Dataset Information

Oral Microbiota and Risk for Esophageal Squamous Cell Carcinoma in a High-Risk Area of China.

ABSTRACT: Poor oral health has been linked with an increased risk of esophageal squamous cell carcinoma (ESCC). We investigated whether alteration of oral microbiota is associated with ESCC risk. Fasting saliva samples were collected from 87 incident and histopathologicallly diagnosed ESCC cases, 63 subjects with dysplasia and 85 healthy controls. All subjects were also interviewed with a questionnaire. V3-V4 region of 16S rRNA was amplified and sequenced by 454-pyrosequencing platform. Carriage of each genus was compared by means of multivariate-adjusted odds ratios derived from logistic regression model. Relative abundance was compared using Metastats method. Beta diversity was estimated using Unifrac and weighted Unifrac distances. Principal coordinate analysis (PCoA) was applied to ordinate dissimilarity matrices. Multinomial logistic regression was used to compare the coordinates between different groups. ESCC subjects had an overall decreased microbial diversity compared to control and dysplasia subjects (P<0.001). Decreased carriage of genera Lautropia, Bulleidia, Catonella, Corynebacterium, Moryella, Peptococcus and Cardiobacterium were found in ESCC subjects compared to non-ESCC subjects. Multinomial logistic regression analyses on PCoA coordinates also revealed that ESCC subjects had significantly different levels for several coordinates compared to non-ESCC subjects. In conclusion, we observed a correlation between altered salivary bacterial microbiota and ESCC risk. The results of our study on the saliva microbiome are of particular interest as it reflects the shift in microbial communities. Further studies are warranted to verify this finding, and if being verified, to explore the underlying mechanisms.

SUBMITTER: Chen X

PROVIDER: S-EPMC4671675 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Oral Microbiota and Risk for Esophageal Squamous Cell Carcinoma in a High-Risk Area of China.

Chen Xingdong X Winckler Björn B Lu Ming M Cheng Hongwei H Yuan Ziyu Z Yang Yajun Y Jin Li L Ye Weimin W

PloS one 20151207 12

Poor oral health has been linked with an increased risk of esophageal squamous cell carcinoma (ESCC). We investigated whether alteration of oral microbiota is associated with ESCC risk. Fasting saliva samples were collected from 87 incident and histopathologicallly diagnosed ESCC cases, 63 subjects with dysplasia and 85 healthy controls. All subjects were also interviewed with a questionnaire. V3-V4 region of 16S rRNA was amplified and sequenced by 454-pyrosequencing platform. Carriage of each g ...[more]

PMID: 26641451

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Project description:BackgroundThe human major histocompatibility complex (MHC) is the most important region in vertebrate genome, and is crucial in innate immunity. Recent studies have demonstrated the possible role of polymorphisms in the MHC region to high risk for esophageal squamous cell carcinoma (ESCC). Our previous genome-wide association study (GWAS) has indicated that the MHC region may confer important risk loci for ESCC, but without further fine mapping. The aim of this study is to further identify the risk loci in the MHC region for ESCC in Chinese population.MethodsConditional logistic regression analysis (CLRA) was performed on 24 single nucleotide polymorphisms (SNPs) within the MHC region, which were obtained from the genetically matched 937 cases and 692 controls of Chinese Han population. The identified promising SNPs were further correlated with clinical and clinicopathology characteristics. Immunohistochemistry was performed to explore the protein expression pattern of the related genes in ESCC and neighboring normal tissues.ResultsOf the 24 promising SNPs analyzed, we identified three independent SNPs in the MHC region associated with ESCC: rs35399661 (P = 6.07E-06, OR = 1.71, 95%CI = 1.36-2.17), rs3763338 (P = 1.62E-05, OR = 0.63, 95%CI = 0.50-0.78) and rs2844695 (P = 7.60E-05, OR = 0.74, 95%CI = 0.64-0.86). These three SNPs were located at the genes of HLA-DQA1, TRIM27, and DPCR1, respectively. Further analyses showed that rs2844695 was preferentially associated with younger ESCC cases (P = 0.009). The positive immunostaining rates both for HLA-DQA1 and TRIM27 were much higher in ESCC tissues than in neighboring normal tissues (69.4% vs. 26.8% for HLA-DQA1 and 77.6% vs. 47.8% for TRIM27, P<0.001). Furthermore, the overexpression of HLA-DQA1 is correlated significantly with age (P = 0.001) and family history (P<0.001).ConclusionThis study for the first time provides evidence that multiple genetic factors within the MHC region confer risk to ESCC on the subjects from high-risk area in northern China.

Project description:BackgroundEsophageal microbiota may influence esophageal squamous cell carcinoma (ESCC) pathobiology. Therefore, we investigated the characteristics and interplay of the esophageal microbiota in ESCC.MethodsWe performed 16S ribosomal RNA sequencing on paired esophageal tumor and tumor-adjacent samples obtained from 120 primarily ESCC patients. Analyses were performed using quantitative insights into microbial 2 (QIIME2) and phylogenetic investigation of communities by reconstruction of unobserved states 2 (PICRUSt2). Species found to be associated with ESCC were validated using quantitative PCR.ResultsThe microbial diversity and composition of ESCC tumor tissues significantly differed from tumor-adjacent tissues; this variation between subjects beta diversity is mainly explained by regions and sampling seasons. A total of 56 taxa were detected with differential abundance between the two groups, such as R. mucilaginosa, P. endodontalis, N. subflava, H. Pylori, A. Parahaemolyticus, and A. Rhizosphaerae. Quantitative PCR confirmed the enrichment of the species P. endodontalis and the reduction of H. Pylori in tumor-adjacent tissues. Compared with tumor tissue, a denser and more complex association network was formed in tumor-adjacent tissue. The above differential taxa, such as H. Pylori, an unclassified species in the genera Sphingomonas, Haemophilus, Phyllobacterium, and Campylobacter, also participated in both co-occurrence networks but played quite different roles. Most of the differentially abundant taxa in tumor-adjacent tissues were negatively associated with the epidermal growth factor receptor (EGFR), erb-b2 receptor tyrosine kinase 2 (ERBB2), erb-b2 receptor tyrosine kinase 4 (ERBB4), and fibroblast growth factor receptor 1 (FGFR1) signaling pathways, and positively associated with the MET proto-oncogene, receptor tyrosine kinase (MET) and phosphatase and tensin homolog (PTEN) signaling pathways in tumors.ConclusionAlterations in the microbial co-occurrence network and functional pathways in ESCC tissues may be involved in carcinogenesis and the maintenance of the local microenvironment for ESCC.

Dataset Information

Oral Microbiota and Risk for Esophageal Squamous Cell Carcinoma in a High-Risk Area of China.

Publications

Oral Microbiota and Risk for Esophageal Squamous Cell Carcinoma in a High-Risk Area of China.

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