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INTRODUCTION: Magnetic resonance enterography (MRE) is a relatively new imaging modality that involves small bowel distension with orally administered fluid. Few studies have assessed its impact on patient management. AIM: The aim of this study was to determine whether MRE influenced the management of patients with established small bowel Crohn's disease (CD). MATERIALS AND METHODS: From a prospectively maintained database of patients with inflammatory bowel disease, we identified patients with small bowel CD who underwent MRE between January 2007 and December 2010. The results of the MRE and subsequent changes in patient management within 1 month were evaluated. RESULTS: Thirty women and 27 men with CD were included. Seven patients (12%) had a normal MRE. Forty-two of 57 (74%) patients had a change in management, and 41/50 (82%) patients with an abnormal MRE had changes in management (P<0.0008). After MRE, 20/42 (47%) patients had surgery and 22/42 (53%) had changes in medical treatment. Patients with stricturing disease had more surgical intervention (P=0.02), and patients with active disease on MRE had more medical intervention (P=0.0001). Patients with two or more abnormalities on MRE had more surgery compared with medical therapy (P=0.02). CONCLUSION: The majority of patients with small bowel CD had a change in management as a result of the MRE. Because of its high clinical impact on patient management, MRE should become one of the preferred methods of small bowel evaluation in CD. Specific MRE findings may help to stratify treatment options, however, further work is required to validate this.
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Enfermedad de Crohn/diagnóstico , Intestino Delgado/patología , Imagen por Resonancia Magnética/métodos , Adolescente , Adulto , Anciano , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/cirugía , Femenino , Humanos , Obstrucción Intestinal/diagnóstico , Obstrucción Intestinal/etiología , Obstrucción Intestinal/cirugía , Intestino Delgado/cirugía , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto JovenRESUMEN
OBJECTIVES: To investigate the association of genetic polymorphisms of the interleukin-18 (IL-18) pathway to Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). Most cases of EAC arise in a background of reflux-induced BE. Genetic influences in this pathway are poorly understood. IL-18 is a multifunctional cytokine implicated in anti-tumor immunity. A number of polymorphisms of the IL-18 and IL-18 receptor-accessory protein (IL-18RAP) genes have been reported to alter gene expression and have recently been linked to inflammatory processes and various tumors, but have not heretofore been studied in BE and EAC. METHODS: Two IL-18 promoter polymorphisms -137 G/C and -607 C/A, (rs187238 and rs1946518) and one IL-18RAP polymorphism (rs917997, C/T) were analyzed. Each single-nucleotide polymorphism (SNP) was genotyped in the following groups: EAC, BE, reflux esophagitis (RE), and controls and analyzed for association with disease status. RESULTS: The IL-18RAP rs917997C allele is strongly associated with a protective effect in BE (P = 0.0002) and EAC (P = 6 × 10(-7)), which approaches genome-wide levels of significance for allele association without incurring significant multiple testing. The CC genotype at IL-18RAP locus rs917997 was associated with a protective effect against esophageal disease (P = 6 × 10(-4), odds ratio (OR) = 0.59, and 95% confidence interval (CI) 0.43-0.80 for BE; and P = 2 × 10(-6), OR = 0.46, and 95% CI 0.34-0.64 for EAC). The genotype frequencies of IL-18-607 C/A were weakly associated with BE (P = 0.02), and this trend was also seen between controls and EAC (P = 0.07). The CC genotype was associated with an increased risk of BE (OR = 1.45, 95% CI 1.07-1.98) and approached significance for EAC (OR = 1.34, 95% CI 0.98-1.82). Allele and genotype frequencies at these loci were not significantly different between the RE group and controls. Although no significant association was observed between the disease groups at the -137 G/C locus, the -137G/-607C haplotype was associated with increased risk of BE (P = 0.006) with haplotype frequencies of 55% in controls and 65% in BE. CONCLUSIONS: These data show a strong association of the IL-18RAP SNP rs917997 locus with BE and EAC and suggestive association of the Barrett's population with the IL-18-607 C/A promoter polymorphism. As both of these SNPs have been demonstrated as expression quantitative trait loci affecting expression of the respective genes, this strongly implicates IL-18 signaling in susceptibility to BE and EAC.
