title: Causes of Cancer Death Among First-Degree Relatives in Japanese Families with Lynch Syndrome.
abstract: OBJECTIVE
  To elucidate the causes of cancer death in Japanese families with Lynch syndrome (LS).
  
  
  METHODS
  The distributions of cancer deaths in 485 individuals from 67 families with LS (35, 30, and two families with MutL homologue 1 (MLH1), MSH2, and MSH6 gene mutations, respectively), obtained from the Registry of the Japanese Society for Cancer of the Colon and Rectum were analyzed.
  
  
  RESULTS
  Among 98 cancer deaths of first-degree relatives of unknown mutation status, 53%, 19%, 13% (among females), 7% (among females) and 5% were due to colorectal, gastric, uterine, ovarian, and hepatobiliary cancer, respectively. The proportion of deaths from extra-colonic cancer was significantly higher in families with MSH2 mutation than in those with MLH1 mutation (p=0.003).
  
  
  CONCLUSIONS
  In addition to colonic and uterine cancer, management and surveillance targeting gastric, ovarian and hepatobiliary cancer are considered important for Japanese families with LS. Extra-colonic cancer in families with MSH2 mutation might require for more intensive surveillance.
authors.affiliation: Department of Surgery, Iwakuni Clinical Center, Iwakuni, Japan.
authors.forename: Kohji
authors.initials: K
authors.lastname: Tanakaya
authors.affiliation: Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Yamaguchi
authors.affiliation: Department of Molecular-Targeting Cancer Prevention, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Ishikawa
authors.affiliation: Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Hinoi
authors.affiliation: Division of Clinical Genome Research, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Furukawa
authors.affiliation: Department of Surgery 1, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Hirata
authors.affiliation: Department of Surgery, Toho University Ohashi Medical Center, Tokyo, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Saida
authors.affiliation: Clinical Research Institute, National Kyushu Cancer Center, Fukuoka, Japan.
authors.forename: Mototsugu
authors.initials: M
authors.lastname: Shimokawa
authors.affiliation: Clinical Genetic Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Arai
authors.affiliation: Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Nagahide
authors.initials: N
authors.lastname: Matsubara
authors.affiliation: Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Tomita
authors.affiliation: Major in Science, Graduate School of Science and Engineering Research, Kinki University, Higashiosaka, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tamura
authors.affiliation: Oncogene Research Unit/Cancer Prevention Unit, Tochigi Cancer Center, Utsunomiya, Japan.
authors.forename: Kokichi
authors.initials: K
authors.lastname: Sugano
authors.affiliation: Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
authors.forename: Chikashi
authors.initials: C
authors.lastname: Ishioka
authors.affiliation: Genetics Division, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Kawagoe, Japan 05hishi@saitama-med.ac.jp.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Ishida
authors.affiliation: Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sugihara
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D001661:Biliary Tract Neoplasms / Q000235:genetics / Q000401:mortality; D002423:Cause of Death; D003110:Colonic Neoplasms / Q000235:genetics / Q000401:mortality; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics* / Q000401:mortality*; D004268:DNA-Binding Proteins / Q000235:genetics; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics / Q000401:mortality; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000235:genetics / Q000401:mortality; D014594:Uterine Neoplasms / Q000235:genetics / Q000401:mortality
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein
keywords: Japan; Lynch syndrome; causes of cancer deaths; first-degree relative