Refining Risk Factors for Gastric Cancer in Patients With Lynch Syndrome to Optimize Surveillance Esophagogastroduodenoscopy

Mankaney, Gautam; Macaron, Carole; Burke, Carol A.

doi:10.1016/j.cgh.2019.10.003

Cited by 12 publications

(8 citation statements)

References 19 publications

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“…Although the current diagnosis and treatment of GC has made a breakthrough, GC is still the third leading cause of cancer death; the patient's 5-year survival rate is also very low 38 . Since reducing mortality is closely related to early diagnosis of gastric cancer, there is an urgent need to identify new tumor biomarkers for early diagnosis so that patients can be treated within the optimal treatment time and improve survival.…”

Section: Discussionmentioning

confidence: 99%

Downregulated Expression of linc-ROR in Gastric Cancer and Its Potential Diagnostic and Prognosis Value

Ding

Shi

et al. 2020

Disease Markers

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Background. Gastric cancer (GC) is one of the global mortality diseases and has a poor prognosis due to the lack of ideal tumor biomarkers. Numerous studies have shown that long noncoding RNAs (lncRNAs) can affect the occurrence and development of cancer through a variety of signaling pathways. The abnormal expression and specificity of lncRNAs in tumors make them potential biomarkers of cancers. Nevertheless, the diagnostic roles of lncRNAs in GC have been poorly understood. So this study focuses on the clinical diagnostic value of lncRNAs in GC. Materials and Methods. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to investigate the expression of the linc-ROR (long intergenic noncoding RNA, regulator of reprogramming) in 105 paired GC tissues and adjacent normal tissues. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were established to assess the diagnostic value of linc-ROR. The relationship between expression of linc-ROR and clinicopathological factors of patients with GC was further explored. Kaplan-Meier analysis was performed to evaluate the prognostic value of linc-ROR expression. Results. The linc-ROR expression level was significantly decreased in GC tissues compared with its adjacent nontumor tissues ( n = 105 , P < 0.001 ). We also discovered that linc-ROR was evidently downregulated in 68.6% (72/105) of GC tissues. The AUC’s value of linc-ROR was up to 0.6495, with sensitivity and specificity of 0.7524 and 0.5143, respectively. Intriguingly, the linc-ROR expression levels were obviously associated with tumor differentiation ( P = 0.004 ). Notably, the overall survival rate of GC patients with high expression of linc-ROR was significantly higher than those with low expression. Conclusion. Our data revealed that linc-ROR has clinical potential as a biomarker for the diagnosis of GC and assessment of its prognosis.

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Section: Discussionmentioning

confidence: 99%

Downregulated Expression of linc-ROR in Gastric Cancer and Its Potential Diagnostic and Prognosis Value

Ding

Shi

et al. 2020

Disease Markers

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“…This autosomal dominant syndrome results from germline disease-causing variants in DNA mismatch repair genes including MLH1, MSH2, MSH6, PMS2, or EPCAM. Individuals with Lynch syndrome have increased lifetime risk of multiple cancers, with the highest gastrointestinal (GI) cancer risk being for colorectal cancer (2,3). Lynch syndrome-related colorectal cancers develop at an accelerated rate with polyp to colorectal cancer progression within a few years, as opposed to 10 or more years in individuals without Lynch syndrome (4).…”

Section: Introductionmentioning

confidence: 99%

“…Currently, there is a lack of consensus among guidelines from different groups about the age at which to begin surveillance, the frequency of surveillance, and even the individuals with Lynch syndrome for which upper GI surveillance is recommended (5)(6)(7)(8)(9)(10)(11). This leads to widely variable practice patterns and can result in confusion for both patients and providers (3,6,13). Finally, as more individuals are now pursuing genetic testing due to improved access and decreasing costs, it is inevitable that Lynch syndrome will be increasingly identified, further emphasizing the need to define the most effective surveillance strategies (14).…”

Section: Introductionmentioning

confidence: 99%

Upper Endoscopic Surveillance in Lynch Syndrome Detects Gastric and Duodenal Adenocarcinomas

