNA, proteins and metabolites. These characteristics make them attractive as circulating bioinformatic nanocabinets for liquid biopsy. Recent advances on EV biology and biogenesis demonstrate that EVs serve as highly important cellular surrogates involved in a wide range of diseases, opening up new frontiers for modern diagnostics. However, inefficient methods for EV enrichment, as well as low sensitivity of EV bioinformatic decoding technologies, hinder the use of EV nanocabinet for clinical diagnosis. To overcome these challenges, new EV nanotechnology is being actively developed to promote the clinical translation of EV diagnostics. This article aims to present the emerging enrichment strategies and bioinformatic decoding platforms for EV analysis, and their applications as bioinformatic nanomaterials in clinical settings.

Knockdown of Bach1 protects periodontal bone regeneration from inflammatory damage.

Periodontal bone regeneration is a major challenge in the treatment of periodontitis. However, the regenerative vitality of periodontal ligament cells (PDLCs) declines in the environment of periodontitis and accompanying oxidative stress. This study aimed to investigate the functional mechanisms of Bach1, a transcriptional suppressor involved in oxidative stress response, and its regulation of PDLC osteogenesis under inflammatory conditions. We observed a significant elevation in Bach1 expression in periodontal tissues with periodontitis and PDLCs under inflammatory conditions. Knockdown of Bach1 alleviated the inflammation-induced oxidative stress level and partly offset the inhibitory effect of inflammatory conditions on osteogenesis, as well as the expression of osteogenic genes BMP6, OPG and RUNX2. Similarly, knockdown of Bach1 protects PDLCs from inflammatory damage to periodontal bone regeneration in vivo. Furthermore, we found that Bach1 could bind to the histone methyltransferase EZH2, and the binding increased under inflammatory conditions. Bach1 enhanced the ability of EZH2 to catalyse H3K27me3 on the promoter region of RUNX2 and BMP6, thus repressing the expression of osteoblastic genes. In conclusion, our study revealed that knockdown of Bach1 effectively rescued the osteogenesis and oxidative stress of PDLCs with inflammation. Bach1 could be a promising target for enhancing periodontal tissue regeneration under periodontitis conditions.

Natural compound fraxinellone ameliorates intestinal fibrosis in mice via direct intervention of HSP47-collagen interaction in the epithelium.

Intestinal fibrosis is a common complication of inflammatory bowel disease. There is still a lack of effective drugs for the prevention or treatment of intestinal fibrosis. Heat shock protein 47 (HSP47) plays a key role in the development of intestinal fibrosis. In this study we investigated the therapeutic potential and underlying mechanisms of fraxinellone, a degraded limonoid isolated from the root bark of Dictamnus dasycarpus, in the treatment of intestinal fibrosis. Intestinal fibrosis was induced in mice by dextran sodium sulfate (DSS) treatment. DDS-treated mice were administered fraxinellone (7.5, 15, 30 mg·kg-1·d-1, i.g.) for 45 days. We showed that fraxinellone administration dose-dependently alleviated DSS-induced intestinal impairments, and reduced the production of intestinal fibrosis biomarkers such as α-smooth muscle actin (SMA), collagen I, hydroxyproline, fibronectin and laminin, and cytokines such as TGF-ß, TNF-α and IL-ß. We then established in vitro intestinal fibrosis cell models in SW480 and HT-29 cells, and demonstrated that treatment with fraxinellone (3, 10, 30 µM) significantly relieved TGF-ß-induced fibrosis responses by inhibiting the TGF-ß/Smad2/3 signaling pathway. Molecular docking suggested that the fraxinellone might disrupt the interaction between HSP47 and collagen, which was confirmed by coimmunoprecipitation experiments. SPR analysis showed that fraxinellone had a high affinity for HSP47 with a Kd value of 3.542 × 10-5 M. This study provides a new example of HSP47-collagen intervention by a natural compound and has important implications for the clinical treatment of inflammation-induced issue fibrosis.

Bioinspired skin towards next-generation rehabilitation medicine.

