2. Academic Validation
  3. The first case report of polymerase proofreading-associated polyposis in POLD1 variant, c.1433G>A p.S478N, in Japan

The first case report of polymerase proofreading-associated polyposis in POLD1 variant, c.1433G>A p.S478N, in Japan

  • Jpn J Clin Oncol. 2020 Sep 5;50(9):1080-1083. doi: 10.1093/jjco/hyaa090.
Tetsuya Ito 1,  Tadashi Nomizu 2,  Hidetaka Eguchi 3,  Nao Kamae 4,  Sariya Dechamethakun 3,  Yoshinori Akama 5,  Goichi Endo 6,  Kokichi Sugano 7,  Teruhiko Yoshida 8,  Yasushi Okazaki 3,  Hideyuki Ishida 1
Affiliations

Affiliations

  • 1 Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Kawagoe.
  • 2 Department of Surgery, Hoshi General Hospital, Koriyama.
  • 3 Diagnosis and Therapeutics of Intractable Disease, Juntendo University Graduate School of Medicine, Tokyo.
  • 4 Department of Clinical Genetics, Saitama Medical Center, Saitama Medical University, Kawagoe.
  • 5 Department of Genetic Counseling, Hoshi General Hospital, Koriyama.
  • 6 Department of Surgery, Fukushima Red Cross Hospital, Fukushima.
  • 7 Oncogene Research Unit/Cancer Prevention Unit, Tochigi Cancer Center Research Institute, Utsunomiya.
  • 8 Department of Genetic Medicine and Services, National Cancer Center Hospital, Tokyo, Japan.
PMID: 32548621 DOI: 10.1093/jjco/hyaa090
Abstract

Polymerase proofreading-associated polyposis, caused by germline variants in the exonuclease domains of POLD1 and POLE, is a dominantly inherited rare condition characterized by oligo-adenomatous polyposis and increased risk of colorectal Cancer, endometrial Cancer and brain tumours. We report the first Japanese case of polymerase proofreading-associated polyposis carrying a POLD1 variant. The proband was a Japanese woman who had undergone resections of early colorectal carcinomas repeatedly and a hysterectomy with bilateral oophorectomy for endometrial Cancer, all of which were diagnosed within 2 years after the first colectomy at 49 year old. Colonoscopic examinations demonstrated at least 14 non-cancerous polypoid lesions, some of which were histologically confirmed to be adenoma. Multigene panel Sequencing identified a missense variant in POLD1 (c.1433G>A). Although her relatives did not undergo genetic testing, her father and paternal grandfather died of brain tumours at 53 and ~30 years of age, respectively.

Keywords

POLD1; endometrial cancer; hereditary colorectal cancer; polyposis.

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