Information:
Error:
ID
45269
Description
Principal Investigator: Zhiheng Pei, MD, PhD, NYU Langone Medical Center, New York, NY, USA MeSH: Esophageal Adenocarcinoma,Barrett's Esophagus,GERD https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000260 The distal esophagus is an important anatomical area where gastric acid reflux can cause reflux esophagitis (RE), Barrett's esophagus (BE) (intestinal metaplasia), and esophageal adenocarcinoma (EA). The incidence of EA has increased 6-fold in the U.S. since the 1970s, parallel to a significant increase in the prevalence of gastroesophageal reflux diseases (GERD). Although specific host factors might predispose one to disease risk, such a rapid increase in incidence must be predominantly environmental. The cause remains unknown. Our hypothesis is that changes in the foregut microbiome are associated with EA and its precursors, RE and BE in the GERD sequence. We will conduct a case control study to characterize the microbiome in every stage of the GERD sequence as well as analyze the trend in changes in the microbiome along disease progression toward EA. Specific Aim 1. To conduct a comprehensive population survey of the foregut microbiome and demonstrate its association with GERD sequence, by a 16S rRNA gene survey. We will analyze samples of the foregut microbiome at three anatomic loci: mouth, distal esophagus, and gastric corpus. Changes of the microbiota in the distal esophagus will be correlated with the phenotypes. Spatial relationship between the esophageal microbiota and upstream (mouth) and downstream (stomach) foregut microbiotas as well as temporal stability of the microbiome-disease association will also be examined. Specific Aim 2. To define distal esophageal metagenome and demonstrate its association with GERD sequence, by shotgun metagenomic analysis. We will first classify samples of the metagenome into metagenotypes by between-sample k-mer distance and correlate the metagenotypes with the four phenotypes. Subsequent detailed analyses will include pathway-disease and gene-disease associations. DNA viruses and fungi, if identified, also will be correlated with the phenotypes. A significant association between the foregut microbiome composition and GERD sequence, if demonstrated, will be the first step for eventually testing the causal hypothesis that an abnormal microbiome is required for the development of the sequence of phenotypic changes toward EA. If EA and its precursors represent a microbial ecological disease, treating the cause of GERD might become possible, for example, by normalizing the microbiome through use of antibiotics, probiotics, or prebiotics. Causative therapy for GERD could prevent its progression and reverse the current trend of increasing incidence of EA.
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Keywords
Versions (2)
- 6/7/22 6/7/22 - Dr. Christian Niklas
- 10/12/22 10/12/22 - Adrian Schulz
Copyright Holder
Zhiheng Pei, MD, PhD
Uploaded on
October 12, 2022
DOI
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License
Creative Commons BY 4.0
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dbGaP phs000260 Foregut Microbiome in Development of Esophageal Adenocarcinoma
Eligibility Criteria
- StudyEvent: SEV1
- Eligibility Criteria
- This subject consent data table contains subject IDs and consent group information.
- This subject sample mapping data table includes a mapping of study subject IDs to sample IDs. Samples are the final preps submitted for genotyping, sequencing, and/or expression data. For example, if one patient (subject ID) gave one sample, and that sample was processed differently to generate 2 sequencing runs, there would be two rows, both using the same subject ID, but having 2 unique sample IDs. The data table also includes sample use.
- This subject phenotype data table includes collection of subject sociodemography (n=5 variables; country of birth, age at first visit, gender, race, hispanic origin), diagnosis and phenotype, specifically, whether subject is normal, has reflux esophagitis, Barrett's esophagus, or esophageal adenocarcinoma.
- This sample attributes data table includes body site, analyte type, tumor status, visit number and date, and sequencing center.
Similar models
Eligibility Criteria
- StudyEvent: SEV1
- Eligibility Criteria
- This subject consent data table contains subject IDs and consent group information.
- This subject sample mapping data table includes a mapping of study subject IDs to sample IDs. Samples are the final preps submitted for genotyping, sequencing, and/or expression data. For example, if one patient (subject ID) gave one sample, and that sample was processed differently to generate 2 sequencing runs, there would be two rows, both using the same subject ID, but having 2 unique sample IDs. The data table also includes sample use.
- This subject phenotype data table includes collection of subject sociodemography (n=5 variables; country of birth, age at first visit, gender, race, hispanic origin), diagnosis and phenotype, specifically, whether subject is normal, has reflux esophagitis, Barrett's esophagus, or esophageal adenocarcinoma.