The rapid progress of interdisciplinary researches from materials science, biotechnologies, biomedical engineering, and medicine, have resulted in the emerging of bioinspired skins for various fantasticating applications. Bioinspired skin is highly promising in the application of rehabilitation medicine owing to their advantages, including personalization, excellent biocompatibility, multi-functionality, easy maintainability and wearability, and mass production. Therefore, this review presents the recent progress of bioinspired skin towards next-generation rehabilitation medicine. The classification is first briefly introduced. Then, various applications of bioinspired skins in the field of rehabilitation medicine at home and abroad are discussed in detail. Last, we provide the challenges we are facing now, and propose the next research directions.

Changes in N6-methyladenosine RNA methylomes of human periodontal ligament cells in response to inflammatory conditions.

OBJECTIVE: To investigate the changes in the m6A methylation modification profile of human periodontal ligament cells (hPDLCs) in response to inflammatory conditions. BACKGROUND: Periodontitis is an infectious disease of the periodontal support tissue that leads to the loss of alveolar bone. HPDLCs are primary cells that can repair periodontal tissue defects caused by periodontitis. However, the inflammatory conditions induce inflammatory damage and decrease ossification of hPDLCs. This inflammatory response depends on genetic and epigenetic mechanisms, including m6A methylation. METHODS: HPDLCs were cultured with osteogenic induction medium (NC group), while TNF-α (10 ng/mL) and IL-1ß (5 ng/mL) were added to simulate inflammatory conditions (Inflam group). Then RNA-seq and MeRIP-seq analyses were performed to identify m6A methylation modification in the transcriptome range of hPDLCs. RESULTS: The results showed that the osteogenic differentiation of hPDLCs was inhibited under inflammatory conditions. RNA-seq analysis also revealed that the decreased genes in response to inflammatory conditions were primarily annotated in processes associated with ossification. Compared with the NC group, differentially m6A-methylated genes were primarily enriched in histone modification processes. Among 145 histone modification genes, 25 genes have been reported to be involved in the regulation of osteogenic differentiation, and they include KAT6B, EP300, BMI1, and KDMs (KDM1A, KDM2A, KDM3A, KDM4B, and KDM5A). CONCLUSION: This study demonstrated that the m6A landscape of hPDLCs was changed in response to inflammation. M6A methylation differences among histone modification genes may act on the osteogenic differentiation of hPDLCs.

Role of Intestinal Microbes in Chronic Liver Diseases.

With the recent availability and upgrading of many emerging intestinal microbes sequencing technologies, our research on intestinal microbes is changing rapidly. A variety of investigations have found that intestinal microbes are essential for immune system regulation and energy metabolism homeostasis, which impacts many critical organs. The liver is the first organ to be traversed by the intestinal portal vein, and there is a strong bidirectional link between the liver and intestine. Many intestinal factors, such as intestinal microbes, bacterial composition, and intestinal bacterial metabolites, are deeply involved in liver homeostasis. Intestinal microbial dysbiosis and increased intestinal permeability are associated with the pathogenesis of many chronic liver diseases, such as alcoholic fatty liver disease (AFLD), non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), chronic hepatitis B (CHB), chronic hepatitis C (CHC), autoimmune liver disease (AIH) and the development of hepatocellular carcinoma (HCC). Intestinal permeability and dysbacteriosis often lead to Lipopolysaccharide (LPS) and metabolites entering in serum. Then, Toll-like receptors activation in the liver induces the exposure of the intestine and liver to many small molecules with pro-inflammatory properties. And all of these eventually result in various liver diseases. In this paper, we have discussed the current evidence on the role of various intestinal microbes in different chronic liver diseases. As well as potential new therapeutic approaches are proposed in this review, such as antibiotics, probiotics, and prebiotics, which may have an improvement in liver diseases.

Clinical analysis on the root fracture of the maxillary first molar.

