P1338 - Prevalence and Risk Factors of Barrett’s Esophagus in Patients With Lynch Syndrome

Monday, October 25, 2021

10:30 AM – 4:15 PM PT

Location: Shoreline Exhibit Hall

Has Audio

Presenting Author(s)

Natalie Farha, MD

Cleveland Clinic Foundation
Cleveland, OH, United States

Natalie Farha, MD¹, David Liska, MD¹, Amit Bhatt, MD², Carole Macaron, MD¹, Carol A. Burke, MD¹
¹Cleveland Clinic Foundation, Cleveland, OH; ²Digestive Disease Institute, Cleveland Clinic Foundation, Cleveland, OH

Introduction: Lynch syndrome (LS) predisposes to upper gastrointestinal (UGI) cancer. A female patient with a germline MSH2 DNA mismatch repair (MMR) pathogenic variant (PV) and Barrett’s esophagus (BE) followed in our LS-related upper gastrointestinal endoscopy (EGD) surveillance program developed a BE-related esophageal adenocarcinoma (EAC) with loss of expression of MSH2 on immunohistochemical staining. Since BE predisposes to EAC and LS predisposes to UGI cancer, we assessed the prevalence of BE, BE-related dysplasia, and BE-related EAC and the factors associated with BE in a cohort of patients with LS.

Methods: An IRB approved, hereditary database of patients undergoing asymptomatic LS-related EGD surveillance was reviewed. BE was diagnosed by the presence of intestinal metaplasia in salmon colored mucosa >1cm above the gastroesophageal junction. Demographic, clinical, and endoscopic factors between LS patients with and without BE were compared. Unadjusted univariate logistic regression analysis was used to assess various factors’ association with BE.

Results: 323 patients with > 1 EGDs were included. 21 patients (6.5%) were diagnosed with BE. BE-associated dysplasia was observed in 2 patients (9.5%), one (4.8%) of whom developed BE-related EAC. Factors associated with BE included male gender, older age at LS diagnosis and at first and last EGD, and the presence of a hiatal hernia, especially hernia size > 3 cm. (Table 1). No association between MMR PV and presence of BE was observed.

Discussion: BE in our LS cohort occurred twice as high as the only other LS related EGD surveillance program reporting BE (Table1). Neither ours nor Kumar’s study reported the frequency of gastroesophageal reflux (GERD) in patients under LS related EGD surveillance. Importantly, the BE prevalence and frequency of BE-related dysplasia in our cohort is similar to a recent meta-analysis of adults in North America with GERD symptoms (Table 1). We confirmed many known risk factors for BE and found no obvious association with a specific MMR PV. Although we had only one case of BE-related EAC, this is 3 times more common than reported in the Eusebi study. This may represent a synergistic risk between BE-related dysplasia and LS mutagenesis. Larger studies are necessary to determine if the risk of BE, and BE-associated neoplasia, is higher in patients with LS, including those with and without symptoms of GERD.

	LS with BE N= 21 (6.5%) N, (%)	LS without BE N = 302 (93.5%) N, (%)	P-value	Odds Ratio (95% confidence interval)
Male	13 (61.9)	106 (35.1)	0.03	3.00 (1.21-7.48)
MMR PV *MSH2* *MLH1* *MSH6* *PMS2*	8 (38.1) 4 (19) 6 (28.6) 3 (14.3)	109 (36.1) 85 (28.1) 67 (22.2) 41 (13.6)	>0.99 0.52 0.59 >0.99	1.09 (0.44-2.71) 0.60 (0.20-1.84) 1.40 (0.52-3.76) 1.06 (0.30-3.76)
Age at LS diagnosis (years, [quartiles])	54.3 [45.3, 59.5]	47.9 [35.3, 56.2]	0.04	1.04 (1.0-1.07)
Age at 1st LS related EGD (years, [quartiles])	55.3 [49.2, 59.5]	49.1 [38.0, 58.1]	0.05	1.03 (1.0-1.07)
Age at last LS EGD (years, [quartiles])	59.5 [55.9, 63.8]	50.7 [40.3, 60.3]	0.009	1.04 (1.01-1.08)
Age at BE diagnosis (years, [quartiles])	56.0 [47.0, 59.0]	NA	NA	NA
Hiatal hernia present	19 (90.5)	97 (32.1)	< 0.001	20.1 (4.59-87.88)
Hiatal hernia size (< 3 cm vs > 3 cm)			0.003	11.19 (2.41-52.1)
Hiatal hernia < 3cm	14 (73.6)	94 (96.9)
Hiatal hernia > 3cm	5 (26.3)	3 (3.1)
*H. pylori* positive	0 (0)	10 (3.3)	>0.99	NA
Personal Hx of Ca	18 (85.7)	198 (65.6)	0.10	3.15 (0.91-10.95)
Family Hx gastric or esophageal Ca	2 (9.5)	10 (3.3)	0.18	3.07 (0.63-15.03)
History of smoking	9 (42.9)	108 (35.8)	0.68	1.35 (0.55-3.30)
History of BMI >30kg/m²	11 (52.4)	122 (40.4)	0.40	1.62 (0.67-3.94)
NSAID/Aspirin use	9 (42.9)	133 (44)	>0.99	0.95 (0.39-2.33)
PPI use	14/21 (66.7)	112/302 (37.1)	0.014	3.39 (1.33-8.66)
Prevalence of BE in Published Studies
Author/Year/Country/Design	No. Patients	Cohort	Prevalence	BE dysplasia/EAC
Current Study/2021/United States/Cohort	323	LS related EGD surveillance	6.5%	9.5%/4.8%
Kumar/2020/United States/Cohort¹	295	LS related EGD surveillance	3.2%	ND
Eusebi/2021/North America/Meta-analysis²	26521	Patients with GERD	7.2%	13.9%/1.2%

Table: Title: Table 1: Demographic, clinical, and endoscopic features of Barrett’s esophagus in Lynch syndrome
Abbreviations: BE: Barrett’s esophagus, MMR = mismatch repair, PV = pathogenic variant, LS = lynch syndrome, EGD = esophagogastroduodenoscopy, H. pylori = helicobacter pylori, BMI = body mass index, NSAID = nonsteroidal anti-inflammatory drug, PPI = proton pump inhibitor, GERD = gastroesophageal reflux disease, NA = not applicable, ND = not described; Hx = history, Ca= cancer

Disclosures:

Natalie Farha indicated no relevant financial relationships.

David Liska indicated no relevant financial relationships.

Amit Bhatt indicated no relevant financial relationships.

Carole Macaron indicated no relevant financial relationships.

Carol Burke indicated no relevant financial relationships.

Natalie Farha, MD¹, David Liska, MD¹, Amit Bhatt, MD², Carole Macaron, MD¹, Carol A. Burke, MD¹. P1338 - Prevalence and Risk Factors of Barrett’s Esophagus in Patients With Lynch Syndrome, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.