Oral Squamous Cell Carcinoma Susceptibility Research Articles

Association of single nucleotide polymorphism miRNA-146a (rs2910164) with increased predisposition to oral squamous cell carcinoma in central India population.

miRNAs play a crucial role in the genesis of cancer, either as tumor suppressor genes or as oncogenes. Single Nucleotide Polymorphisms (SNPs) in the seed region of microRNAs (miRNAs) can dysregulate their levels in the tissues and thereby affect carcinogenesis. The association of SNP in miR-146a (rs2910164) with the risk of oral squamous cell carcinoma (OSCC) has not been understood. In the present study, we have determined the association and functional significance of miR-146a (rs2910164) SNP with susceptibility to OSCC predisposition. In the present case-control study, we enrolled 430 subjects from central India (215 OSCC cases and 215 healthy controls). We performed genotyping by Kompetitive Allele Specific PCR (KASP), and their correlation with OSCC susceptibility was analyzed. miRNA expression profiling in tumor tissues and adjacent normal tissues from six OSCC patients was done by a NanoString n-Counter-based assay. Subsequently, gene ontology and pathway analysis were performed with FunRich version 3.13. The CC genotype of rs2910164 miR-146a was significantly associated with the increased risk for OSCC (CC vs GC, OR = 2.62; 95% CI: 1.48-4.66; p value = 0.001). However, the GC genotype was protective with GC vs CC (OR = 0.38, 95%CI =0.21-0.67, p-value = 0.001), and GC vs GG (OR = 0.58, 95%CI = 0.37-0.89, p-value = 0.01). Our finding suggests that SNP rs2910164 of miR-146a may be a genetic risk factor for OSCC susceptibility in the Central India population. However, more extensive multicenter studies are required to validate these findings.

Effect of CDH1 and CDH2 genes polymorphisms in oral squamous cell carcinoma susceptibility in a sample of Iranian population: A case‐control study

Oral squamous cell carcinoma (OSCC) is a global malignant epithelial neoplasm affecting the oral cavity. Cadherins, as an adhesion molecule, are involved in cell-cell interaction. We aim to study the effect of two cadherin polymorphisms on OSCC risk in southeast of Iran. In this case-control study, 94 individuals (47 OSCC cases and 47 controls), that referred to the Department of Oral Pathology, Faculty of Dentistry, Zahedan University of Medical Sciences, Iran were included. Cadherin single nucleotide polymorphisms CDH1 (rs16260) and CDH2 (rs11564299) were genotyped by the tetra-Amplification Refractory Mutation System-PCR technique. N-cadherin genotyping showed that the AA, AG, and AG + GG were presented 78.7%, 17%, 21.3% versus 66%, 29.7%, 34% in the cases and the control group, respectively. AG genotype was more common in control than case (OR = 0.47, 95% CI: 0.17-1.29, p = 0.14). G allele was more prevalent in control (19.1%) than the case group (12.8%) (OR = 0.61, 95% CI: 0.27-1.36, p = 0.23). In E-cadherin, AC, AA, and AC + AA genotypes frequency were 17%, 12.8%, and 29.8% in case versus 8.5%, 8.5%, and 17% in the control group. Allele A was more common in the case than the control group (OR = 1.84, 95% CI: 0.84-4.03, p = 0.12). Also, AA and CC, the codominant genotypes were common in CDH2 and CDH1 respectively in all histopathological grades, and no statically significant association was observed between OSCC different histopathological grades and cadherin genotypes (p = 0.39 in N-cadherin, p = 0.74 in E-cadherin). Our results showed a lack of association between CDH1 and CDH2 gene polymorphisms with OSCC risk in a population of Southeastern of Iran.

Association of genetic variants of CircCHST15 with oral squamous cell carcinoma in the Chinese Han population.