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Adenocarcinoma/genética , Esófago de Barrett/genética , Neoplasias Esofágicas/genética , Interleucina-18/genética , Polimorfismo de Nucleótido Simple , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Esófago de Barrett/patología , Neoplasias Esofágicas/patología , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Regiones Promotoras Genéticas , Transducción de SeñalRESUMEN
Double balloon enteroscopy has been available since 2004 and is slowly emerging as a valuable procedure that has the potential to reach all parts of the small intestine, allowing biopsy and therapeutic intervention. This paper describes the background to its development, the mechanics of the procedure and the current and potential roles it has in relation to small bowel Crohn's disease.
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Enfermedad de Crohn/diagnóstico , Enteroscopía de Doble Balón , Enfermedad de Crohn/diagnóstico por imagen , Humanos , Tomografía Computarizada por Rayos XAsunto(s)
Dolor Abdominal/diagnóstico , Dolor Abdominal/etiología , Paniculitis Peritoneal/diagnóstico , Paniculitis Peritoneal/fisiopatología , Anciano , Biopsia , Histocitoquímica , Humanos , Laparotomía , Masculino , Microscopía , Paniculitis Peritoneal/patología , Radiografía Abdominal , Tomografía Computarizada por Rayos XRESUMEN
Visualization of the entire small-bowel mucosa had not been possible until the development of the capsule endoscope (Pillcam, Given Imaging, Yoqneam, Israel). However, this device did not allow any endoscopic intervention. More recently, a double balloon endoscope has been developed that allows intubation of the entire small bowel. This endoscope contains a working channel that allows for all the interventions possible with standard colonoscopes. In this review we describe the instrument, techniques for its use, and its practical applications and capabilities. We review the experience to date for its use in various clinical indications for small-bowel inflammatory disease, its diagnostic and therapeutic yield and risks, and its role and potential in the diagnosis and treatment of inflammatory bowel disease.
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Enfermedad de Crohn/diagnóstico , Enteroscopía de Doble Balón , HumanosRESUMEN
The role of antioxidants in the pathogenesis of reflux esophagitis (RE), Barrett's esophagus (BE), and esophageal adenocarcinoma (EAC) remains unknown. We evaluated the associations among dietary antioxidant intake and these diseases. We performed an assessment of dietary antioxidant intake in a case control study of RE (n = 219), BE (n = 220), EAC (n = 224), and matched population controls (n = 256) (the Factors Influencing the Barrett's Adenocarcinoma Relationship study) using a modification of a validated FFQ. We found that overall antioxidant index, a measure of the combined intake of vitamin C, vitamin E, total carotenoids, and selenium, was associated with a reduced risk of EAC [odds ratio (OR) = 0.57; 95% CI = 0.33-0.98], but not BE (OR = 0.95; 95% CI = 0.53-1.71) or RE (OR = 1.60; 95% CI = 0.86-2.98), for those in the highest compared with lowest category of intake. Those in the highest category of vitamin C intake had a lower risk of EAC (OR = 0.37; 95% CI = 0.21-0.66; P-trend = 0.001) and RE (OR = 0.46; 95% CI = 0.24-0.90; P-trend = 0.03) compared with those in the lowest category. Vitamin C intake was not associated with BE, and intake of vitamin E, total carotenoids, zinc, copper, or selenium was not associated with EAC, BE, or RE. In conclusion, the overall antioxidant index was associated with a reduced risk of EAC. Higher dietary intake of vitamin C was associated with a reduced risk of EAC and RE. These results suggest that antioxidants may play a role in the pathogenesis of RE and EAC and may be more important in terms of progression rather than initiation of the disease process.
