Causes of Cancer Death Among First-Degree Relatives in Japanese Families with Lynch Syndrome

Kohji Tanakaya; Tatsuro Yamaguchi; Hideki Ishikawa; Takao Hinoi; Yoichi Furukawa; Keiji Hirata; Yoshihisa Saida; Mototsugu Shimokawa; Masami Arai; Nagahide Matsubara; Naohiro Tomita; Kazuo Tamura; Kokichi Sugano; Chikashi Ishioka; Teruhiko Yoshida; Hideyuki Ishida; Toshiaki Watanabe; Kenichi Sugihara; for HNPCC Registry and Genetic Testing Project of the Japanese Society for Cancer of the Colon and Rectum

Causes of Cancer Death Among First-Degree Relatives in Japanese Families with Lynch Syndrome

Anticancer Res. 2016 Apr;36(4):1985-9.

Authors

Kohji Tanakaya¹, Tatsuro Yamaguchi², Hideki Ishikawa³, Takao Hinoi⁴, Yoichi Furukawa⁵, Keiji Hirata⁶, Yoshihisa Saida⁷, Mototsugu Shimokawa⁸, Masami Arai⁹, Nagahide Matsubara¹⁰, Naohiro Tomita¹⁰, Kazuo Tamura¹¹, Kokichi Sugano¹², Chikashi Ishioka¹³, Teruhiko Yoshida¹⁴, Hideyuki Ishida¹⁵, Toshiaki Watanabe¹⁶, Kenichi Sugihara¹⁷; for HNPCC Registry and Genetic Testing Project of the Japanese Society for Cancer of the Colon and Rectum

Affiliations

¹ Department of Surgery, Iwakuni Clinical Center, Iwakuni, Japan.
² Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan.
³ Department of Molecular-Targeting Cancer Prevention, Kyoto Prefectural University of Medicine, Kyoto, Japan.
⁴ Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
⁵ Division of Clinical Genome Research, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
⁶ Department of Surgery 1, University of Occupational and Environmental Health, Kitakyushu, Japan.
⁷ Department of Surgery, Toho University Ohashi Medical Center, Tokyo, Japan.
⁸ Clinical Research Institute, National Kyushu Cancer Center, Fukuoka, Japan.
⁹ Clinical Genetic Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
¹⁰ Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan.
¹¹ Major in Science, Graduate School of Science and Engineering Research, Kinki University, Higashiosaka, Japan.
¹² Oncogene Research Unit/Cancer Prevention Unit, Tochigi Cancer Center, Utsunomiya, Japan.
¹³ Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
¹⁴ Genetics Division, National Cancer Center Research Institute, Tokyo, Japan.
¹⁵ Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Kawagoe, Japan [email protected].
¹⁶ Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan.
¹⁷ Tokyo Medical and Dental University, Tokyo, Japan.

PMID: 27069191

Abstract

Aim: 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).

Conclusion: 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.

Keywords: Japan; Lynch syndrome; causes of cancer deaths; first-degree relative.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing / genetics
Adult
Aged
Aged, 80 and over
Asian People / genetics
Biliary Tract Neoplasms / genetics
Biliary Tract Neoplasms / mortality
Cause of Death
Colonic Neoplasms / genetics
Colonic Neoplasms / mortality
Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
Colorectal Neoplasms, Hereditary Nonpolyposis / mortality*
DNA-Binding Proteins / genetics
Family
Female
Genetic Predisposition to Disease
Germ-Line Mutation
Humans
Male
Middle Aged
MutL Protein Homolog 1
MutS Homolog 2 Protein / genetics*
Nuclear Proteins / genetics
Ovarian Neoplasms / genetics
Ovarian Neoplasms / mortality
Risk Factors
Stomach Neoplasms / genetics
Stomach Neoplasms / mortality
Uterine Neoplasms / genetics
Uterine Neoplasms / mortality

Substances

Adaptor Proteins, Signal Transducing
DNA-Binding Proteins
G-T mismatch-binding protein
MLH1 protein, human
Nuclear Proteins
MSH2 protein, human
MutL Protein Homolog 1
MutS Homolog 2 Protein