Myo9B is associated with an increased risk of Barrett's esophagus and esophageal adenocarcinoma

Abstract Background Celiac disease (CD) has an estimated prevalence of 1% worldwide, including North America. Barrett’s esophagus (BE) is a complication of chronic gastroesophageal reflux disease (GERD), which predisposes to development of dysplasia, which can transition to esophageal adenocarcinoma (EAC). GERD is commonly found in patients with CD and there is evidence that reflux symptoms improve after starting the gluten-free diet. However, the prevalence of CD in patients with BE, and its impact on progression to EAC have not been studied. Aims To assess the prevalence of CD in patients with BE and its impact on development of dysplasia and EAC. Methods We performed a retrospective review of medical records of patients attending the Digestive Diseases Clinic and the specialized Barrett’s Clinic at McMaster University Medical Centre. We collected information related to demographics, esophageal and duodenal biopsies, as well as CD serological markers. CD diagnosis was based on the presence of Marsh III lesions in duodenal biopsies and/or positive tissue transglutaminase IgA antibodies (TTG). Categorical data was presented as n/N and %, continuous data as mean ±SD. Logistic regression was performed to estimate the association between BE and CD. For dysplasia development, Kaplan Meyer Breslow survival curve was used. Results CD was found in 1.8% of patients attending the Digestive Diseases Clinic (n=4800). Two hundred and sixteen patients with BE from the Digestive Diseases Clinic and the Barret’s Clinic (age 63 ±11.2, 70.3% males; follow-up period 7.0 ±5.5 years) were included in the analysis. Patients with or without CD were similar in demographic factors, concomitant diseases or previous surgeries, use of PPI, presence of symptoms and duration of treatment. The prevalence of CD was increased 5-fold in patients with BE (OR=6.0; 95% CI 2.1–17.4; p=0.006). BE patients with CD developed dysplasia earlier than those without CD (Long Rank 0.004; mean 6.0; 95% CI 3.0–4.97[PB1]). The risk of EAC was higher in BE patients with CD compared to those without CD (2/11 vs 2/205; OR=22.5; 95% CI 2.8–178.8; p= 0.003). The mean time for development of EAC from the time of BE diagnosis [PB2] was 1.5 years in patients with CD and 6.5 years in patients without CD. Conclusions The prevalence of CD is higher in patients with BE compared with the population attending a tertiary gastroenterology clinic, and with the general population. Patients with BE and concomitant CD are at increased risk of accelerated development of dysplasia and EAC, suggesting that both conditions may have a synergic detrimental effect. Funding Agencies CIHR

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NcoI TNF-β gene polymorphism and TNF expression are associated with an increased risk of developing Barrett's esophagus and esophageal adenocarcinoma

Scandinavian Journal of Gastroenterology ◽

10.3109/00365521.2011.650192 ◽

2012 ◽

Vol 47 (4) ◽

pp. 378-386 ◽

Cited By ~ 12

Author(s):

Vivianda Menke ◽

Katinka P.M. van Zoest ◽

Leon M.G. Moons ◽

Bettina Hansen ◽

Raymond G.J. Pot ◽

...

Keyword(s):

Gene Polymorphism ◽

Barrett’S Esophagus ◽

Esophageal Adenocarcinoma ◽

Barrett's Esophagus ◽

Increased Risk

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The Y-chromosome F haplogroup contributes to the development of Barrett’s esophagus-associated esophageal adenocarcinoma in a white male population

Diseases of the Esophagus ◽

10.1093/dote/doaa011 ◽

2020 ◽

Vol 33 (9) ◽

Cited By ~ 1

Author(s):

W M Westra ◽

A M Rygiel ◽

N Mostafavi ◽

G M J de Wit ◽

A L Roes ◽

...

Keyword(s):

Barrett’S Esophagus ◽

Esophageal Adenocarcinoma ◽

Barrett's Esophagus ◽

White Male ◽

Genomic Analysis ◽

Male Population ◽

Low Frequencies ◽

Univariate Logistic Regression Analysis ◽

White Males ◽

Increased Risk

Summary Barrett’s esophagus (BE) is a metaplastic condition of the distal esophagus, resulting from longstanding gastroesophageal reflux disease (GERD). BE predisposes for the highly malignant esophageal adenocarcinoma (EAC). Both BE and EAC have the highest frequencies in white males. Only a subset of patients with GERD develop BE, while <0.5% of BE will progress to EAC. Therefore, it is most likely that the development of BE and EAC is associated with underlying genetic factors. We hypothesized that in white males, Y-chromosomal haplogroups are associated with BE and EAC. To investigate this we conducted a multicenter study studying the frequencies of the Y-chromosomal haplogroups in GERD, BE, and EAC patients. We used genomic analysis by polymerase chain reaction and restriction fragment length polymorphism to determine the frequency of six Y-chromosomal haplogroups (DE, F(xJ,xK), K(xP), J, P(xR1a), and R1a) between GERD, BE, and EAC in a cohort of 1,365 white males, including 612 GERD, 753 BE patients, while 178 of the BE patients also had BE-associated EAC. Univariate logistic regression analysis was used to compare the outcomes. In this study, we found the R1a (6% vs. 9%, P = 0.04) and K (3% vs. 6%, P = 0.035) to be significantly underrepresented in BE patients as compared to GERD patients with an odds ratio (OR) of 0.63 (95% CI 0.42–0.95, P = 0.03) and of 0.56 (95% CI 0.33–0.96, P = 0.03), respectively, while the K haplogroup was protective against EAC (OR 0.30; 95% CI 0.07–0.86, P = 0.05). A significant overrepresentation of the F haplogroup was found in EAC compared to BE and GERD patients (34% vs. 27% and 23%, respectively). The F haplogroup was found to be a risk factor for EAC with an OR of 1.5 (95% CI 1.03–2.19, P = 0.03). We identified the R1a and K haplogroups as protective factors against development of BE. These haplogroups have low frequencies in white male populations. Of importance is that we could link the presence of the predominantly occurring F haplogroup in white males to EAC. It is possible that this F haplogroup is associated to genetic variants that predispose for the EAC development. In future, the haplogroups could be applied to improve stratification of BE and GERD patients with increased risk to develop BE and/or EAC.

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