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Adenocarcinoma/prevención & control , Antioxidantes/administración & dosificación , Esófago de Barrett/prevención & control , Dieta , Reflujo Gastroesofágico/prevención & control , Minerales/administración & dosificación , Anciano , Ácido Ascórbico/administración & dosificación , Carotenoides/administración & dosificación , Estudios de Casos y Controles , Cobre/administración & dosificación , Neoplasias Esofágicas/prevención & control , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Factores de Riesgo , Selenio/administración & dosificación , Vitamina E/administración & dosificación , Zinc/administración & dosificaciónRESUMEN
BACKGROUND & AIMS: Alcohol consumption may increase gastroesophageal reflux symptoms, cause damage to the esophageal mucosa, and/or promote carcinogenesis. However, reports about the association between alcohol and reflux esophagitis, Barrett's esophagus, and esophageal adenocarcinoma are conflicting. METHODS: Information relating to alcohol consumption, at age 21 and 5 years before the interview date, was collected from 230 reflux esophagitis, 224 Barrett's esophagus, and 227 esophageal adenocarcinoma patients and 260 frequency-matched population controls. Logistic regression analyses were used to compare alcohol consumption in the 3 case groups to controls with adjustment for potential confounders. RESULTS: Population controls reporting gastroesophageal reflux symptoms were less likely than controls without symptoms to drink alcohol 5 years before the interview date (odds ratio [OR], 0.44, 0.20-0.99). No associations were observed between total alcohol consumption 5 years before the interview date and reflux esophagitis, Barrett's esophagus, or esophageal adenocarcinoma (OR, 1.26, 0.78-2.05; OR, 0.72, 0.43-1.21; and OR, 0.75, 0.46-1.22, respectively). Wine was inversely associated with reflux esophagitis (OR, 0.45, 0.27-0.75). Total alcohol consumption at age 21 years was significantly associated with reflux esophagitis (OR, 2.24, 1.35-3.74) but not with Barrett's esophagus or esophageal adenocarcinoma (OR, 1.06, 0.63-1.79 and OR, 1.27, 0.77-2.10, respectively). CONCLUSIONS: Alcohol consumption in early adulthood may lead to the development of reflux esophagitis. More recent alcohol consumption does not appear to confer any increased risk of reflux esophagitis, Barrett's esophagus, or esophageal adenocarcinoma. In fact, wine consumption may reduce the risk of these 3 esophageal disorders.
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Adenocarcinoma/epidemiología , Consumo de Bebidas Alcohólicas/epidemiología , Esófago de Barrett/epidemiología , Neoplasias Esofágicas/epidemiología , Esofagitis Péptica/epidemiología , Adulto , Femenino , Humanos , Irlanda/epidemiología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Irlanda del Norte/epidemiología , Adulto JovenRESUMEN
OBJECTIVE: To examine the association between dietary glycemic index (GI), glycemic load (GL), total carbohydrate, sugars, starch, and fiber intakes and the risk of reflux esophagitis, Barrett's esophagus, and esophageal adenocarcinoma. METHODS: In an all-Ireland study, dietary information was collected from patients with esophageal adenocarcinoma (n = 224), long-segment Barrett's esophagus (n = 220), reflux esophagitis (n = 219), and population-based controls (n = 256). Multiple logistic regression analysis examined the association between dietary variables and disease risk by tertiles of intake and as continuous variables, while adjusting for potential confounders. RESULTS: Reflux esophagitis risk was positively associated with starch intake and negatively associated with sugar intake. Barrett's esophagus risk was significantly reduced in people in the highest versus the lowest tertile of fiber intake (OR 0.44 95%CI 0.25-0.80). Fiber intake was also associated with a reduced risk of esophageal adenocarcinoma, as was total carbohydrate intake (OR 0.45 95%CI 0.33-0.61 per 50 g/d increase). However, an increased esophageal adenocarcinoma risk was detected per 10 unit increase in GI intake (OR 1.42 95%CI 1.07-1.89). CONCLUSIONS: Our findings suggest that fiber intake is inversely associated with Barrett's esophagus and esophageal adenocarcinoma risk. Esophageal adenocarcinoma risk is inversely associated with total carbohydrate consumption but positively associated with high GI intakes.
