Risk of Gastric Cancer and Utility of Endoscopic Screening for Lynch Syndrome Patients

Abstract

Background: Lynch syndrome (LS) is an autosomal dominant hereditary condition associated with a genetic predisposition to several cancers. Prior studies have shown an increased risk of gastric cancer (GC) in LS patients. The aim of this study was to synthesize the evidence for gastric cancer risk across Lynch syndrome-associated mutations and to assess the diagnostic utility of endoscopic screening for gastric cancer in these patients. Methods: A systematic literature review and meta-analysis of LS-associated gastric cancer risk and the diagnostic utility of endoscopic gastric cancer screening was conducted in accordance with PRISMA guidelines and GRADE methodology. Results: The results of this study found an elevated risk of GC in LS patients. Cumulative lifetime risk of GC in LS patients ranged from 2.6% to 38.7% when assessing across all LS mutations. Cumulative incidence ranged from 2.0% to 41.0%. When assessing cumulative incidence across specific LS mutations, MSH2 mutation carriers showed the highest cumulative incidence. RR across specific mutation carriers was generally highest in MSH2 carriers. A meta-analysis of 5 studies reporting diagnostic utility of endoscopic screening for gastric cancer in LS patients revealed a 2% incidence of GC (95% CI, 1.4%−2.9%). Conclusions: Gastric cancer risk in LS patients is greater than in the general population. Endoscopic screening yields low rates of GC in LS patients. Higher quality studies including RCTs are required to more accurately define GC risk and the yield of endoscopic surveillance in LS patients.

Early-Onset Gastrointestinal Malignancies: An Investigation into a Rising Concern

“…Genetic mutations such as the CDH1 germline mutation or hMLH1 germline mutations make up 2-3% of early-onset gastric cancer cases in North America [64]. A study evaluating the risk of developing gastric cancer in patients with Lynch syndrome found that the cumulative lifetime risk ranges from 3% to 39% across all mutations (MLH1, MSH2, MSH6, PMS2, and EPCAM) [65,110]. Peutz-Jeghers syndrome (PJS) is another hereditary risk factor for early-onset gastric cancer [66].…”

“…A comprehensive review of the literature was performed. [2] Predominantly adenocarcinoma -Cardia -Non-cardia [3,4] Hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) Predominantly pancreatic ductal adenocarcinoma [5] obesity [40,41] SCC: Oral hygiene, tobacco smoking [42] H. pylori infection, obesity, heavy alcohol use [43][44][45][46][47][48][49][50] HCC: Chronic hepatitis B infection, tobacco smoking [51,52] ICC: Primary sclerosing cholangitis, parasitic infections, hepatolithiasis [53][54][55] Heavy alcohol use, tobacco smoking, diabetes, obesity [56,57] Lower dietary fiber intake, heavy alcohol use, greater red meat consumption, lack of regular nonsteroidal anti-inflammatory drug use, and lower educational level [58,59] Risks for early-onset cancer: genetic, familial Familial Barrett's esophagus [60] Family history, CDH1 germline mutation, Lynch syndrome, juvenile polyposis syndrome, Peutz-Jeghers syndrome [61][62][63][64][65][66][67] HCC: Family history of HCC, family history of hepatitis B infection [68,69] ICC: Congenital disorders of biliary tract [70] Family history of pancreatic ductal adenocarcinoma, multiple germline mutations (BRCA1/2, PALB2, APC ATM, CDKN2A, MLH1, MSH2, MSH6, PMS2, EPCAM STK11, PRSS1) [71][72][73] Lynch syndrome, familial adenomatous polyposis, juvenile polyposis syndrome, Peutz-Je...…”

Can We Impact the Incidence and Outcomes of Barrett’s Esophagus and Esophageal Adenocarcinoma?

“…8,9 This issue also contains fantastic complementary articles on screening for foregut cancers in Lynch syndrome and surveillance after surgery. 10,11 We are pleased to publish 4 original research articles this month and 1 original review as our journal continues to grow. Dr. Poggi et al share their experience with pre procedure diagnostic testing in a large cohort of bariatric surgery patient.…”

“…8,9 This issue also contains fantastic complementary articles on screening for foregut cancers in Lynch syndrome and surveillance after surgery. 10,11…”