Oral squamous cell carcinoma (OSCC) is the most common cancer in the oral cavity. The relationship between the genetic susceptibility of circCHST15 and OSCC remains unclear. Genetic variants of circCHST15 were screened using a genotyping analysis from 1044 patients with OSCC and 3199 healthy participants. The circCHST15 expression was detected in 32 pairs of OSCC tissues. The circular RNA quantitative trait locus analysis and the reporter gene assay were performed for verification. The circCHST15 expression was upregulated in OSCC (Wilcoxon p < 1e-3). The genotyping analysis screened out 61 loci in circCHST15 associated with the risk of OSCC. After adjustment and annotation, rs28707473 (A > C, odds ratio=1.21, 95% CI: 1.076-1.361, p=1.453e-3) was selected. This genetic variation could elevate the circCHST15 expression level possibly by altering the structure of circular RNAs and affecting transcription factor binding. The results of this study suggested that genetic variants of circCHST15 may contribute to OSCC susceptibility.

Combined impacts of histamine receptor H1 gene polymorphisms and an environmental carcinogen on the susceptibility to and progression of oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is the most frequently encountered type of oral cancer. Histamine receptor H1 (HRH1) was reported to play a crucial role in OSCC carcinogenesis, but impacts of genetic variants of HRH1 on OSCC remain unclear. Herein, we investigated the association between functional single-nucleotide polymorphisms (SNPs) of HRH1 and OSCC susceptibility or clinicopathologic variables by logistic regression models. HRH1 genotypes at four loci (rs346074, rs346076, rs901865, and rs2606731) were analyzed by a TaqMan allelic discrimination assay, and we found that patients harboring HRH1 rs901865 T and rs346074 T alleles had a significantly lower risk of developing larger tumor sizes (>T2) under a dominant model. Based on the environmental carcinogen exposure status, we observed that HRH1 rs901865 polymorphic variants were also associated with a lower risk of developing more-advanced clinical stages (III or IV) in patients with a betel-quid-chewing habit. Moreover, genotype screening of rs901865 and rs346074 in OSCC cell lines showed that cells respectively carrying the CT and TT genotypes expressed lower HRH1 levels compared to cells carrying the CC genotype of rs901865 and rs346074. Furthermore, analyses of TCGA and GEO databases revealed that HRH1 expression levels were upregulated in head and neck squamous cell carcinoma (HNSCC) and OSCC tissues compared to normal tissues and were correlated with larger tumor sizes and poorer prognoses. These results indicated the involvement of HRH1 SNPs rs901865 and rs346074 in OSCC development and support the interaction between HRH1 gene polymorphisms and an environmental carcinogen as a predisposing factor for OSCC progression.

Combined Impacts of Genetic Variants of Long Non-Coding RNA MALAT1 and the Environmental Carcinogen on the Susceptibility to and Progression of Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the oral cavity, and long non-coding (lnc)RNA of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was recently reported to play a crucial role in OSCC development and progression. However, potential effects of genetic variants of MALAT1 on the development of OSCC are still unclear. Herein, we performed a case-control study in 1350 patients with OSCC and 1199 healthy controls to evaluate the association between functional single-nucleotide polymorphisms (SNPs) of MALAT1 and OSCC susceptibility, as well as its clinicopathologic characteristics. A TaqMan allelic discrimination assay was used to genotype four tagging SNPs, viz., rs3200401 C>T, rs619586 A>G, rs1194338 C>A, and rs7927113 G>A, and results showed that the MALAT1 rs3200401 T allele had a lower risk of OSCC (adjusted odds ratio (AOR): 0.779, 95% confidence interval (CI): 0.632~0.960, p=0.019) and a higher risk of developing moderately (grade II)/poorly (grade III) differentiated OSCC (AOR: 1.508-fold, 95% CI: 1.049~2.169, p=0.027) under a dominant model. According to environmental carcinogen exposure, patients with a betel quid-chewing habit who carried the T allele of rs3200401 more easily developed high-grade (II/III) OSCC (AOR: 1.588, 95% CI: 1.055~2.390, p=0.027), and patients with the same genotype but who did not chew betel quid had a lower risk of developing lymph node metastasis (AOR: 0.437, 95% CI: 0.255~0.749, p=0.003). In addition to rs3200401, the rs619586 AG/GG genotype was associated with increased risks of developing advanced stages (III+IV) and larger tumor sizes (>T2) compared to the AA genotype, especially in the subgroup of betel quid chewers. Furthermore, analyses of clinical datasets revealed that the MALAT1 expression level was upregulated in OSCC compared to normal tissues, especially in the betel quid-chewing population. These results indicated involvement of MALAT1 SNPs rs3200401 and rs619586 in the development of OSCC and support the interaction between MALAT1 gene polymorphisms and the environmental carcinogen as a predisposing factor for OSCC progression.