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Adenocarcinoma/epidemiología , Esófago de Barrett/epidemiología , Neoplasias Esofágicas/epidemiología , Esofagitis Péptica/epidemiología , Índice Glucémico , Adenocarcinoma/patología , Anciano , Índice de Masa Corporal , Intervalos de Confianza , Bases de Datos Factuales , Carbohidratos de la Dieta/metabolismo , Fibras de la Dieta/metabolismo , Neoplasias Esofágicas/patología , Femenino , Humanos , Entrevistas como Asunto , Irlanda/epidemiología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Factores de Riesgo , Población Rural , Factores Sexuales , Encuestas y Cuestionarios , Población Urbana , Relación Cintura-CaderaRESUMEN
Familial adenomatous polyposis (FAP) is caused by germline mutations in the adenomatous polyposis coli (APC) gene with onset of florid polyposis in childhood and development of colorectal cancer by age 30. Colectomy is advised because of the high risk of developing colorectal cancer. Attenuated FAP (AFAP) is a variant of this condition with a later age of onset and milder clinical phenotype; however, colectomy is advised once polyposis develops and polyps cannot be managed endoscopically. We report a case of a patient with AFAP and previously resected colonic carcinoma that was treated with chemoprophylaxis with long-term cyclooxygenase-2 (COX-2) inhibitors after declining colectomy. Colonoscopic examination demonstrated regression of polyps by 18 months. After 9 years of follow-up, there was no evidence of colorectal cancer development or progression of polyposis. This is the first case report on long-term treatment with COX-2 inhibition in a patient with AFAP and previous colonic carcinoma.
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Poliposis Adenomatosa del Colon/tratamiento farmacológico , Neoplasias del Colon/tratamiento farmacológico , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
BACKGROUND: There are few studies that describe the medical treatment and colitis response rates among patients with a severe relapse of inflammatory bowel disease (IBD) during pregnancy, and few studies of the effect of such a relapse on birth outcomes in these patients. OBJECTIVES: To describe the treatment and response rates of severe colitis in pregnancy, and to assess the effects of a severe relapse of colitis during pregnancy on birth outcomes. METHODS: We performed a case control study of pregnant patients with IBD hospitalized for a disease relapse at two large treatment centers between 1989 and 2001. Details of management of disease relapse and maternal and fetal outcomes were recorded. RESULTS: Eighteen patients (11 ulcerative colitis, 6 Crohn's disease, 1 indeterminate colitis), mean age 28.6 yr (range 19-38) formed the study group; 41 age-matched pregnant IBD patients without disease relapse formed the control group. Study patients were hospitalized at a mean of 15.9-wk gestation (range 8-35) for a mean of 10.4 days (range 3-31). All 18 patients received IV hydrocortisone (mean dose 199 mg/day) and 7 patients (39%) either continued taking or were commenced on immunomodulators: IV cyclosporine (5 patients) and azathioprine/6-MP (3 patients). Fifteen patients (83%) had a clinical response to these medical treatments, 3 patients required colectomy. There were significant differences between study and control groups in gestation period (35.0 wk vs 38.7 wk, respectively, P= 0.0001) and birth weight (2,001 g vs 3,018 g, respectively, P < 0.0001). CONCLUSIONS: Treatment with IV hydrocortisone and IV cyclosporine appears effective at inducing remission of colitis but their use must continue to be confined to severely ill patients being treated at specialized centers. Severe relapses of colitis during pregnancy increase the risk of preterm birth and low birth weight.
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Colectomía , Colitis Ulcerosa/terapia , Enfermedad de Crohn/terapia , Hospitalización , Inmunosupresores/uso terapéutico , Complicaciones del Embarazo/terapia , Resultado del Embarazo , Adulto , Puntaje de Apgar , Azatioprina/efectos adversos , Azatioprina/uso terapéutico , Estudios de Casos y Controles , Cesárea , Colitis Ulcerosa/inmunología , Enfermedad de Crohn/inmunología , Ciclosporina/efectos adversos , Ciclosporina/uso terapéutico , Quimioterapia Combinada , Femenino , Humanos , Hidrocortisona/efectos adversos , Hidrocortisona/uso terapéutico , Inmunosupresores/efectos adversos , Recién Nacido , Infusiones Intravenosas , Embarazo , Complicaciones del Embarazo/inmunología , RecurrenciaRESUMEN
The incidence of esophageal adenocarcinoma has increased in recent years, and Barrett's esophagus is a recognized risk factor. Gastroesophageal reflux of acid and/or bile is linked to these conditions and to reflux esophagitis. Inflammatory disorders can lead to carcinogenesis through activation of "prosurvival genes," including cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Increased expression of these enzymes has been found in esophageal adenocarcinoma, Barrett's esophagus, and reflux esophagitis. Polymorphic variants in COX-2 and iNOS genes may be modifiers of risk of these conditions. In a population-based case-control study, we examined associations of the COX-2 8473 T>C and iNOS Ser(608) Leu (C>T) polymorphisms with risk of esophageal adenocarcinoma, Barrett's esophagus, and reflux esophagitis. Genomic DNA was extracted from blood samples collected from cases of esophageal adenocarcinoma (n = 210), Barrett's esophagus (n = 212), and reflux esophagitis (n = 230) and normal population controls frequency matched for age and sex (n = 248). Polymorphisms were genotyped using TaqMan allelic discrimination assays. Odds ratios and 95% confidence intervals were obtained from logistic regression models adjusted for potential confounding factors. The presence of at least one COX-2 8473 C allele was associated with a significantly increased risk of esophageal adenocarcinoma (adjusted odds ratio, 1.58; 95% confidence interval, 1.04-2.40). There was no significant association between this polymorphism and risk of Barrett's esophagus or reflux esophagitis or between the iNOS Ser 608 Leu polymorphism and risk of these esophageal conditions. Our study suggests that the COX-2 8473 C allele is a potential genetic marker for susceptibility to esophageal adenocarcinoma.
