Satoshi Teramae1, Naoki Muguruma1, Koichi Okamoto1, Kumiko Oseto2, Ryutaro Nishikawa2, Takayuki Tanoue3, Keiji Hirata3, Shunichi Yanai4, Takayuki Matsumoto4, Seiji Shimizu5, Jun Miwa6, Yu Sasaki7, Kazuo Yashima8, Hiroyuki Ohnuma9, Yasushi Sato9, Yoshitaka Kitayama10, Yoshio Ohda10, Atsushi Yamauchi11, Yoji Sanomura12, Kumiko Tanaka13, Yoshiaki Kubo14, Hideki Ishikawa15, Yoshimi Bando16, Tomoko Sonoda17, Tetsuji Takayama18. 1. Department of Gastroenterology and Oncology, Tokushima University Graduate School of Biomedical Sciences, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan. 2. Department of Obstetrics and Gynecology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan. 3. Department of Surgery I, School of Medicine, University of Occupational and Environmental Health, Fukuoka, Japan. 4. Division of Gastroenterology, Department of Internal Medicine, Iwate Medical University, Iwate, Japan. 5. Department of Gastroenterology, Osaka General Hospital of West Japan Railway Company, Osaka, Japan. 6. Department of Gastroenterology, Toshiba Hospital, Tokyo, Japan. 7. Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata, Japan. 8. Department of Gastroenterology, Tottori University Hospital, Tottori, Japan. 9. Department of Medical Oncology, Sapporo Medical University, Hokkaido, Japan. 10. Department of Internal Medicine, Division of Gastroenterology and Hepatology, Hyogo College of Medicine, Hyogo, Japan. 11. Department of Gastroenterology and Hepatology, Tazuke Kofukai Medical Research Institute, Kitano Hospital, Osaka, Japan. 12. Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan. 13. The Post-Graduate Education Center, Tokushima University Hospital, Tokushima University, Tokushima, Japan. 14. Department of Dermatology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan. 15. Department of Molecular-Targeting Cancer Prevention, Kyoto Prefectural University of Medicine, Kyoto, Japan. 16. Division of Pathology, Tokushima University Graduate School, Tokushima, Japan. 17. Department of Public Health, Sapporo Medical University School of Medicine, Hokkaido, Japan. 18. Department of Gastroenterology and Oncology, Tokushima University Graduate School of Biomedical Sciences, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan. takayama@tokushima-u.ac.jp.
Abstract
BACKGROUND: Cowden syndrome (CS) is an autosomal-dominant hereditary disorder caused by a germline PTEN variant and characterized by multiple hamartomas and a high risk of cancers. However, no detailed data on CS in Asian patients nor genotype-phenotype correlation have been reported. METHODS: We performed the first Japanese nationwide questionnaire survey on CS and obtained questionnaire response data on 49 CS patients. RESULTS: Patients included 26 females (median age 48 years). The incidence of breast, thyroid, endometrium, and colorectal cancer was 32.7%, 12.2%, 19.2% (among females), and 6.1%, respectively. The incidence of any cancers was relatively high among all patients (46.9%, 23/49), and particularly female patients (73.1%, 19/26), compared with previous reports from Western countries. Gastrointestinal (GI) polyps were more frequently found throughout the GI tract compared with previous studies. PTEN variants were detected in 95.6% (22/23) of patients; 12 in the N-terminal region (11 in phosphatase domain) and 10 in the C-terminal (C2 domain) region. The incidence of cancer in the C2 domain group was significantly higher than in the N-terminal region (phosphatase) group. All female patients with C2 domain variant had breast cancer. CONCLUSION: Our data suggest that Japanese patients with CS, particularly female patients and patients with C2 domain variant may have a high risk of cancers.
BACKGROUND: Cowden syndrome (CS) is an autosomal-dominant hereditary disorder caused by a germline PTEN variant and characterized by multiple hamartomas and a high risk of cancers. However, no detailed data on CS in Asian patients nor genotype-phenotype correlation have been reported. METHODS: We performed the first Japanese nationwide questionnaire survey on CS and obtained questionnaire response data on 49 CS patients. RESULTS: Patients included 26 females (median age 48 years). The incidence of breast, thyroid, endometrium, and colorectal cancer was 32.7%, 12.2%, 19.2% (among females), and 6.1%, respectively. The incidence of any cancers was relatively high among all patients (46.9%, 23/49), and particularly female patients (73.1%, 19/26), compared with previous reports from Western countries. Gastrointestinal (GI) polyps were more frequently found throughout the GI tract compared with previous studies. PTEN variants were detected in 95.6% (22/23) of patients; 12 in the N-terminal region (11 in phosphatase domain) and 10 in the C-terminal (C2 domain) region. The incidence of cancer in the C2 domain group was significantly higher than in the N-terminal region (phosphatase) group. All female patients with C2 domain variant had breast cancer. CONCLUSION: Our data suggest that Japanese patients with CS, particularly female patients and patients with C2 domain variant may have a high risk of cancers.
Authors: J I Risinger; K Hayes; G L Maxwell; M E Carney; R K Dodge; J C Barrett; A Berchuck Journal: Clin Cancer Res Date: 1998-12 Impact factor: 12.531