Systems genetics analysis of oral squamous cell carcinoma susceptibility using the mouse model: current position and new perspective.

Oral squamous cell carcinoma (OSCC) is one of the most common human malignancies with complex etiology and poor prognosis. Although environmental carcinogens and carcinogenic viruses are still considered the main etiologic factors for OSCC development, genetic factors obviously play a key role in the initiation and progression of this neoplasm, given that not all individuals exposed to carcinogens develop the same severity of the disease, if any. Identifying genetic loci modulating OSCC risk may have several important clinical implications, including early detection, prevention and developing new treatment strategies. Due to limitations in controlled and standardized genetic studies in humans, genetic components underlying susceptibility of OSCC development remain largely unknown. A combination of quantitative trait loci mapping in mice, with complementary association studies in humans, has the potential to discover novel cancer risk loci. As of today, a limited number of genetic analyses were applied on rodent models to locate novel genetic loci associated with human OSCC. Here, we discuss the current status of the mouse models use for dissecting the genetic basis of OSCC and highlight how systems genetics analysis using mouse models, may increase our understanding of human OSCC susceptibility.

Cyclin D1 and p21 gene variants and oral squamous cell carcinoma risk and prognosis

Cyclin-dependent kinase inhibitor p21 (encoded by the CDKN1A gene) and cyclin D1 (encoded by the CCND1 gene) are important regulators of cell cycle progression and could have important effects in the complex process of neoplastic transformation. The current study aimed to investigate variants in CDKN1A (rs1801270, rs1059234) and CCND1 (rs9344) genes as potential risk and prognostic factors in oral squamous cell carcinoma (OSCC) patients. The study included 104 OSCC patients and 107 healthy individuals without a history of cancer. Genotypes were assessed by real-time PCR and TaqMan SNP genotyping. Significant differences in genotype distribution between OSCC cases and the control group were observed for the CCND1 rs9344 variant (p=0.017). According to the odds ratio (OR), adjusted for age and sex, the rs9344 heterozygous GA and homozygous mutated AA genotypes were associated with an increased OSCC susceptibility (OR=2.295, p=0.007; OR=2.029, p=0.037, respectively). Variants rs1801270 and rs105923 in CDKN1A were not associated with OSCC risk. There were no differences in overall survival among OSCC patients stratified by genotypes of the analyzed variants in CDKN1A and CCND1. Variant rs9344 in the CCND1 gene might be considered as a potential molecular risk factor for OSCC susceptibility but not for disease prognosis.

TRIM21 Polymorphisms are associated with Susceptibility and Clinical Status of Oral Squamous Cell Carcinoma patients.

