Tumor development in Japanese patients with Lynch syndrome

PLoS One. 2018 Apr 19;13(4):e0195572. doi: 10.1371/journal.pone.0195572. eCollection 2018.

Abstract

Background: Lynch syndrome (LS) patients have a high risk of developing various tumors. This study aimed to clarify the characteristics of tumors developing in LS patients.

Methods: This is a retrospective review of 55 LS patients treated at Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital.

Results: The median age at the diagnosis of the first malignant tumor and first LS-related tumor was 44 (range, 19-65) and 44 (range, 24-66) years, respectively. Of the 55 LS patients with developing malignant tumors, 45 (93.8%) developed an LS-related tumor as the first malignant tumor. Colorectal cancer (CRC) developed in 47 patients (85.4%), followed by endometrial cancer (n = 13, 56.5%) in females and gastric cancer (n = 10, 18.1%). In 6 gastric cancer patients, Helicobacter pylori was detected in resected specimens. Twenty-nine patients (52.7%) developed CRC and extra-colonic tumors; of these, 15 patients (48.3%) had mutations in MLH1, 10 (58.8%) in MSH2, and 4 (57.1%) in MSH6. At the age of 50, the cumulative incidence was 50.9% [95% confidence interval (CI), 36.9-63.3%] for CRC, 17.4% (95% CI, 5.2-35.6%) for endometrial cancer, and 5.5% (95% CI, 1.4-13.8%) for gastric cancer. Eight gastric cancer, one breast cancer patient, five bladder cancer patients, and one prostate cancer patient demonstrated loss of expression of the mismatch repair (MMR) protein; patients with thyroid cancer, spindle cell sarcoma, and giant cell tumors did not demonstrate this.

Conclusion: Gastric cancer incidence was high in Japanese patients with LS and associated with H. pylori infection. MMR protein deficiency caused the development of malignant tumors in LS patients.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • Colorectal Neoplasms, Hereditary Nonpolyposis / epidemiology
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics
  • Colorectal Neoplasms, Hereditary Nonpolyposis / pathology
  • Colorectal Neoplasms, Hereditary Nonpolyposis / physiopathology*
  • Female
  • Helicobacter Infections / epidemiology
  • Helicobacter Infections / genetics
  • Helicobacter Infections / pathology
  • Helicobacter Infections / physiopathology
  • Helicobacter pylori
  • Humans
  • Immunohistochemistry
  • Incidence
  • Japan
  • Male
  • Middle Aged
  • Neoplasms / epidemiology
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Neoplasms / physiopathology*
  • Retrospective Studies
  • Young Adult

Grants and funding

The present study was supported in part by the Office of Metropolitan Hospital Management, Tokyo Metropolitan Government; and the Program for Integrated Database of Clinical and Genomic Information from the Japan Agency for Medical Research and Development, AMED to TY.