Incidence of germline variants in Lynch syndrome-related genes among Japanese endometrial cancer patients aged 40 years or younger

Takeshi Makabe, Wataru Yamagami, Akira Hirasawa, Izumi Miyabe, Tomokazu Wakatsuki, Mari Kikuchi, Akemi Takahashi, Junko Noda, Go Yamamoto, Daisuke Aoki, Kiwamu Akagi

Research output: Contribution to journalArticlepeer-review

Abstract

[Objective] Lynch syndrome (LS) is an autosomal dominant inherited disorder caused by a germline pathogenic variant in DNA mismatch repair (MMR) genes. Endometrial cancer frequently precedes another LS-associated tumor. This study aimed to clarify the incidence and features of LS in young Japanese endometrial cancer patients. [Methods] Sixty-five patients aged 40 years or younger, who were diagnosed with endometrial cancer, were enrolled in this study. Targeted sequencing of a hereditary colorectal cancer-related gene panel including the MMR genes MLH1, MSH2, MSH6, and PMS2 was conducted on DNA samples extracted from blood cells. [Results] Overall, 6 missense variants (2 in MSH2, 2 in MSH6, and 2 in PMS2), 1 inframe deletion variant in MSH2, 1 splice variant in MSH2, and 1 two-base substitution in the 3’ untranslated region in MLH1 were detected in 9 (13.8%) patients. Among these, the splice variant c.1276G > T (p.Ile411_Gly426del16) in MSH2 was annotated as pathogenic, while other variants were of uncertain significance. The patient with the pathogenic variant had a family history of endometrial and colorectal cancer and was diagnosed with endometrial cancer at age 35. [Conclusion] The incidence of LS among Japanese endometrial cancer patients of reproductive age (≤ 40 years) in this study was at least 1.5%; however, 12.3% of patients had variants of uncertain significance in MMR genes.

Original languageEnglish
JournalInternational Journal of Clinical Oncology
DOIs
Publication statusAccepted/In press - 2021

Keywords

  • Endometrial cancer
  • Japanese
  • Lynch syndrome
  • Young

ASJC Scopus subject areas

  • Surgery
  • Hematology
  • Oncology

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