OBJECTIVES: This study aimed to investigate the common types and directions of root fractures of the maxillary first molar and the influence of root canal treatment on the prevalent sites of root fractures. METHODS: A total of 274 maxillary first molars with root fractures diagnosed via cone beam computed tomography were included. The root fractures of nonendodontically and endodontically treated teeth were identified to be spontaneous and secondary root fractures, respectively. The sites, types, and directions of spontaneous and secondary root fractures were determined. RESULTS: Among the spontaneous root fractures, the proportion of palatal root fractures (56.1%) was higher than those of mesial buccal root fractures (36.1%) and distal buccal root fractures (7.8%). Among the secondary root fractures, the proportion of mesial buccal root fractures (52.7%) was higher than those of palatal root fractures (36.5%) and distal buccal root fractures (10.8%). The distribution of predominant fracture sites was statistically significant (P<0.05), and vertical root fracture was the most common type. Palatal and buccal roots were commonly fractured at the mesiodistal and buccal-palatal directions, respectively. CONCLUSIONS: This study provided an epidemiological basis for the clinical features of root fractures of the maxillary first molar. During the dia-gnosis and treatment of the maxillary first molar, the possibility of palatal root fractures should be considered. The occurrence of mesial buccal root fractures may be related to root canal treatment. Therefore, the risk of mesial buccal root fractures caused by iatrogenic factors should be minimized.

Circular RNA-ABCB10 promotes angiogenesis induced by conditioned medium from human amnion-derived mesenchymal stem cells via the microRNA-29b-3p/vascular endothelial growth factor A axis.

The powerful ability of human amnion-derived mesenchymal stem cells (hAMSCs) to promote angiogenesis suggests that they may facilitate angiogenesis-associated therapeutic strategies. However, the molecular mechanisms underlying hAMSC-induced angiogenesis remain largely unknown. The present study results suggested that enhanced migration and tube formation in human umbilical vein endothelial cells (HUVECs) was induced by conditioned medium from hAMSCs (hAMSC-CM). In addition, culture with this conditioned medium resulted in the increased expression of circular RNA ATP binding cassette subfamily B member 10 (circ-ABCB10) and vascular endothelial growth factor A (VEGFA). In the present study genes related to thecirc-ABCB10/microRNA (miR)-29b-3p/VEGFA pathway were predicted using bioinformatics software, and further investigated using in vitro luciferase reporter assays. Loss-of-function assays were performed using small interfering RNAs (siRNAs). The results suggested that siRNA-silencing of circ-ABCB10 in HUVECs weakened migration and tube formation of HUVECs following hAMSC-CM treatment and reduced the levels of VEGFA expression. Treatment with an miR-29b-3p inhibitor could largely rescue these effects in HUVECs, following circ-ABCB10 silencing. The present study results suggest that the circ-ABCB10/miR-29b-3p/VEGFA pathway may be involved in the pro-angiogenic role of hAMSC-CM in HUVECs.

Uncoupling protein-2 regulates M1 macrophage infiltration of gingiva with periodontitis.

Periodontitis is an inflammatory disease accompanied by alveolar bone loss. Moreover, M1 macrophages play a critical role in the development of periodontal disease. Uncoupling protein-2 (UCP2) is a mitochondrial transporter protein that controls M1 macrophage activation by modulating reactive oxygen species (ROS) production. We investigated the role of UCP2 in M1 macrophage infiltration in gingival tissues with periodontitis. We found that the expression of UCP2 was upregulated in M1 macrophages infiltrating human periodontal tissues with periodontitis. Macrophage-specific knockout of UCP2 could increase the infiltration of macrophage and exacerbate inflammatory response in a mouse gingiva affected with periodontitis, induced by Porphyromonas gingivalis-LPS (Pg-LPS) injection. The loss of UCP2 may contribute to the enhanced abilities of proliferation, migration, pro-inflammatory cytokine secretion, and ROS production in Pg-LPS-treated macrophages. Our results indicate that UCP2 has an important role in M1 macrophage polarization in the periodontal tissue with periodontitis. It might be helpful to provide theoretical basis for design of new therapeutic strategies for periodontitis.

LncRNA H19 Knockdown in Human Amniotic Mesenchymal Stem Cells Suppresses Angiogenesis by Associating with EZH2 and Activating Vasohibin-1.