Squamous cell cancer of head and neck (HNSCC) is the sixth most common malignancy worldwide. One of the most common HNSCC types is oral squamous cell carcinoma (OSCC), which is the fifth leading cause of cancer death in Taiwan. Tripartite motif 21 (TRIM21) has been reported to play an important role in different cancer types. We found a correlation between TRIM21 and survival of HNSCC patients, but little information exists about how altered TRIM21 expression contributes to tumorigenesis. Thus, we investigated the combined effect of TRIM21 polymorphisms and exposure to environmental carcinogens on the susceptibility and clinicopathological characteristics of OSCC. Two single-nucleotide polymorphisms (SNPs) of TRIM21 (rs4144331, rs915956) from 1194 healthy controls and 1192 OSCC patients were analyzed by real-time PCR. Among 1632 smokers, TRIM21 polymorphism carriers with the betel-nut chewing habit had a ~4.8-fold greater risk of OSCC than TRIM21 wild-type carriers without the betel-nut chewing habit. After adjusting for other covariants, OSCC patients with G/T at TRIM21 rs4144331 had a high risk for distant metastasis compared with G/G homozygotes. This study is the first to examine the risk factors associated with TRIM21 SNPs in OSCC progression and development. Thus, our findings suggest that this study is the first to examine the risk factors associated with TRIM21 SNPs in OSCC progression and development and suggest that interactions between mutant genes may alter the susceptibility to OSCC.

Impact of ERCC2 Gene Polymorphisms on OSCC Susceptibility and Clinical Characteristics.

Background DNA repair systems play an important role in maintaining the integrity of the human genome. Deficiency in the repair capacity due to either mutations or inherited polymorphisms in DNA repair genes may contribute to variations in the DNA repair capacity and subsequently susceptibility to cancer. Objectives This study aimed to investigate the association between Excision repair cross-complementation groups 2 (ERCC2) single nucleotide polymorphisms (SNPs rs1799793 and rs13181) and the response to platinum-based chemotherapy among patients with oral squamous cell carcinoma (OSCC). Methodology Polymerase chain reaction‐based restriction fragment length polymorphism analysis was used to determine the polymorphism from a total of 150 OSCC patients and 150 normal tissues of same patients were collected as controls for this study. Results ERCC2 GA (Asp312Asn) AC (Lys751Gln) genotypes were significantly associated ( p = 0.0001 and p = 0.0004, respectively) with OSCC patients, when compared with the controls. These findings suggest that potentially functional SNPs in ERCC2 may contribute to OSCC risk. This study highlights the genetic variant that might play a role in mediating susceptibility to OSCC in this population. An understanding of DNA repair gene polymorphisms might not only enable risk assessment, but also response to therapy, which target the DNA repair pathway.

The LncRNA H19 rs217727 Polymorphism Is Associated with Oral Squamous Cell Carcinoma Susceptibility in Iranian Population.

Lack of protein-coding capacity is a main characteristic of long noncoding RNAs (lncRNAs) which, as molecular biomarkers, have found a novel pharmacological application in cancer and are reported to be important regulators of gene expression. H19 is reportedly involved in cancer progression and tumorigenesis. One of the most common types of head and neck cancers is oral squamous cell carcinoma (OSCC). The main objective of the present study was to evaluate the correlation of OSCC susceptibility with H19 gene in an Iranian population. This research was performed on 400 subjects of both sexes referred to the Namazi Hospital affiliated with the Shiraz University of Medical Sciences (SUMS). Individuals aged 15-88 years were divided into two groups: pathologically diagnosed patients with new-onset OSCC and healthy controls. After written and informed consent was obtained from the individuals, genomic DNA was extracted. The tetra-primer ARMS-PCR technique was performed for DNA genotyping by the use of specific primer pairs. The susceptibility of OSCC and H19 gene polymorphism sites was further analyzed (rs217727 and rs2107425). The allele and genotype frequencies of H19 rs2107425 polymorphism were similar between OSCC cases and controls. The H19 rs217727T allele frequency was significantly higher in OSCC cases (P = 0.002), and the polymorphism of H19 rs217727 was associated with OSCC susceptibility in the codominant (OR = 6.04, 95%CI = 1.70 − 21.42, P = 0.001 for TT genotype), dominant (OR = 1.62, 95%CI = 1.08 − 2.43, P = 0.01), and recessive (OR = 5.32, 95%CI = 1.51 − 18.69, P = 0.003) models. This study showed that rs217727 and OSCC susceptibility were statistically correlated in the Iranian population.

