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.
- 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.
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.