CircRNAs: a family number of miRNA regulatory transcriptome in laryngeal carcinoma.

Laryngeal carcinoma (LC) is a common head and neck cancer, which is the result of mutational changes due to gene dysregulation and etiological factors such as tobacco and smoking. A large number of patients received a poor prognosis due to diagnosis at an advanced stage. This highlights the need for definitive, early, and efficient diagnoses. With rapid development of high-throughput sequencing, circular RNA (circRNA) has been reported to play a pivotal role in cancer. CircRNA functions as a microRNA (miRNA) sponge in the regulation of mRNA expression, forming circRNA-miRNA regulatory axis. In this review, we described the axis in LC. The result indicated that CDR1as, hsa_circ_0042823, hsa_circ_0023028, circPARD3, hsa_circ_103862, hsa_circ_0000218, circMYLK, circCORO1C, hsa_circ_100290, circ-CCND1, hsa_circ_0057481, circFLAN, and circRASSF2 expressed higher in LC, whereas, hsa_circ_0036722 and hsa_circ_0042666 expressed lower. The circRNAs regulated the target genes by sponging miRNAs and contributed to the pathogenesis of LC.

Comprehensive analysis of circRNA expression pattern and circRNA-miRNA-mRNA network in oral squamous cell carcinoma.

OBJECTIVE: CircRNAs are critical gene modulators in tumor initiation and progression. However, the expression pattern and molecular pathogenesis of circRNAs in oral squamous cell carcinoma (OSCC) are still poorly characterized. METHODS: RNA sequencing with CIRCexplorer2 pipeline was performed to identify circRNAs in 46 tumor-normal paired tissues from OSCC patients. Another set of 48 head and neck squamous cell carcinoma samples from the MiOncoCirc database were utilized as an independent validation. RESULTS: Of the 1276 identified high-confidence circRNAs, 154 were differentially expressed between tumor and normal tissues (log2|Fold Change|≥1 and false discovery rate < 0.05). CircRNAs expression was globally down-regulated in tumors compared to normal tissues (P = 9.44 × 10-14). Correlation analysis demonstrated that the global expression of circRNAs was positively related to tumor infiltrating lymphocyte (P = 1.10 × 10-4) and stromal signature (P = 2.70 × 10-3) whereas negatively associated with cell proliferation markers (P = 4.32 × 10-2). CircRNAs-miRNAs-mRNAs regulatory network revealed 6574 interactions, and the target genes were enriched in extracellular matrix and immune-related pathways. Survival analysis were performed on target genes in immune-related pathways, and 20 genes were significantly associated with the prognostic status of OSCC in The Cancer Genome Atlas cohort. The risk model constructed with above 20 genes was associated with the prognosis status of OSCC (HR = 3.28, P = 5.06 × 10-11), and the result was validated in an independent study (GSE41613) (HR = 2.06, P = 1.73 × 10-2). CONCLUSION: CircRNAs showed a global down-regulation pattern in OSCC tissues, and genes regulated by circRNAs primarily involved in immune and extracellular matrix pathways, which could also affect the OSCC prognosis, indicating that they may serve as potential prognostic biomarkers.

The improvement of infantile atopic dermatitis during the maintenance period: A multicenter, randomized, parallel controlled clinical study of emollients in Prinsepia utilis Royle.

In order to investigate the effect of daily emollient treatment on infantile atopic dermatitis (AD) during the maintenance period, a total of 309 children younger than 2 years with moderate AD (155 and 154 in the treatment and control groups, respectively) were enrolled in this multicenter, randomized, parallel controlled clinical trial. Subjects were topically treated with desonide cream and emollients in Prinsepia utilis Royle for 2-4 weeks before entering the maintenance period and then differentially treated with either emollients for treatment or none for control. The cumulative maintenance rate, time to flare and improvement of eczema area and severity index (EASI) and infant's dermatitis quality of life index (IDQOL) were evaluated. Results showed that the cumulative maintenance rate of the treatment group (60.5%, 95% CI 50.0-69.4%) was significantly higher than that of the control group (23.5%, 95% CI 15.2-33.0%) (p < .001). The median time to flare in the treatment group was 90 days (interquartile range, IQR 28-90), which was significantly longer than that in the control group (28 days [IQR 18-67]) (p < .001). At Week 4 in the maintenance period, the EASI and IDQOL scores of the treatment group were lower than those of the control group. In conclusion, the application of emollients during the maintenance period of infantile AD can significantly reduce the risk of AD flares, prolong the time to flare and improve the clinical symptoms.

Association of long non-coding RNA MEG3 polymorphisms with oral squamous cell carcinoma risk.