Role of EGFR gene polymorphisms in oral squamous cell carcinoma patients of Southeast Iran: A case-control study.

Background:The decisive etiology of oral squamous cell carcinoma (OSCC) is still ambiguous, but we recognize the contribution of genetic aberration and environmental agents due to OSCC initiation. In the current study, we elucidate the potential impact of EGFR gene polymorphisms on the risk of OSCC in Southeast Iran.Methods:Forty-eight OSCC patients along with 100 healthy volunteers were included. Three polymorphisms of the EGFR gene (rs2227983, rs2293347 and rs2227984) were genotype by Tetra-ARMS PCR. Data were analyzed with a chi-square test, and p<0.05 was considered significant.Results:In rs2227983, the frequency of AG and GG genotypes were 62.5%, 37.5% in cases and 42%, 57% in the control group (P=0.02, OR=2.3) and also A allele frequency was 31.3% in the case and 22% in control (P=0.08, OR=0.62). AG + AA genotype frequency was 62.5% and 43% in case and control, respectively (p=0.03, OR=2.2). In rs2227984 and rs2293347, no statistical differences showed in the distribution of genotypes between the case and control group. Also the majority of the OSCC belonged to grade I (43.8%).Conclusion:The present investigation indicated that rs2227983 polymorphism might contribute to OSCC susceptibility in Iran's southeast population. Although, with the inconsistent interpretation mentioned due to the various geographical residencies and populations, more studies of significant populations are suggested to validate our findings.

Association of Interleukin-10 Genotypes and Oral Cancer Susceptibility in Selected Malaysian Population: A Case- Control Study

Background:Interleukin-10 (IL10) genotypes have been closely correlated to the susceptibility for oral squamous cell carcinoma. More than half of oral cancers in the world occur in Asia with estimated 168,850 new cases were diagnosed in this geographical region alone. Considering the rising numbers of oral cancer cases in Malaysia, association of IL10 A1082G gene polymorphism was correlated.Methodology:41 oral squamous cell carcinoma (OSCC) cases and 48 healthy controls of comparable age, gender, and with habits like smoking, alcohol consumption and betel quid chewing were selected. In this case-control study, samples were collected from the Oral Cancer Research and Coordinating Centre (OCRCC), Faculty of Dentistry, University of Malaya, Malaysia. Genotyping conditions were evaluated by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The PCR products were subjected to digestion by MnlI enzyme (NEB, UK) to screen for the IL10 A-1082G. Digested DNA products were analyzed by electrophoresis on 4% (w/v) agarose gel, stained with ethidium bromide and imaged under UV illumination. Chi-square test and Fisher’s Exact test were used in statistical analysis.Results:AG genotypes were present in 81.3% and 86.0% of healthy control and OSCC cases respectively (OR=0.468, 95% CI=0.133-1.653). No significant association was found between IL10 A1082G polymorphism with risk habits, clinico-pathological parameters and 5-years overall survival. The findings also show no significant correlation between the IL10 genotype and features of OSCC within the case group as measured by tumor size, lymph node involvement, stage, invasive front, grading, depth, pattern of invasion.Conclusion:This study suggests that functional polymorphism AG of IL10 A1082G may have no influence with OSCC susceptibility. However, further investigation with larger sample sizes can be conducted to provide additional evidence to support the lack of association of IL10 A1082G polymorphism in oral cancer.

Association of Resistin Gene Polymorphisms with Oral Squamous Cell Carcinoma Progression and Development.