Human amniotic mesenchymal stem cells (HAMSCs) are promising seed cells with great advantages in promoting angiogenesis. However, the mechanisms underlying angiogenesis facilitated by HAMSCs are still unclear. Long noncoding RNA H19 is involved in many biological processes, such as enhancing angiogenesis and proliferation, invasion, and migration of cancer cells. In this study, we constructed HAMSCs of stable low-expression H19 (HAMSC-shH19) and the scramble control (HAMSC-shNC) using lentiviral vectors, and in a three-dimensional coculture with human umbilical vein endothelial cells (HUVECs) to investigate the effect of H19 knockdown in HAMSCs on angiogenesis. Our results demonstrated that H19 knockdown significantly inhibited the angiogenic function of HAMSCs at an early stage in vitro and in vivo. The results of CCK8 and transwell assays demonstrated that the conditioned medium secreted by HAMSCs reduced proliferation and migration of HUVECs after downregulating H19. The angiogenesis factors expressed and secreted by HAMSC-shH19 were decreased compared with those secreted by the control, while angiogenesis inhibitors were elevated. Furthermore, we conducted chromatin immunoprecipitation and RNA-binding protein immunoprecipitation assays and found that H19 could interact with the histone methyltransferase Enhancer of Zeste homolog 2 (EZH2) and that H19 knockdown inhibited the ability of EZH2 to recruit methyl groups to the promoter region of the angiogenesis inhibitor gene vasohibin-1 (VASH1), thus increasing VASH1 expression and secretion of HAMSCs, suppressing angiogenesis. In summary, our study identified H19 as an important regulator in HAMSCs for promoting angiogenesis, which would help to construct ideal gene-modified seed cells to enhance angiogenesis in regenerative medicine.

Composite of Gadolinium-Labeled Dendrimer Nanocluster And Graphene Oxide Nanosheet for Highly Efficient Liver T1-Weighted Imaging Probe.

Magnetic resonance contrast agent employs the use of gadolinium chelates, which has many limitations for clinical use including a low contrast effect, a short diagnostic window, and a brief blood circulation time. On this basis, we designed a gadolinium-labeled dendrimer nanocluster (GdDN) loaded graphene oxide nanosheet (GO-GdDN) to boost T1 contrast ability for imaging in vivo and improve blood circulation time. GO-GdDN presented an ultrahigh r1 relaxivity up to 19.07 mM-1 s-1 in a 9.4 T MR scanner, and a bright contrast image in vitro experiment. In addition, GO-GdDN could be internalized by HepG2 cells and presented strong cell contrast enhancement and reduction of the T1 value in HepG2 cells. In vivo, the retention time of GO-GdDN was significantly improved, so that the accumulation of GO-GdDN in liver was enhanced. Moreover, compared to Gd-DTPA, systemic delivery of GO-GdDN dramatically enhanced the signal-to-noise ratio of liver images, which was helpful for accurate imaging of liver and detection of liver lesions in vivo. Thus, this study demonstrates the utility of a powerful diagnosis tool for liver tumor or lesions.

Genetic variants in lncRNA H19 are associated with the risk of oral squamous cell carcinoma in a Chinese population.

To evaluate whether the genetic variants in H19 influence the risk of oral squamous cell carcinoma (OSCC) in a Chinese population, a case-control study was conducted to analyze four functional single nucleotide polymorphisms (SNPs) in H19. The cohort comprised of 444 OSCC cases and 984 healthy controls, and the study further evaluated the biological effect by bioinformatics prediction and functional experiments. Two SNPs, rs217727 and rs2839701, were found to be associated with the risk of OSCC [rs217727: odds ratio (OR) = 1.32, 95% confidence interval (CI) = 1.11-1.58, P = 0.002; rs2839701: OR = 1.23, 95% CI = 1.04-1.46, P = 0.019].Bioinformatics predicted that rs2839701 C>G might alter the secondary structure of H19. In addition, rs2839701 C>G inhibited the transcription activity and was correlated with the decreased expression of downstream gene MRPL23-AS1 that was downregulated in OSCC. The current results suggested that the SNPs in H19 may play a major role in genetic susceptibility to OSCC.

ATG12 expression quantitative trait loci associated with head and neck squamous cell carcinoma risk in a Chinese Han population.

