Data from A Newly Identified Susceptibility Locus near <i>FOXP1</i> Modifies the Association of Gastroesophageal Reflux with Barrett's Esophagus
James Y. DaiJean de Dieu TapsobaMatthew F. BuasLynn OnstadDavid M. LevineHarvey A. RischWong‐Ho ChowLeslie BernsteinWeimin YeJesper LagergrenNigel C. BirdDouglas A. CorleyNicholas J. ShaheenAnna H. WuBrian J. ReidLaura J. HardieDavid C. WhitemanThomas L. Vaughan
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<div>Abstract<p><b>Background:</b> Important risk factors for esophageal adenocarcinoma and its precursor, Barrett's esophagus, include gastroesophageal reflux disease, obesity, and cigarette smoking. Recently, genome-wide association studies have identified seven germline single-nucleotide polymorphisms (SNP) that are associated with risk of Barrett's esophagus and esophageal adenocarcinoma. Whether these genetic susceptibility loci modify previously identified exposure–disease associations is unclear.</p><p><b>Methods:</b> We analyzed exposure and genotype data from the BEACON Consortium discovery phase GWAS, which included 1,516 esophageal adenocarcinoma case patients, 2,416 Barrett's esophagus case patients, and 2,187 control participants. We examined the seven newly identified susceptibility SNPs for interactions with body mass index, smoking status, and report of weekly heartburn or reflux. Logistic regression models were used to estimate ORs for these risk factors stratified by SNP genotype, separately for Barrett's esophagus and esophageal adenocarcinoma.</p><p><b>Results:</b> The odds ratio for Barrett's esophagus associated with at least weekly heartburn or reflux varied significantly with the presence of at least one minor allele of <i>rs2687201</i> (nominal <i>P</i> = 0.0005, FDR = 0.042). ORs (95% CIs) for weekly heartburn or reflux among participants with 0, 1, or 2 minor alleles of <i>rs2687201</i> were 6.17 (4.91–7.56), 3.56 (2.85–4.44), and 3.97 (2.47–6.37), respectively. No statistically significant interactions were observed for smoking status and body mass index.</p><p><b>Conclusion:</b> Reflux symptoms are more strongly associated with Barrett's esophagus risk among persons homozygous for the major allele of <i>rs2687201</i>, which lies approximately 75 kb downstream of the transcription factor gene <i>FOXP1</i>.</p><p><b>Impact:</b> The novel gene–exposure interaction discovered in this study provides new insights into the etiology of esophageal adenocarcinoma. <i>Cancer Epidemiol Biomarkers Prev; 24(11); 1739–47. ©2015 AACR</i>.</p></div>Keywords:
Heartburn
Barrett's esophagus
Reflux esophagitis
Genome-wide Association Study
Esophageal disease
Abstract Background and Aim: Epidemiological studies have shown that 10–48% of people in developed countries have gastroesophageal reflux disease (GERD) symptoms such as heartburn and acid regurgitation. The present study aimed to examine the prevalence of GERD symptoms and GERD in Japanese subjects. Methods: A cross‐sectional study of Japanese subjects who visited a clinic for a routine health check up was carried out. Subjects were asked to fill out a self‐report questionnaire. GERD was defined as the presence of heartburn and/or acid regurgitation at least twice per week. Results: Of the 6035 eligible subjects, 2662 (44.1%) reported having had heartburn and/or acid regurgitation during the past year: 124 (2.1%) daily, 275 (4.6%) twice per week, 773 (12.8%) twice per month and 1490 (24.7%) less than twice per month. Three hundred and ninety‐nine (6.6%) subjects were diagnosed as having GERD and there was no relationship between the prevalence of GERD and either sex or age. The prevalence of bothersome GERD symptoms was significantly higher in subjects with GERD than in those without GERD. Conclusion: Approximately 6.6% of Japanese have GERD and most persons with GERD described heartburn or acid regurgitation as bothersome.