Oral squamous cell carcinoma (OSCC) accounts for over 90% of malignant neoplasms of the mouth. In Taiwan, OSCC is the fourth most common male cancer and the fourth leading cause of male cancer death. Resistin (RETN) is an adipokine that is associated with obesity, inflammation, and various cancers. Here, we examine the association between four single nucleotide polymorphisms (SNPs) of the RETN gene (rs3745367, rs7408174, rs1862513, and rs3219175) and OSCC susceptibility as well as clinical outcomes in 935 patients with OSCC and in 1200 cancer-free healthy controls. We found that, in 1465 smokers, RETN polymorphisms carriers with the betel-nut chewing habit had a 6.708–10.882-fold greater risk of having OSCC compared to RETN wild-type carriers without the betel-nut chewing habit. Patients with OSCC who had A/A homozygous of RETN rs3219175 polymorphism showed a high risk for an advanced tumor size (> T2), compared to those patients with G/G homozygotes. In addition, A/T/G/G haplotype significantly increased the risks for OSCC by 1.376-fold. This study is the first to examine the risk factors associated with RETN SNPs in OSCC progression and development in Taiwan.

Human leucocyte antigen-G 14-bp InDel polymorphism and oral squamous cell carcinoma risk in Chinese Han population: A case-control study.

Human leucocyte antigen-G (HLA-G) is a nonclassical HLA class I molecule involved in tumour immune escape. The purpose of this study was to investigate the association between the 14-bp insertion/deletion (InDel) polymorphism in the 3' untranslated region (3'-UTR) of HLA-G gene and oral squamous cell carcinoma (OSCC) risk in Chinese Han population (216 cases and 193 healthy controls), and furthermore, to evaluate serum soluble HLA-G (sHLA-G) levels in the OSCC patients. Our results demonstrated that the Ins allele was significantly less frequent in the OSCC patients than that in the healthy controls (odds ratio [OR]=0.75; 95% confidence interval [CI]: 0.57-0.99; p=0.040). Distribution of the 14-bp genotypes in the OSCC patients and the healthy controls revealed that the Ins/Ins genotype was associated with decreased OSCC risk in both the codominant model (Ins/Ins versus Del/Del; OR=0.57; 95% CI=0.33-0.99; p=0.044) and the log-additive model (OR=0.76; 95% CI: 0.58-0.99; p=0.044). The serum sHLA-G level was significantly higher in the OSCC patients than those in the healthy controls (p<0.001). Receiver operating characteristic (ROC) curve revealed the valuable diagnostic value of sHLA-G for OSCC detection, with an area under the ROC curve (AUC) of 0.891 (95% CI: 0.856-0.925, p<0.001). The OSCC patients with Ins/Ins genotype had lower serum sHLA-G levels than those with Ins/Del and Del/Del genotypes (p=0.015). Furthermore, serum sHLA-G levels were significantly increased with the increasing TNM stages of the OSCC patients (p=0.017). Our findings revealed that the HLA-G 14-bp InDel polymorphism might be a genetic risk factor for OSCC susceptibility, and the serum sHLA-G may act as a promising biomarker for noninvasive diagnosis of OSCC.

A TGF-β1 genetic variant at the miRNA187 binding site significantly modifies risk of HPV16-associated oropharyngeal cancer.

TGF-β1rs1982073 polymorphism at the miRNA-187 binding site may alter TGF-β1 expression and function, and thereby this polymorphism (genotype CT/CC) increases cancer susceptibility. HPV16 L1 seropositivity is associated with the risk of oral squamous cell carcinoma (OSCC), including oropharyngeal squamous cell carcinoma (OPSCC) and oral cavity squamous cell carcinoma (OCSCC). Thus, we hypothesized that TGF-β1rs1982073 polymorphism at the miRNA-187 binding site combined with HPV16 L1 seropositivity may have a joint effect on OSCC susceptibility. We determined the genotypes of TGF-β1rs1982073 and HPV16 status in 325 OSCC subjects and 335 cancer-free controls in the non-Hispanic white population, and used logistic regression models to evaluate the joint effects on OSCC susceptibility. TGF-β1rs1982073 polymorphism (CT/CC genotype) combined with HPV16 L1 seropositivity increased the risk of OSCC via joint effects, particularly in OPSCC subjects who were never-smokers (OR, 165.9; 95% CI, 28.6-960.4) or never-drinkers (OR, 196.0; 95% CI, 28.2-1,000.0), respectively. Younger subjects had a higher risk of OPSCC than older subjects (OR, 23.5; 95% CI, 6.3-87.0 vs. OR, 6.0; 95% CI, 1.7-17.9, respectively). The significant associations between this polymorphism and HPV16-associated OSCC and OPSCC were also observed. However, OCSCC subjects did not have similar results. Our findings suggest that the joint effects of TGF-β1rs1982073 and HPV16 L1 seropositivity can increase risk of HPV16-associated oral cancer, particularly in OPSCC subjects who are never-smokers, never-drinkers and young. This result may help us understand the tumorigenesis process and improve early detection, which are critical for prevention and intervention strategies. However, larger studies are needed to validate our findings.