Autophagy is an essential process to maintain cellular homeostasis and functions, which has been demonstrated to play an important role in the different stages of tumorigenesis. To evaluate whether the genetic variants in autophagy-related genes influence the head and neck squamous cell carcinoma (HNSCC) risk, we conducted a case-control study to analyze 11 tagging single nucleotide polymorphisms (SNPs) of three core autophagosome formation genes (ATG5, ATG12, and ATG16L1) with 576 HNSCC cases and 1552 healthy controls among Chinese population. Finally, we identified that rs26537 of ATG12 (additive model: adjusted odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.03-1.37, P = 0.017) and rs4663402 in ATG16L1 (additive model: adjusted OR = 1.39, 95%CI = 1.08-1.80, P = 0.010) were significantly associated with the increased risk of HNSCC. However, no association was detected between other SNPs and HNSCC risk. The results of expression quantitative trait loci (eQTL) analysis based on Genotype-Tissue Expression (GTEx) accessible data, showed that the risk allele of rs26537 was significantly associated with up-regulated expression of ATG12 (P = 0.0021). Further luciferase activity assay indicated that rs26537 T > C in ATG12 intron one region significantly enhanced transcription activity. These results suggested that ATG12 eQTL SNP rs26537 might contribute to an allele-specific effect on the expression of host gene ATG12 and explain a fraction of HNSCC genetic susceptibility.

Chk2 deficiency alleviates irradiation-induced taste dysfunction by inhibiting p53-dependent apoptosis.

OBJECTIVE: Taste dysfunction is one of the most common complications following radiotherapy, which leads to decreased appetite and life quality of patients suffering from head and neck cancer. The aim of this study was to investigate the role of checkpoint kinase 2 (Chk2) deficiency in irradiation-induced taste dysfunction. MATERIALS AND METHODS: Alterations in oxidative stress, DNA damage, and potential signaling pathway were compared between Chk2-deficient (Chk2-/- ) mice and their wild-type (WT) littermates pre-irradiation and 7 and 30 days postirradiation by biochemistry and immunohistochemistry. RESULTS: Chk2-/- mice showed less loss of type II and type III taste cells, lower expression of p53, caspase-3, and cleaved caspase-3, and lower apoptosis levels. However, no significant differences in H2 O2 and MDA concentrations, T-SOD and GSH-Px activities, and expression of SOD1, SOD2, and 8-OHdG were detected in the taste buds of Chk2-/- mice as compared to those of WT mice. CONCLUSION: Chk2 deficiency downregulated the expression of p53 and inhibited cellular apoptosis, partly contributing to the radioprotective effect on taste cells, but did not alter oxidative stress levels, antioxidant ability, and oxidative DNA damage in taste buds.

Association between BRCA1 P871L polymorphism and cancer risk: evidence from a meta-analysis.

Breast cancer 1 (BRCA1) gene makes great contributions to the repair of DNA. The association between BRCA1 P871L polymorphism and cancer risk has been investigated in a growing number of studies, but the conclusions are not conclusive. To obtain a comprehensive conclusion, we performed a meta-analysis of 24 studies with 13762 cases and 22388 controls. The pooled results indicated that BRCA1 gene P871L variant decreased risk of overall cancer (homozygous model: odds ratio (OR) = 0.89, 95%confidence interval (CI) = 0.79-1.00; recessive model: OR = 0.89, 95% CI = 0.80-0.99). The stratified analysis observed decreased risk associated with BRCA1 P871L in subgroups among Asians and high score studies, but not Caucasians or low score studies. In conclusion, despite several limitations, this meta-analysis suggested that BRCA1 P871L genetic variation may be associated with decreased susceptibility to cancer.

[An anatomical study of maxillary sinus septum of Han population in Jiangsu region using cone-beam CT].