OBJECTIVE: Long non-coding RNA (lncRNA) MEG3 was associated with multiple types of cancers such as oral squamous cell carcinoma (OSCC). Single nucleotide polymorphisms (SNPs) might affect cancer risk by modifying the function of lncRNAs. But fewer study researched the relationship between SNPs and MEG3 in cancers. Considering these reasons, we supposed SNPs in MEG3 may influence the risk of OSCC. MATERIAL AND METHODS: The selected SNPs in MEG3 were genotyped in 1,428 subjects (444 patients with OSCC and 984 cancer-free controls). The relationship between SNPs in MEG3 and OSCC risk was calculated by logistic regression analysis. The function of the SNPs was explored by luciferase activity assay. RESULTS: A statistically significant increased risk was observed between rs11160608 and OSCC (Dominant model: adjusted OR = 1.36, 95% CI = 1.06-1.76, p = 0.017). Moreover, the effect of rs11160608 CC genotype with OSCC risk was much strong in drinkers than non-drinkers (adjusted OR = 1.79, 95% CI = 1.17-2.73, p = 0.007). Furthermore, the luciferase activity of rs11160608 A allele was lower than rs11160608 C allele by luciferase reporter assay. CONCLUSION: Our study confirmed that the SNP rs11160608 in MEG3 might play an important role in OSCC by interring the binding of miRNA.

Imaging study on relationship between the location of lingula and the Gonial angle in a Chinese population.

PURPOSE: The purpose of this study was to investigate the Gonial angle in relation to the position of the lingula using computerized image analysis to guide the oral surgeons to prevent injury to the inferior alveolar nerve and peripheral blood vessels during surgery. METHODS: We measured Gonial angle sizes of bilateral rami and the distances from the lingula tip to the mandibular notch (LN), the anterior (LA) and posterior (LP) margin of the mandibular ramus, the mandibular base (LB) and the occlusive plane (h) in 407 Chinese adults with CBCT. RESULTS: In males, the mean distance of LN was 17.64 mm in the low Gonial angle group while 16.76 mm in the high Gonial angle group, which was significantly different between two groups (P < 0.001). The distance of LA in LGA group was obviously longer than that in HGA group (P < 0.001). The mean distance LP of men was 17.94 mm in LGA group while 16.9 mm in HGA group (P < 0.001). In females, the mean distance of LB in LGA group was 33.32 mm and 32.37 mm in HGA group (P < 0.01). CONCLUSION: We discovered that the segment of the mandibular branch, between the mandibular lingula and the mandibular angle, was obviously smaller in the HGA group than that in the LGA group.

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.

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.

KIT polymorphisms were associated with the risk for head and neck squamous carcinoma in Chinese population.

KITLG/KIT pathway plays a vital role in multiple types of human cancer including head and neck squamous cell carcinoma (HNSCC). Genetic variations in KITLG and KIT may affect the expression or function of these genes, thereby modifying cancer risk. In this study, we evaluated the association of KITLG and KIT polymorphisms with HNSCC risk among Chinese population. Twenty-two tagging SNPs in KITLG and KIT genes were genotyped in a case-control study with 576 HNSCC patients and 1552 healthy controls. Logistic regression analyses revealed that an upstream SNP rs6554198 [additive model: adjusted odds ratio (OR) = 0.85, 95% confidence interval (CI) = 0.74-0.97, P = 0.019] and two intron SNPs rs2237025 (additive model: adjusted OR = 0.82, 95%CI = 0.70-0.95, P = 0.007), and rs17084687 (additive model: adjusted OR = 0.85, 95%CI = 0.73-0.99, P = 0.042) of KIT were significantly associated with the decreased risk of HNSCC. Combined analysis of the three SNPs showed that subjects carrying the protective alleles had decreased risk of HNSCC in a dose-response manner (Ptrend = 0.001). Furthermore, interaction analyses revealed a significant multiplicative interaction between rs17084687 and drinking on HNSCC risk (P = 0.012). Luciferase activity assay indicated that the allele A of potentially functional rs6554198 led to significantly lower transcription activity of KIT compared to the risk allele G. Summarily, our findings suggested that SNPs in KIT gene may play a role in genetic susceptibility to HNSCC, which may improve our understanding of the pathogenic mechanisms of this disease. © 2016 Wiley Periodicals, Inc.

Association of microRNA polymorphisms with the risk of head and neck squamous cell carcinoma in a Chinese population: a case-control study.