Correlation between prostate stem cell antigen gene expression and oral squamous cell carcinoma.

The aetiology of oral squamous cell carcinoma (OSCC) remains unclear. Numerous single nucleotide polymorphisms (SNPs) associated with cancer have been identified using genome-wide association studies (GWAS). The present study was designed to identify common SNPs associated with cancer susceptibility and to evaluate their involvement in OSCC. Susceptible loci were identified by analysing a cancer GWAS catalogue. A multicentre case-control study using an OSCC and control population was performed for selected SNPs. The function of the selected locus and its associated gene was explored using a reverse transcription-polymerase chain reaction, enzyme linked immunosorbent assay and immunohistochemistry. The association between genotypes and clinical parameters was assessed in 76 patients with OSCC. Rs2294008 located in the prostate stem cell antigen gene (PSCA) was selected. It was identified that the rs2294008 polymorphism was associated with OSCC susceptibility and PSCA may be involved in the development, progression and prognosis of OSCC.

Association of toll-like receptors with the risk of oral squamous cell carcinoma.

Association of toll-like receptors (TLRs) with the risk of oral squamous cell carcinoma (OSCC) from the published reports is still conflicting. This study was conducted to evaluate the relationship between TLRs and the risk of OSCC using meta-analysis method. The association studies were identified from PubMed and Cochrane Library on April 01 2015, and eligible investigations were included and synthesized using meta-analysis method. Three reports were recruited into this meta-analysis for the association of TLRs with OSCC susceptibility. In this meta-analysis, we found that TLRs were not associated with OSCC susceptibility. However, in the sub-group analysis, we found that TLR-7 was associated with OSCC risk. TLR-7 was associated with OSCC risk. TLR-7 might be an indicator to predict the OSCC risk. However, more studies should be conducted to confirm it.

Functional FGFR4 Gly388Arg polymorphism contributes to oral squamous cell carcinoma susceptibility.

Aberrations of the fibroblast growth factor receptor 4 (FGFR4) genomic region include amplification of FGFR4, activation of FGFR4 kinase domain mutations, and overexpression of FGFR4, which lead to sustained cell proliferation and contribute to tumor development. However, the association between FGFR4 single-nucleotide polymorphisms (SNPs) and risk of oral squamous cell carcinoma (OSCC) remains to be determined. We investigated the relationships between FGFR4 genetic polymorphisms, OSCC development and clinicopathological variables. We recruited a total of 955 patients with OSCC and 1191 controls. Four SNPs of FGFR4 (rs2011077, rs351855, rs7708357, and rs1966265) were examined using real-time polymerase chain reaction. We found that with the rs351855 GA genotype and a combination of the GA and AA genotypes exhibited a 1.431-fold (95% CI: 1.092-1.876) and 1.335-fold (95% CI: 1.033-1.725) higher risk of OSCC. However, patients with OSCC with a homozygous A/A genotype of FGFR4 rs351855 polymorphism had a lower risk of advanced stage OSCC (P = 0.0252). Furthermore, the patients with the FGFR4 rs351855/rs1966265 A-A haplotype had a 2.890-fold (95% confidence interval [CI]: 2.257–3.700) higher risk of OSCC than the controls. Betel quid chewers with the A-A haplotype had a considerably higher risk (95% CI: 16.159–26.937) of OSCC than did betel quid nonchewers with other haplotypes. Moreover, an additional integrated in silico analysis proposed that rs351855 G allele variant to the A allele exhibited a relatively low energy of the transmembrane region. In conclusion, our results suggest that the FGFR4 rs351855 may play a role in susceptibility for OSCC development.