- This sample attributes data table includes body site, analyte type, tumor status, visit number and date, and sequencing center.
Name
Type
Description | Question | Decode (Coded Value)
Data type
Alias
Item Group
Inclusion and exclusion criteria
C1512693 (UMLS CUI [1,1])
C0680251 (UMLS CUI [1,2])
C0680251 (UMLS CUI [1,2])
Item
*Inclusion Criteria:* Subjects will be screened by questionnaire with or without heartburn symptom, endoscopic examination, histological examination, and 48-hour pH monitoring. A subject will be considered for enrollment into this study if the results of his/her screening examinations are diagnostic for one of the following four phenotypes:
text
C1512693 (UMLS CUI [1,1])
C0220908 (UMLS CUI [1,2])
C0034394 (UMLS CUI [1,3])
C0332288 (UMLS CUI [1,4])
C0018834 (UMLS CUI [1,5])
C0014245 (UMLS CUI [1,6])
C0019638 (UMLS CUI [1,7])
C0202165 (UMLS CUI [1,8])
C0220908 (UMLS CUI [1,2])
C0034394 (UMLS CUI [1,3])
C0332288 (UMLS CUI [1,4])
C0018834 (UMLS CUI [1,5])
C0014245 (UMLS CUI [1,6])
C0019638 (UMLS CUI [1,7])
C0202165 (UMLS CUI [1,8])
Code List
*Inclusion Criteria:* Subjects will be screened by questionnaire with or without heartburn symptom, endoscopic examination, histological examination, and 48-hour pH monitoring. A subject will be considered for enrollment into this study if the results of his/her screening examinations are diagnostic for one of the following four phenotypes:
CL Item
No (0)
CL Item
Yes (1)
CL Item
No answer (2)
Item
*Normal control:* Normal control will be selected from subjects who present to the GI Clinics. The normal control should meet all of the following four criteria: 1) no reflux symptoms, such as heart burn; 2) normal endoscopic findings; 3) histopathological examination shows no inflammatory infiltrate or less than 10 lymphocytes per high power field (HPF, 400x magnification) in the squamous epithelium; 4) normal pH range (the fraction time of pH < 4 and DeMeester score < 14.72) with 48-hour pH monitoring test. Besides the classic normal phenotype, there are two variants. *Perinormal:* subjects meet all the normal control criteria but pathological examination was not performed because gastroenterologists decided there was no indication to take biopsies based on the EGD findings. *Treated Normal:* Subjects meet all the normal control criteria but are have been treated recently with PPI or antacid.
text
C0009932 (UMLS CUI [1,1])
C1298908 (UMLS CUI [1,2])
C0017168 (UMLS CUI [1,3])
C0205307 (UMLS CUI [1,4])
C0014245 (UMLS CUI [1,5])
C0019638 (UMLS CUI [1,6])
C1298908 (UMLS CUI [1,7])
C0021368 (UMLS CUI [1,8])
C0205307 (UMLS CUI [1,9])
C0202165 (UMLS CUI [1,10])
C0009932 (UMLS CUI [2,1])
C1298908 (UMLS CUI [2,2])
C0005558 (UMLS CUI [2,3])
C0087111 (UMLS CUI [3,1])
C0358591 (UMLS CUI [3,2])
C1298908 (UMLS CUI [1,2])
C0017168 (UMLS CUI [1,3])
C0205307 (UMLS CUI [1,4])
C0014245 (UMLS CUI [1,5])
C0019638 (UMLS CUI [1,6])
C1298908 (UMLS CUI [1,7])
C0021368 (UMLS CUI [1,8])
C0205307 (UMLS CUI [1,9])
C0202165 (UMLS CUI [1,10])
C0009932 (UMLS CUI [2,1])
C1298908 (UMLS CUI [2,2])
C0005558 (UMLS CUI [2,3])
C0087111 (UMLS CUI [3,1])
C0358591 (UMLS CUI [3,2])
Code List
*Normal control:* Normal control will be selected from subjects who present to the GI Clinics. The normal control should meet all of the following four criteria: 1) no reflux symptoms, such as heart burn; 2) normal endoscopic findings; 3) histopathological examination shows no inflammatory infiltrate or less than 10 lymphocytes per high power field (HPF, 400x magnification) in the squamous epithelium; 4) normal pH range (the fraction time of pH < 4 and DeMeester score < 14.72) with 48-hour pH monitoring test. Besides the classic normal phenotype, there are two variants. *Perinormal:* subjects meet all the normal control criteria but pathological examination was not performed because gastroenterologists decided there was no indication to take biopsies based on the EGD findings. *Treated Normal:* Subjects meet all the normal control criteria but are have been treated recently with PPI or antacid.