BACKGROUND: MicroRNA (miRNA) polymorphisms may alter miRNA-related processes, and they likely contribute to cancer susceptibility. Various studies have investigated the associations between genetic variants in several key miRNAs and the risk of human cancers; however, few studies have focused on head and neck squamous cell carcinoma (HNSCC) risk. This study aimed to evaluate the associations between several key miRNA polymorphisms and HNSCC risk in a Chinese population. METHODS: In this study, we genotyped five common single-nucleotide polymorphisms (SNPs) in several key miRNAs (miR-149 rs2292832, miR-146a rs2910164, miR-605 rs2043556, miR-608 rs4919510, and miR-196a2 rs11614913) and evaluated the associations between these SNPs and HNSCC risk according to cancer site with a case-control study including 576 cases and 1552 controls, which were matched by age and sex in a Chinese population. RESULTS: The results revealed that miR-605 rs2043556 [dominant model: adjusted odds ratio (OR) 0.71, 95% confidence interval (CI) 0.58-0.88; additive model: adjusted OR 0.74, 95% CI 0.62-0.89] and miR-196a2 rs11614913 (dominant model: adjusted OR 1.36, 95% CI 1.08-1.72; additive model: adjusted OR 1.28, 95% CI 1.10-1.48) were significantly associated with the risk of oral squamous cell carcinoma (OSCC). Furthermore, when these two loci were evaluated together based on the number of putative risk alleles (rs2043556 A and rs11614913 G), a significant locus-dosage effect was noted on the risk of OSCC (P trend < 0.001). However, no significant association was detected between the other three SNPs (miR-149 rs2292832, miR-146a rs2910164, and miR-608 rs4919510) and HNSCC risk. CONCLUSION: Our study provided the evidence that miR-605 rs2043556 and miR-196a2 rs11614913 may have an impact on genetic susceptibility to OSCC in Chinese population.

Telomere length, genetic variants and risk of squamous cell carcinoma of the head and neck in Southeast Chinese.

Telomere dysfunction participates in malignant transformation and tumorigenesis. Previous studies have explored the associations between telomere length (TL) and cancer susceptibility; however, the findings are inconclusive. The associations between genetic variants and TL have been verified by quite a few genome-wide association studies (GWAS). Yet, to date, there was no published study on the relationship between TL, related genetic variants and susceptibility to squamous cell carcinoma of the head and neck (SCCHN) in Chinese. Hence, we detected relative telomere length (RTL) by using quantitative PCR and genotyped seven selected single nucleotide polymorphisms by TaqMan allelic discrimination assay in 510 SCCHN cases and 913 controls in southeast Chinese. The results showed that RTL was significantly associated with SCCHN risk [(adjusted odds ratio (OR) = 1.19, 95% confidence interval (CI) = 1.08-1.32, P = 0.001]. Furthermore, among seven selected SNPs, only G allele of rs2736100 related to RTL in Caucasians was significantly associated with both the decreased RTL (P = 0.002) and the increased susceptibility to SCCHN in Chinese (additive model: adjusted OR = 1.17, 95%CI = 1.00-1.38, P = 0.049). These findings provide evidence that shortened TL is a risk factor for SCCHN, and genetic variants can contribute to both TL and the susceptibility to SCCHN in southeast Chinese population.

MicroRNA-101 polymorphisms and risk of head and neck squamous cell carcinoma in a Chinese population.

MicroRNAs (miRNAs) play important roles in regulation of gene expressions and likely have involvement in cancer susceptibility and disease progression. MicroRNA-101 (miR-101) has been well established as a tumor suppressor, and aberrant expression of miR-101 levels has been previously reported in different malignancies including head and neck squamous cell carcinoma (HNSCC). However, the role of single nucleotide polymorphisms (SNPs) of miR-101 in the susceptibility to HNSCC remains unclear. In this study, we genotyped 11 selected SNPs of the miR-101 genes (including miR-101-1 and miR-101-2) in a case-control study including 576 HNSCC cases and 1552 cancer-free controls. For the main effect analysis, none of the 11 selected SNPs was associated with HNSCC risk. However, in the stratification analysis by tumor sites, rs578481 and rs705509 in pri-miR-101-1 were significantly associated with risk of oral squamous cell carcinoma (OSCC) (rs578481: adjusted odds ratio (OR) = 1.19, 95 % confidence interval (CI) 1.01-1.39, P = 0.036; rs705509: adjusted OR = 0.85, 95 % CI 0.73-0.98, P = 0.030). Furthermore, combined analysis of the two SNPs revealed that subjects carrying the risk alleles of rs578481 and rs705509 had increased risk of OSCC in a dose-response manner (P trend = 0.022). Compared with subjects carrying "0-2" risk alleles, subjects carrying "3-4" risk alleles presented a 1.38-fold increased risk of OSCC. In conclusion, our findings suggested that the SNPs rs578481 and rs705509 locating in pri-miR-101-1 may play a role in genetic susceptibility to OSCC, which may improve our understanding of the potential contribution of miRNA SNPs to cancer pathogenesis.

Different levels in alcohol and tobacco consumption in head and neck cancer patients from 1957 to 2013.