MiRNA genetic variants: As potential diagnostic biomarkers for oral cancer

MicroRNAs (miRNAs) comprise a novel class of small, non-coding endogenous RNAs that have a role in the plethora of regulatory activities by directing their target mRNAs for degradation or translational repression. Single nucleotide polymorphisms (SNPs) in miRNA genes can lead to alteration in mRNA expression, resulting in serious consequences. Detection of miRNA-polymorphisms can potentially improve diagnosis, treatment, prognosis in patients and has extreme implications in the fields of pharmacogenomics and personalization of medicine. The aim of this study is to investigate the association between miR-499 A/G and miR-149 C/T polymorphisms with susceptibility to development of Oral Squamous Cell Carcinoma (OSCC). 200 histopathologically diagnosed and confirmed samples from OSCC patients and 200 control samples from the general population were recruited for the study. All OSCC patients were graded based on their differentiation, and genetic analysis was performed by PCR-RFLP and sequencing. qRT-PCR was carried out to compare the expression of miR-499 and miR-149 in different grades of various stages of OSCC patients concerning to the controls. Further Immunohistochemistry (IHC) was performed to study the target gene of miR-499. The study shows a probable association of miR-499 A/G and miR-149 C/T with susceptibility of OSCC. Random sequencing analysis and Immunohistochemistry contribute to the result that miR-499 A/G increases the susceptibility of OSCC by targeting SOX-6. PCR- Restriction Fragment Length Polymorphism (RFLP) and multivariable logistic analysis revealed that there is a significant association between miR-149 CT+TT and CT and susceptibility of OSCC. Our study suggests that miR-499 A/G and miR-149 C/T polymorphisms may play crucial roles in susceptibility and development of OSCC in Indian population.

Effect of genetic variation in microRNA binding site in WNT1-inducible signaling pathway protein 1 gene on oral squamous cell carcinoma susceptibility.

BackgroundOral squamous cell carcinoma (OSCC), which is the most common head and neck cancer, accounts for 1%–2% of all human malignancies and is characterized by poor prognosis and reduced survival rates. WNT1-inducible signaling pathway protein 1 (WISP1), a cysteine-rich protein belonging to the Cyr61, CTGF, Nov (CCN) family of matricellular proteins, has many developmental functions and may be involved in carcinogenesis. This study investigated WISP1 single-nucleotide polymorphisms (SNPs) to elucidate OSCC susceptibility and clinicopathologic characteristics.Methodology/Principal findingsReal-time polymerase chain reaction was used to analyze 6 SNPs of WISP1 in 900 OSCC patients and 1200 cancer-free controls. The results showed that WISP1 rs2929970 polymorphism carriers with at least one G allele were susceptible to OSCC. Moreover, compared with smokers, non-smoker patients with higher frequencies of WISP1 rs2929970 (AG + GG) variants had a late stage (stages III and IV) and a large tumor size. In addition, OSCC patients who were betel quid chewers and carried WISP1 rs16893344 (CT + TT) variants had a low risk of lymph node metastasis.ConclusionOur results demonstrate that a joint effect of WISP1 rs2929970 with smoking as well as WISP1 rs16893344 with betel nut chewing causally contributes to the occurrence of OSCC. WISP1 polymorphism may serve as a marker or a therapeutic target in OSCC.