Kumar

Dudzik

Reed

et al. 2020

Cancer Prevention Research

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Lynch syndrome is a prevalent hereditary cancer predisposition syndrome. While colorectal cancer is the most common gastrointestinal (GI) cancer in Lynch syndrome, there is also increased risk of gastric and small intestinal cancers. Recommendations for upper GI cancer surveillance in Lynch syndrome vary widely with limited data supporting effectiveness. Herein, we collected data on individuals with a diagnosis of Lynch syndrome seen at our tertiary care referral center. We identified individuals who underwent upper endoscopy and those with upper GI cancers, and associated demographics, genetic testing results, and endoscopic information. Standard statistical analyses were performed. Among 295 individuals with Lynch syndrome seen at our center, 217 (73.6%) underwent 660 total upper endoscopies. Of these 217, precancerous upper endoscopy findings included Barrett's esophagus (7, 3.2%), gastric intestinal metaplasia (18, 8.3%), and duodenal adenomas (4, 1.8%), and Helicobacter pylori was identified in 6 (2.8%). Upper GI cancers were diagnosed in 11 individuals (3.7%), including esophageal in 1, gastric in 6, and duodenal in 4. Five (1.7%) of these upper GI cancers were identified on surveillance. Individuals with upper GI cancers identified on surveillance were older at first surveillance endoscopy, with median age 63.3 versus 44.9 years (P < 0.001). Of the upper GI cancers detected on surveillance, 80% (4/5) occurred within 2 years of last upper endoscopy and 80% were stage I. In conclusion, upper endoscopy surveillance in Lynch syndrome identifies upper GI cancers. For individuals with Lynch syndrome who undergo upper GI surveillance, a short surveillance interval may be warranted.

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“…Individuals with Lynch syndrome are at increased risk of gastric cancer [ 1 , 43 ]. Gastric cancer risk varies by pathogenic variant with MLH1 and MSH2 carriers having a higher risk compared to MSH6 and PMS2 carriers [ 44 ].…”

Section: Gastric Cancermentioning

confidence: 99%

Upper Gastrointestinal Cancer Surveillance in Lynch Syndrome

Kumar

Farha

Burke

et al. 2022

Cancers

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Lynch syndrome is a common hereditary cancer predisposition syndrome associated with increased digestive cancer risk including colorectal, gastric, and duodenal cancers. While colorectal cancer surveillance is widely accepted to be an important part of a comprehensive Lynch syndrome risk management plan, the use of upper gastrointestinal cancer surveillance in Lynch syndrome remains more controversial. Currently, upper gastrointestinal cancer surveillance guidelines for Lynch syndrome vary widely, and there is no consensus on who should undergo upper gastrointestinal cancer surveillance, how surveillance should be performed, the age at which to initiate surveillance, or how often individuals with Lynch syndrome should undergo upper gastrointestinal cancer surveillance. Fortunately, research groups around the world have been focusing on upper gastrointestinal cancer surveillance in Lynch syndrome, and recent evidence in this field has demonstrated that upper gastrointestinal cancer surveillance can be performed with identification of precancerous lesions as well as early-stage upper gastrointestinal cancers. In this manuscript, we review the upper gastrointestinal cancer risks in Lynch syndrome, differing guideline recommendations for surveillance, outcomes of upper gastrointestinal cancer surveillance, and controversies in the field, and we provide a framework based on our collective experience with which to incorporate upper gastrointestinal cancer surveillance into a risk management program for individuals with Lynch syndrome.

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Refining Risk Factors for Gastric Cancer in Patients With Lynch Syndrome to Optimize Surveillance Esophagogastroduodenoscopy

Cited by 12 publications

References 19 publications

Downregulated Expression of linc-ROR in Gastric Cancer and Its Potential Diagnostic and Prognosis Value

Downregulated Expression of linc-ROR in Gastric Cancer and Its Potential Diagnostic and Prognosis Value

Upper Endoscopic Surveillance in Lynch Syndrome Detects Gastric and Duodenal Adenocarcinomas

Upper Gastrointestinal Cancer Surveillance in Lynch Syndrome

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