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Gastric cancer in Lynch syndrome is associated with underlying immune gastritis
  1. Tomer Adar1,
  2. Madeline Friedman1,
  3. Linda H Rodgers2,
  4. Kristen M Shannon2,
  5. Lawrence R Zukerberg3,
  6. Daniel C Chung1,2
  1. 1 Gastroenterology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States
  2. 2 Center for Cancer Risk Assessment, Cancer Center, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, United States
  3. 3 Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States
  1. Correspondence to Dr Daniel C Chung, Massachusetts General Hospital, Boston, MA 02114, USA; chung.daniel{at}

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Lynch syndrome is the most common cause of hereditary colon cancer but is also associated with gastric cancer.1 Interestingly, gastric cancer was a distinguishing feature of the original Lynch pedigree described in 1913.2 Currently, the standardised incidence ratio (SIR) for gastric cancer in Lynch syndrome is estimated to be 3.4.3 Among 255 gene-positive patients with Lynch followed prospectively in our Hereditary Gastrointestinal Cancer programme, 7 (2.7%, 95% CI 1.3% to 5.7%) were diagnosed with gastric cancer at a median age of 55 years. Six carried an MSH2 mutation, five were women and five exhibited underlying chronic immune-mediated gastritis.

Patients with Lynch syndrome, defined by a germline mutation in a DNA mismatch repair gene, were first identified in a REDCap-based Hereditary GI Cancer registry of individuals followed longitudinally at an academic centre, and clinical and endoscopic features were reviewed in those with a new diagnosis of gastric cancer. SIRs were calculated using age and an age-adjusted and gender-adjusted rate from the Surveillance Epidemiology and End Result (SEER) database.4

Among the 255 individuals (102 men and 153 women) identified with Lynch syndrome, the following was the distribution of germline mutations: MSH2 (n=93, 36.5%), MSH6 (n=63, 24.7%), MLH1 (n=58, 22.8%), PMS2 (n=33, 12.9%) and EPCAM (n=8, 3.1%). Overall, there were more than 13 000 person-years of observation, with an average age …

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  • Contributors Conception and design: TA, LR, KS and DC. Collection and assembly of data: TA, MF, LR, KS, LZ and DC. Data analysis and interpretation: TA, LR, KS and DC. Manuscript writing: TA, MF, LR, KS, LZ and DC.

  • Funding This work was conducted with support from Harvard Catalyst | The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award UL1 TR001102) and financial contributions from Harvard University and its affiliated academic healthcare centres. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic healthcare centres, or the National Institutes of Health. TA is a recipient of fellowship grants from the American Physicians Fellowship for Medicine in Israel, Israel Cancer Association and Israel Gastroenterology Association.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.