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Adenocarcinoma/enzimología , Adenocarcinoma/genética , Esófago de Barrett/enzimología , Esófago de Barrett/genética , Ciclooxigenasa 2/genética , Neoplasias Esofágicas/enzimología , Neoplasias Esofágicas/genética , Esofagitis Péptica/enzimología , Esofagitis Péptica/genética , Óxido Nítrico Sintasa de Tipo II/genética , Polimorfismo Genético , Alelos , Estudios de Casos y Controles , Femenino , Marcadores Genéticos , Variación Genética , Humanos , Modelos Logísticos , Masculino , Persona de Mediana EdadRESUMEN
Reflux of gastric contents can lead to development of reflux esophagitis and Barrett's esophagus. Barrett's esophagus is a risk factor for esophageal adenocarcinoma. Damage to DNA may lead to carcinogenesis but is repaired through activation of pathways involving polymorphic enzymes, including human 8-oxoguanine glycosylase 1 (hOGG1), X-ray repair cross-complementing 1 (XRCC1), and xeroderma pigmentosum group D (XPD). Of the single nucleotide polymorphisms identified in these genes, hOGG1 Ser 326 Cys, XRCC1 Arg 399 Gln, and XPD Lys 751 Gln are particularly common in Caucasians and have been associated with lower DNA repair capacity. Small studies have reported associations with XPD Lys 751 Gln and esophageal adenocarcinoma. XRCC1 Arg 399 Gln has been linked to Barrett's esophagus and reflux esophagitis. In a population-based case-control study, we examined associations of the hOGG1 Ser 326 Cys, XRCC1 Arg 399 Gln, and XPD Lys 751 Gln polymorphisms with risk of esophageal adenocarcinoma, Barrett's esophagus, and reflux esophagitis. Genomic DNA was extracted from blood samples collected from cases of esophageal adenocarcinoma (n = 210), Barrett's esophagus (n = 212), reflux esophagitis (n = 230), and normal population controls frequency matched for age and sex (n = 248). Polymorphisms were genotyped using TaqMan allelic discrimination assays. Odds ratios and 95% confidence intervals were obtained from logistic regression models adjusted for potential confounding factors. There were no statistically significant associations between these polymorphisms and risk of esophageal adenocarcinoma, Barrett's esophagus, or reflux esophagitis.
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Adenocarcinoma/genética , Esófago de Barrett/genética , Neoplasias Esofágicas/genética , Esofagitis Péptica/genética , Polimorfismo Genético , Estudios de Casos y Controles , Reparación del ADN , Femenino , Genotipo , Humanos , Irlanda , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
Biomarkers in inflammatory bowel disease (IBD) are needed to help in disease diagnosis, prognosis, and assessment of disease activity. The best serologic markers to date measure antibody responses to normal commensal flora. These antibody responses can provide prognostic information as well as clues to disease pathogenesis. There remains room for additional biomarkers to clarify the diagnosis for certain patients with indeterminate colitis or small bowel Crohn's disease (CD) with protean manifestations. In this issue of the Journal, Adams and colleagues describe the presence of antibodies against Bacteroides vulgatus in CD patients. This additional marker may complement existing disease markers. Future studies should address whether these antibodies can help categorize patients with indeterminate colitis or predict severity of CD.