CL Item
No (0)
CL Item
Yes (1)
CL Item
No answer (2)
Item
*Reflux esophagitis (RE):* Subjects should meet all of the following four criteria: 1) reflux symptoms, such as heart burn; 2) endoscopic esophagitis, classified to Grade A, B, C, and D according Los Angeles Classification of reflux esophagitis; 3) histopathological esophagitis, characterized by basal zone hyperplasia exceeding 20% of the epithelial thickness, papillae extending into the superficial third of the epithelium, and presence of lymphocytes equal to or more than 10 cells/HPF or any numbers of eosinophils or polymorphonuclear leukocytes; 4) evidence of gastric reflux, determined by 48-hour pH monitoring test, abnormal Brovo pH monitoring with the fraction time of pH > 4% and DeMeester score > 14.72. Besides the classic reflux esophagitis phenotype, there are two variants. *Partial esophagitis:* these patients have reflux symptoms and abnormal pH test results but either EGD or pathology but not both shows evidence of esophagitis. *No-esophagitis (NERD):* these patients have reflux symptoms and abnormal pH test results but both EGD and pathology show no evidence of esophagitis.
text
C0017168 (UMLS CUI [1,1])
C0018834 (UMLS CUI [1,2])
C0014868 (UMLS CUI [1,3])
C0014245 (UMLS CUI [1,4])
C0019638 (UMLS CUI [1,5])
C0205161 (UMLS CUI [1,6])
C0202165 (UMLS CUI [1,7])
C1881447 (UMLS CUI [1,8])
C1883701 (UMLS CUI [1,9])
C1881342 (UMLS CUI [1,10])
C1881343 (UMLS CUI [1,11])
C1881344 (UMLS CUI [1,12])
C0017168 (UMLS CUI [2,1])
C0205161 (UMLS CUI [2,2])
C0202165 (UMLS CUI [2,3])
C1521733 (UMLS CUI [2,4])
C0014245 (UMLS CUI [2,5])
C0332288 (UMLS CUI [2,6])
C0019638 (UMLS CUI [2,7])
C0017168 (UMLS CUI [3,1])
C0019638 (UMLS CUI [3,2])
C0205161 (UMLS CUI [3,3])
C0202165 (UMLS CUI [3,4])
C0332288 (UMLS CUI [3,5])
C1521733 (UMLS CUI [3,6])
C0014245 (UMLS CUI [3,7])
C0019638 (UMLS CUI [3,8])
C0018834 (UMLS CUI [1,2])
C0014868 (UMLS CUI [1,3])
C0014245 (UMLS CUI [1,4])
C0019638 (UMLS CUI [1,5])
C0205161 (UMLS CUI [1,6])
C0202165 (UMLS CUI [1,7])
C1881447 (UMLS CUI [1,8])
C1883701 (UMLS CUI [1,9])
C1881342 (UMLS CUI [1,10])
C1881343 (UMLS CUI [1,11])
C1881344 (UMLS CUI [1,12])
C0017168 (UMLS CUI [2,1])
C0205161 (UMLS CUI [2,2])
C0202165 (UMLS CUI [2,3])
C1521733 (UMLS CUI [2,4])
C0014245 (UMLS CUI [2,5])
C0332288 (UMLS CUI [2,6])
C0019638 (UMLS CUI [2,7])
C0017168 (UMLS CUI [3,1])
C0019638 (UMLS CUI [3,2])
C0205161 (UMLS CUI [3,3])
C0202165 (UMLS CUI [3,4])
C0332288 (UMLS CUI [3,5])
C1521733 (UMLS CUI [3,6])
C0014245 (UMLS CUI [3,7])
C0019638 (UMLS CUI [3,8])
Code List
*Reflux esophagitis (RE):* Subjects should meet all of the following four criteria: 1) reflux symptoms, such as heart burn; 2) endoscopic esophagitis, classified to Grade A, B, C, and D according Los Angeles Classification of reflux esophagitis; 3) histopathological esophagitis, characterized by basal zone hyperplasia exceeding 20% of the epithelial thickness, papillae extending into the superficial third of the epithelium, and presence of lymphocytes equal to or more than 10 cells/HPF or any numbers of eosinophils or polymorphonuclear leukocytes; 4) evidence of gastric reflux, determined by 48-hour pH monitoring test, abnormal Brovo pH monitoring with the fraction time of pH > 4% and DeMeester score > 14.72. Besides the classic reflux esophagitis phenotype, there are two variants. *Partial esophagitis:* these patients have reflux symptoms and abnormal pH test results but either EGD or pathology but not both shows evidence of esophagitis. *No-esophagitis (NERD):* these patients have reflux symptoms and abnormal pH test results but both EGD and pathology show no evidence of esophagitis.