PURPOSE: To examine the anatomical variation of maxillary sinus septum of Han nationality in Jiangsu region by using cone-beam computed tomography (CBCT) combined with Simplant software in order to provide anatomical basis and operation instruction for oral implants after maxillary sinus lifting. METHODS: CBCT image data were collected from 424 patients for analysis of maxillary sinus septa. Digital imaging and communications in medicine (Dicom) image files were fed into the computer-aided Simplant software and used to analyze the prevalence, location, height, orientation, and morphology of maxillary sinus septa through three-dimensional reconstruction. The data was analyzed with SPSS17.0 software package. RESULTS: The proportion of the occurrence of maxillary sinus septa in 424 subjects was 44.81% and 21.23% of the subjects (n=90) had multiple sinus septa, while 20.52% had bilateral sinus septa (n=87). Totally 848 maxillary sinuses were observed in this study and 277 sinuses had septa with a proportion of 32.67%. The prevalence of septa was not significantly related to gender, age, and the presence or absence of teeth. Septa were located most frequently in the middle of maxillary sinus (59.94%). The mean height of sinus septa was (5.90±3.65) mm and (5.54±2.87) mm in the right and left maxillary sinus, respectively. The mean length of sinus septa was (8.15±2.40) mm and (7.88±2.73) mm in the right and left maxillary sinus, respectively. CONCLUSIONS: Nearly 44.81% of Han population in Jiangsu region have maxillary sinus septa. The CBCT imaging technique can provide comprehensive and accurate quantitative analysis of maxillary sinus septa and is meaningful to provide anatomical basis and clinical guidance before sinus augmentation procedures.

Genetic variants at 4q23 and 12q24 are associated with head and neck cancer risk in China.

A recent genome-wide association study (GWAS) reported significant associations of several novel genetic variants with risk of upper aerodigestive tract (UADT) cancers including head and neck cancer (HNC) in Europeans. However, these findings have not been confirmed in other populations including Chinese. According to the findings from the GWAS and other publications, we genotyped six genetic variants (rs1494961, rs1229984, rs1789924, rs971074, rs4767364, and rs671) in a case-control study with 397 HNC cases and 900 controls in China, by using the TaqMan allelic discrimination assay. We found that rs1229984 at 4q23 significantly increased the risk of HNC [dominant model: adjusted odds ratio (OR) = 1.34, 95% confidence interval (CI) = 1.05-1.71; additive model: adjusted OR = 1.24, 95% CI = 1.04-1.50], while rs671 at 12q24 significantly decreased the risk of HNC (recessive model: adjusted OR = 0.46, 95% CI = 0.25-0.85). Furthermore, when these two loci were evaluated together by the number (0-4) of putative risk alleles (rs1229984 G and rs671 G), a significant locus-dosage effect was found between the groups and risk of HNC (Ptrend = 0.016). Compared with the "0-1" group, groups with "2" risk alleles and "3-4" risk alleles significantly increased the risk of HNC with adjusted ORs of 1.17 (95% CI = 0.84-1.64) and 1.51 (95% CI = 1.06-2.15), respectively. However, no significant association was detected between other four variants (rs1494961, rs1789924, rs971074, and rs4767364) and HNC risk. These findings suggest that rs1229984 at 4q23 and rs671 at 12q24 may serve as candidate markers for susceptibility to HNC in Chinese population.

Genetic variants at 10q23 are associated with risk of head and neck cancer in a Chinese population.

BACKGROUND: A recent genome-wide association study (GWAS) focused on esophageal squamous cell carcinoma (ESCC) has identified several susceptible regions (5q11, 21q22, 6p21 10q23, and 12q24) in Chinese population. We hypothesized that single nucleotide polymorphisms (SNPs) identified in these regions for ESCC were also associated with the risk of head and neck cancer (HNC) which share similar risk factors with ESCC. METHODS: To test this hypothesis, we genotyped three SNPs (rs2274223, rs2014300 and rs10484761) in a case-control study with 503 HNC cases and 900 cancer-free controls in a Chinese population. RESULTS: We found that rs2274223 was associated with a significantly increased risk of HNC in our population [GG vs. AA: adjusted odds ratio (OR)=1.86, 95% confidence interval (CI)=1.09-3.16; GG vs. (AG/AA): adjusted OR=1.85, 95% CI=1.09-3.12], and the effect appeared to be more prominent among drinkers (P=0.024) and patients with oral cavity cancer (P=0.019). In contrast, rs2014300 and rs10484761 variant were not observed any significantly association with risk of HNC. CONCLUSIONS: These results indicate that rs2274223 may be a marker SNP for HNC susceptibility in Chinese population.