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Enfermedad de Crohn/microbiología , HumanosRESUMEN
BACKGROUND: Intravenous cyclosporine (i.v. CsA) is an effective therapy for patients with inflammatory bowel disease (IBD). However, data regarding its adverse events in these patients are limited. METHODS: A retrospective chart review of the initial 111 consecutive patients with IBD treated with i.v. CsA followed by a predetermined duration of oral therapy. RESULTS: One hundred eleven patients (64 UC, 47 CD; mean age 33 yr, range 16-68) received i.v. CsA at 4 mg/kg/day, then oral CsA at 8 mg/kg/day, with dose adjustment based on serum creatinine. The mean treatment duration was 9.3 months (range 1 wk to 34 months). Major adverse events occurred in 17 (15.3%) patients. Nephrotoxicity (serum creatinine > or = 1.4 mg/dL [123 micromol/L] or a rise by at least 33% over baseline not responding to dose adjustment) sufficiently severe to warrant discontinuation of therapy occurred in 6 (5.4%) patients. Serious infection occurred in 7 (6.3%) patients, seizures in 4 (3.6%) patients, anaphylaxis in 1 (0.9%) patient, and death in 2 (1.8%) patients. Minor adverse events (transient effects with complete resolution either spontaneously or with dose adjustment) comprised: paresthesias (51%), hypomagnesemia (42%), hypertension (39%), hypertrichosis (27%), headache (23%), minor nephrotoxicity (defined as above but with restoration of normal serum creatinine with dose adjustment; 19% of patients), abnormal liver function tests (19%), minor infections (15%), hyperkalemia (13%), and gingival swelling (4%). CONCLUSIONS: In our initial experience, limited duration CsA therapy was frequently associated with adverse events although the majority of these were minor and responded to dose adjustment. Although not all severe adverse events can be clearly attributed to CsA use alone, its high incidence suggests that vigorous monitoring by experienced clinicians at tertiary care centers may be required.
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Ciclosporina/efectos adversos , Inmunosupresores/efectos adversos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Administración Oral , Adolescente , Adulto , Anciano , Ciclosporina/administración & dosificación , Femenino , Humanos , Inmunosupresores/administración & dosificación , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
AIM: To investigate risk factors associated with Barrett's oesophagus and oesophageal adenocarcinoma. METHODS: This all-Ireland population-based case-control study recruited 224 Barrett's oesophagus patients, 227 oesophageal adenocarcinoma patients and 260 controls. All participants underwent a structured interview with information obtained about potential lifestyle and environmental risk factors. RESULTS: Gastro-oesophageal reflux was associated with Barrett's [OR 12.0 (95% CI 7.64-18.7)] and oesophageal adenocarcinoma [OR 3.48 (95% CI 2.25-5.41)]. Oesophageal adenocarcinoma patients were more likely than controls to be ex- or current smokers [OR 1.72 (95% CI 1.06-2.81) and OR 4.84 (95% CI 2.72-8.61) respectively] and to have a high body mass index [OR 2.69 (95% CI 1.62-4.46)]. No significant associations were observed between these risk factors and Barrett's oesophagus. Fruit but not vegetables were negatively associated with oesophageal adenocarcinoma [OR 0.50 (95% CI 0.30-0.86)]. CONCLUSION: A high body mass index, a diet low in fruit and cigarette smoking may be involved in the progression from Barrett's oesophagus to oesophageal adenocarcinoma.