CL Item
No (0)
CL Item
Yes (1)
CL Item
No answer (2)
Item
*Barrett's esophagus (BE):* esophageal squamous epithelium replaced by intestinal-type epithelial cells and goblet cells. BE is categorized as either long-segment (BE-L) or short-segment disease (BE-S): BE-L affects 3 cm or more of the esophagus while BE-S affects less than 3 cm of the esophagus.
text
C1333324 (UMLS CUI [1,1])
Code List
*Barrett's esophagus (BE):* esophageal squamous epithelium replaced by intestinal-type epithelial cells and goblet cells. BE is categorized as either long-segment (BE-L) or short-segment disease (BE-S): BE-L affects 3 cm or more of the esophagus while BE-S affects less than 3 cm of the esophagus.
CL Item
No (0)
CL Item
Yes (1)
CL Item
No answer (2)
Item
*Esophageal Adenocarcinoma (EA):* atypical intestinal-type glands with high grade dysplasia. There are two subphenotypes: 1) adenocarcinoma *in situ*, defined by the absence of invasion of tumor cells through the basement membrane. 2) invasive adenocarcinoma, defined by the presence of invasion of tumor cells into the submucosa or below.
text
C1522619 (UMLS CUI [1,1])
C0001418 (UMLS CUI [1,2])
C0001418 (UMLS CUI [2,1])
C0007099 (UMLS CUI [2,2])
C0001418 (UMLS CUI [3,1])
C1334274 (UMLS CUI [3,2])
C0001418 (UMLS CUI [1,2])
C0001418 (UMLS CUI [2,1])
C0007099 (UMLS CUI [2,2])
C0001418 (UMLS CUI [3,1])
C1334274 (UMLS CUI [3,2])
Code List
*Esophageal Adenocarcinoma (EA):* atypical intestinal-type glands with high grade dysplasia. There are two subphenotypes: 1) adenocarcinoma *in situ*, defined by the absence of invasion of tumor cells through the basement membrane. 2) invasive adenocarcinoma, defined by the presence of invasion of tumor cells into the submucosa or below.
CL Item
No (0)
CL Item
Yes (1)
CL Item
No answer (2)
Item
The final decision on enrollment of a subject will be determined by frequency-match on gender, ethnic background, and age within 10 years.
text
C1708943 (UMLS CUI [1,1])
C0079399 (UMLS CUI [1,2])
C0015031 (UMLS CUI [1,3])
C0001779 (UMLS CUI [1,4])
C0079399 (UMLS CUI [1,2])
C0015031 (UMLS CUI [1,3])
C0001779 (UMLS CUI [1,4])
Code List
The final decision on enrollment of a subject will be determined by frequency-match on gender, ethnic background, and age within 10 years.