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In the past there has been reliance on heartburn and acid regurgitation as the cardinal symptoms of gastro-esophageal reflux. Now it is recognized that diverse additional symptoms including extraesophageal manifestations are essential components of gastroesophageal reflux disease (GERD). Furthermore, previous reliance in mucosal damage at endoscopy as evidence of therapeutic success in the management of GERD has proven of only limited value in the diverse world of GERD symptoms. Indeed is now apparent that the relationship between symptoms and lesions is modest at best. Most patients with GERD have no overt erosions or ulceration at endoscopy and they frequently suffer from a wide array of complaints other than heartburn that contribute to their diminished perception of life's quality. To address these problems, multidimensional questionnaires designed to encompass the diverse symptomatology of GERD have been investigated, principally, to provide a reproducible metric of change in the subjective response to pharmacologic therapy during trials for patients with nonerosive reflux disease. The most promising of these instruments is The ReQuest questionnaire, because it has been extensively validated in multiple patient groups and cultures, appears highly promising in this regard and for erosive disease too and may ultimately prove to be of value for the initial evaluation of patients with GERD. We propose that accurate symptom delineation complemented with endoscopy performed in selected groups of patients will become the mainstay in diagnosis of GERD and the assessment of therapy efficacy.
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Symptomatic gastroesophageal reflux disease (GERD) is a common problem that affects a substantial proportion of the American population. It is estimated that the symptoms of GERD may afflict 40% to 45% of Americans each month. The diagnosis of GERD can be difficult, as its symptoms vary from typical symptoms like heartburn to atypical symptoms such as hoarseness, coughing, and chest pain. Most patients present with typical symptoms and are diagnosed with GERD if they respond to empiric trials of acid suppression. Many tests are available to help with diagnosing GERD in patients who either present with atypical symptoms or who do not respond to acid suppression; however, each test has its own shortcomings. The only test that directly measures whether acid is refluxing into the esophagus is the pH probe, but this test is uncomfortable for the patient, can be difficult to interpret, and may not be necessary in all cases. This article reviews the indications for pH monitoring, its technique, its advantages and limitations, and its role the diagnosis of GERD.
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Department of Internal Medicine, SungkyunGastroesophageal reflux disease (GERD) is characterized by the presence of esophageal mucosal injury or by the occurrence of reflux-induced symptoms which are severe enough to impair quality of life. GERD is a common GI disorder in the West, but not in the East including Korea. Heartburn is the most common symptom of GERD in the West, but it is rare in a substantial proportion of patients with GERD in Korea. Epigastric soreness or pain of Korean patients could result from gastroesophageal reflux. The suppression of acid is the mainstay of therapy for GERD. Proton pump inhibitors can be an attractive choice of initial treatment because of rapid symptom relief and healing of esophagitis. Because GERD is a chronic relapsing disorder, most of patients require long-term management. For long-term management of GERD, step-down approach is recommendable considering clinical and economic effectiveness.
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OBJECTIVES: Nocturnal heartburn and related sleep disturbances are common among patients with gastroesophageal reflux disease (GERD). This study evaluated the efficacy of dexlansoprazole MR 30 mg in relieving nocturnal heartburn and GERD-related sleep disturbances, improving work productivity, and decreasing nocturnal symptom severity in patients with symptomatic GERD. METHODS: Patients (N=305) with frequent, moderate-to-very severe nocturnal heartburn and associated sleep disturbances were randomized 1:1 in a double-blind fashion to receive dexlansoprazole MR or placebo once daily for 4 weeks. The primary end point was the percentage of nights without heartburn. Secondary end points were the percentage of patients with relief of nocturnal heartburn and of GERD-related sleep disturbances over the last 7 days of treatment. At baseline and week 4/final visit, patients completed questionnaires that assessed sleep quality, work productivity, and the severity and impact of nocturnal GERD symptoms. RESULTS: Dexlansoprazole MR 30 mg (n=152) was superior to placebo (n=153) in median percentage of nights without heartburn (73.1 vs. 35.7%, respectively;P<0.001). Dexlansoprazole MR was significantly better than placebo in percentage of patients with relief of nocturnal heartburn and GERD-related sleep disturbances (47.5 vs. 19.6%, 69.7 vs. 47.9%, respectively;P<0.001), and led to significantly greater improvements in sleep quality and work productivity and decreased nocturnal symptom severity. Adverse events were similar across treatment groups. CONCLUSIONS: In patients with symptomatic GERD, dexlansoprazole MR 30 mg is significantly more efficacious than placebo in providing relief from nocturnal heartburn, in reducing GERD-related sleep disturbances and the consequent impairments in work productivity, and in improving sleep quality/quality of life.
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Gastroesophageal reflux disease (GERD) is a common upper gastrointestinal disorder characterized by troublesome symptoms, including heartburn and acid regurgitation. GERD is associated with complications such as peptic stricture, Barrett's esophagus, and esophageal adenocarcinoma, and it negatively affects quality of life (QoL).
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