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Adenocarcinoma/epidemiología , Esófago de Barrett/epidemiología , Neoplasias Esofágicas/epidemiología , Anciano , Índice de Masa Corporal , Estudios de Casos y Controles , Dieta , Progresión de la Enfermedad , Femenino , Frutas , Reflujo Gastroesofágico/complicaciones , Reflujo Gastroesofágico/etiología , Humanos , Masculino , Persona de Mediana Edad , Irlanda del Norte , Factores de Riesgo , Fumar/efectos adversosAsunto(s)
Poliposis Adenomatosa del Colon/genética , ADN de Neoplasias/genética , Genes APC , Mutación , Sitios de Empalme de ARN/genética , Poliposis Adenomatosa del Colon/patología , Colonoscopía , Exones , Femenino , Estudios de Seguimiento , Predisposición Genética a la Enfermedad , Humanos , Persona de Mediana Edad , Linaje , Fenotipo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Oxidative stress appears to be important in the pathogenesis of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). Single-nucleotide polymorphisms (SNPs) of antioxidant enzyme genes may play a part in determining individual susceptibility to these diseases. The Factors Influencing the Barrett's Adenocarcinoma Relationship (FINBAR) study is a population-based, case-control study of BE and EAC in Ireland. DNA from EAC (n = 207), BE (> or =3 cm BE at endoscopy with specialized intestinal metaplasia on biopsy, n = 189) and normal population controls (n = 223) were analyzed. Several SNPs spanning the genes for glutathione S-transferase P1 (GSTP1), manganese superoxide dismutase (MnSOD) and glutathione peroxidase 2 (GPX2) were genotyped using multiplex polymerase chain reaction and SNaPshottrade mark. The chi(2) test was used to compare genotype and allele frequencies between case and control subjects. Linkage disequilibrium between SNPs was quantified using Lewontin's D' value and haplotype frequency estimates obtained using Haploview. Eleven SNPs were genotyped (six for GSTP1, three for MnSOD and two for GPX2); all were in Hardy-Weinberg equilibrium. None was significantly associated with EAC or BE even before Bonferroni correction. Odds ratios for EAC for individual SNPs ranged from 0.68 [95% confidence interval (CI) 0.43-1.08] to 1.25 (95% CI 0.73-2.16), and for BE from 0.84 (95% CI 0.52-1.30) to 1.30 (95% CI 0.85-1.97). SNPs in all three genes were in strong linkage disequilibrium (D' > 0.887) but haplotype analysis did not show any significant association with EAC or BE. SNPs involving the GSTP1, MnSOD and GPX2 genes were not associated with BE or EAC. Further studies aimed at identifying susceptibility genes should focus on different antioxidant genes or different pathways.
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Adenocarcinoma/genética , Esófago de Barrett/genética , Neoplasias Esofágicas/genética , Glutatión Peroxidasa/genética , Gutatión-S-Transferasa pi/genética , Polimorfismo de Nucleótido Simple , Superóxido Dismutasa/genética , Adenocarcinoma/enzimología , Adulto , Anciano , Anciano de 80 o más Años , Esófago de Barrett/enzimología , Estudios de Casos y Controles , Neoplasias Esofágicas/enzimología , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Observational studies suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the risk of esophageal adenocarcinoma, but it is not known at what stage they may act in the esophageal inflammation-metaplasia-adenocarcinoma sequence. In an all-Ireland case-control study, we investigated the relationship between the use of NSAIDs and risk of reflux esophagitis, Barrett's esophagus, and esophageal adenocarcinoma. Patients with esophageal adenocarcinoma, long-segment Barrett's esophagus and population controls were recruited from throughout Ireland. Esophagitis patients were recruited from Northern Ireland only. Data were collected on known and potential risk factors for esophageal adenocarcinoma and on the use of NSAIDs, including aspirin, at least 1 year before interview. Associations between use of NSAIDs and the stages of the esophageal inflammation-metaplasia-adenocarcinoma sequence were estimated by multiple logistic regression. In total, 230 reflux esophagitis, 224 Barrett's esophagus, and 227 esophageal adenocarcinoma and 260 population controls were recruited. Use of aspirin and NSAIDs was associated with a reduced risk of Barrett's esophagus [odds ratio [OR; 95% confidence interval (95% CI)], 0.53 (0.31-0.90) and 0.40 (0.19-0.81), respectively] and esophageal adenocarcinoma [OR (95% CI), 0.57 (0.36-0.93) and 0.58 (0.31-1.08), respectively]. Barrett's esophagus and esophageal adenocarcinoma patients were less likely than controls to have used NSAIDs. Selection or recall bias may explain these results and the results of previous observational studies indicating a protective effect of NSAIDs against esophageal adenocarcinoma. If NSAIDs have a true protective effect on the esophageal inflammation-metaplasia-adenocarcinoma sequence, they may act early in the sequence.