CL Item
No (0)
CL Item
Yes (1)
CL Item
No answer (2)
Elig.phs000260.v4.p2.7
Item
*Exclusion Criteria:*
text
C0680251 (UMLS CUI [1,1])
Item
Use of antibioics within 8 weeks before the scheduled endoscopic examination
text
C0205156 (UMLS CUI [1,1])
C1524063 (UMLS CUI [1,2])
C0003232 (UMLS CUI [1,3])
C1524063 (UMLS CUI [1,2])
C0003232 (UMLS CUI [1,3])
CL Item
No (0)
CL Item
Yes (1)
CL Item
No answer (2)
Item
Previous gastric/esophageal surgery
text
C0205156 (UMLS CUI [1,1])
C1522619 (UMLS CUI [1,2])
C0038351 (UMLS CUI [1,3])
C0543467 (UMLS CUI [1,4])
C1522619 (UMLS CUI [1,2])
C0038351 (UMLS CUI [1,3])
C0543467 (UMLS CUI [1,4])
CL Item
No (0)
CL Item
Yes (1)
CL Item
No answer (2)
Item
Active infection of the oral cavity
text
C0009450 (UMLS CUI [1,1])
C0226896 (UMLS CUI [1,2])
C0226896 (UMLS CUI [1,2])
CL Item
No (0)
CL Item
Yes (1)
CL Item
No answer (2)
Item
Active gastric ulcer disease or gastric cancer
text
C0205177 (UMLS CUI [1,1])
C0038358 (UMLS CUI [1,2])
C0699791 (UMLS CUI [1,3])
C0038358 (UMLS CUI [1,2])
C0699791 (UMLS CUI [1,3])
CL Item
No (0)
CL Item
Yes (1)
CL Item
No answer (2)
CL Item
No (0)
CL Item
Yes (1)
CL Item
No answer (2)
Item
Pregnant women, because the natural history of reflux disease in pregnancy is different from GERD in general populations that leads to metaplasia and/or dysplasia
text
C0032961 (UMLS CUI [1,1])
Code List
Pregnant women, because the natural history of reflux disease in pregnancy is different from GERD in general populations that leads to metaplasia and/or dysplasia
CL Item
No (0)
CL Item
Yes (1)
CL Item
No answer (2)
CL Item
No (0)
CL Item
Yes (1)
CL Item
No answer (2)
Item
For safety reasons, we wll exclude potential subjects with coagulopathy (INR > 2.0) or thrombocytopenia (platelet count < 50) since this study involves repeated mucosal sampling.
text
C0005779 (UMLS CUI [1,1])
C0040034 (UMLS CUI [1,2])
C0040034 (UMLS CUI [1,2])
Code List
For safety reasons, we wll exclude potential subjects with coagulopathy (INR > 2.0) or thrombocytopenia (platelet count < 50) since this study involves repeated mucosal sampling.
CL Item
No (0)
CL Item
Yes (1)
CL Item
No answer (2)
Item
Subjects at high risk for developing endocarditis, such as those with a history of endocarditis, rheumatic heart disease, or heart valve prosthesis who might require antibiotic prophylaxis for the endoscopic examination.
text
C0262926 (UMLS CUI [1,1])
C0014118 (UMLS CUI [1,2])
C0018825 (UMLS CUI [1,3])
C0035439 (UMLS CUI [1,4])
C0014118 (UMLS CUI [1,2])
C0018825 (UMLS CUI [1,3])
C0035439 (UMLS CUI [1,4])
Code List
Subjects at high risk for developing endocarditis, such as those with a history of endocarditis, rheumatic heart disease, or heart valve prosthesis who might require antibiotic prophylaxis for the endoscopic examination.
CL Item
No (0)
CL Item
Yes (1)
CL Item
No answer (2)
Item
Subjects with a history of intestinal ischemia and those with severe cardiopulmonary disease, or neurological impairment.
text
C0262926 (UMLS CUI [1,1])
C0853812 (UMLS CUI [1,2])
C0205082 (UMLS CUI [1,3])
C0553534 (UMLS CUI [1,4])
C3808195 (UMLS CUI [1,5])
C0205494 (UMLS CUI [1,6])
C0853812 (UMLS CUI [1,2])
C0205082 (UMLS CUI [1,3])
C0553534 (UMLS CUI [1,4])
C3808195 (UMLS CUI [1,5])
C0205494 (UMLS CUI [1,6])
Code List
Subjects with a history of intestinal ischemia and those with severe cardiopulmonary disease, or neurological impairment.
CL Item
No (0)
CL Item
Yes (1)
CL Item
No answer (2)
Item
Subject who has an imperforate anus, recent anal or rectal surgery.
text
C0003461 (UMLS CUI [1,1])
C0205052 (UMLS CUI [1,2])
C0543467 (UMLS CUI [1,3])
C0205052 (UMLS CUI [1,2])
C0543467 (UMLS CUI [1,3])
CL Item
No (0)
CL Item
Yes (1)
CL Item
No answer (2)
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