OBJECTIVE: To provide a precise quantification of the association between alcohol and tobacco consumption trends in head and neck cancer patients over the past 45 years. METHODS: We combined findings from all studies published until March 2014 and evaluated the association between different levels in alcohol and tobacco consumption and head and neck cancers through a meta-analytic approach. RESULTS: We included 28 studies involving 13830 patients with head and neck cancer. In patients with alcohol consumption, the pooled odds ratio (OR) and 95% confidence interval (CI) were 1.29(1.06-1.57), 2.67(2.05-3.48) and 6.63(5.02-8.74) for light drinkers, moderate drinkers and heavy drinkers, respectively. In patients with tobacco consumption, the pooled OR and 95% CI were 2.33(1.84-2.95), 4.97(3.67-6.71) and 6.77(4.81-9.53) for light smokers, moderate smokers and heavy smokers, respectively. CONCLUSION: The increased alcohol and tobacco consumption trends increased the risk of head and neck cancer over the past 45 years. Tobacco consumption was found to be a stronger risk factor for head and neck cancer than alcohol consumption. Thus, the control should be considered to limit the intake of alcohol and tobacco.

Alcohol dehydrogenase-1B Arg47His polymorphism is associated with head and neck cancer risk in Asian: a meta-analysis.

Head and neck cancers (HNCs) include cancers which arise in oral cavity, pharynx, and larynx. Recent studies have demonstrated that alcohol drinking is an established risk factor for HNC. The alcohol dehydrogenase-1B (ADH1B) plays a major role in the oxidized process of alcohol. To investigate the association of ADH1B Arg47His with HNC in Asian populations, we combined all available studies into a meta-analysis. A total of 2186 cases and 4488 controls were analyzed for this meta-analysis. We used odds ratios (ORs) to assess the strength of the association and 95% confidence intervals (CIs) to give a sense of the precision of the estimate. The ADH1B*47Arg allele was found to be associated with increased risk of HNC in Asians, with the pooled odds ratios (ORs) (Arg/Arg vs. Arg/His + His/His: OR = 2.35, 95% CI = 1.56-3.55, P < 0.0001) in all eight studies. In the subgroup analysis by alcohol consumption, the Arg/Arg vs. Arg/His + His/His genotype was found to be interacted with alcohol consumption, with the OR = 2.44, 95% CI = 1.85-3.20 among ever drinkers. Besides, no significant association was found in non-drinkers. This meta-analysis revealed that ADH1B Arg47His (rs1229984) polymorphism could increase the risk of HNC in Asians significantly.

Genetic variants at 6p21.1 are associated with head and neck cancer in Chinese Han population.

BACKGROUND: A recent study synthesized several published genome-wide association studies (GWAS) on three types of cancers and identified variants at 6p21.1 and 7p15.3 as candidate susceptibility loci for multiple types of human cancers. However, the role of these loci in the development of head and neck cancer (HNC) is still unclear. METHODS: To evaluate the relationships between genetic variants in these regions and HNC risk, we genotyped two common SNPs rs2494938 at 6p21.1 and rs2285947 at 7p15.3 in a case-control study with a total of 503 HNC cases and 900 controls in Han Chinese. RESULTS: We found that rs2494938 at 6p21.1 was associated with a significantly increased risk of HNC in our population [AA vs. GG: adjusted odds ratio (OR)=1.84, 95% confidence interval (CI)=1.13-3.00, P=0.014; AAvs. GA/GG: adjusted OR=1.78, 95% CI=1.10-2.87, P=0.018]. However, no significant association was observed between rs2285947 at 7p15.3 and HNC risk. CONCLUSION: Our results suggest that genetic variants at 6p21.1 may play an important role in HNC development in Han Chinese, and rs2494938 may be a candidate marker for HNC susceptibility.

Genetic variants in let-7/Lin28 modulate the risk of oral cavity cancer in a Chinese Han population.

Let-7 and Lin28 establish a double-negative feedback loop to affect several biological processes, such as differentiation of stem cell, invasion and metastasis, and tumorigenesis. In this study, we systematically investigated the associations between 6 potentially functional SNPs of let7 and Lin28 genes and the risk of oral cavity cancer with a case-control study including 384 oral cavity cancer cases and 731 controls. We found that the variant allele (T) of rs221636 of Lin28B was significantly associated with a reduced risk of oral cavity cancer [odds ratio (OR) = 0.73, 95% confidence interval (CI) = 0.58-0.92, P = 7.55 × 10(-3) in additive model]. Bioinformatics prediction indicated that rs221636 was located at the binding site of hsa-miR-548p in the 3' UTR of Lin28B. Luciferase activity assay also showed a lower expression level for rs221636 T allele compared with A allele. These findings indicated that rs221236 located at Lin28B may contribute to the risk of oral cavity cancer through the interruption of miRNA binding.