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A full genome scan for gastric cancer
  1. M Aoki1,
  2. K Yamamoto1,
  3. H Noshiro3,
  4. K Sakai1,
  5. J Yokota4,
  6. T Kohno4,
  7. T Tokino5,
  8. S Ishida5,
  9. S Ohyama6,
  10. I Ninomiya7,
  11. K Uesaka8,
  12. M Kitajima9,
  13. S Shimada10,
  14. S Matsuno11,
  15. M Yano12,
  16. M Hiratsuka13,
  17. H Sugimura14,
  18. F Itoh15,
  19. T Minamoto16,
  20. Y Maehara17,
  21. S Takenoshita18,
  22. T Aikou19,
  23. H Katai20,
  24. K Yoshimura21,
  25. T Takahashi22,
  26. K Akagi23,
  27. M Sairenji24,
  28. Y Yamamura2,
  29. T Sasazuki25
  1. 1Division of Molecular Population Genetics, Department of Molecular Genetics, Medical Institute of Bioregulation and COE Program on Lifestyle-Related Diseases, Kyushu University, Fukuoka, Japan
  2. 2Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya, Japan
  3. 3Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
  4. 4Biology Division, National Cancer Center Research Institute, Tokyo, Japan
  5. 5Department of Molecular Biology, Cancer Research Institute, School of Medicine, Sapporo Medical University, Sapporo, Japan
  6. 6Department of GI Surgery, Cancer Institute Hospital, Tokyo, Japan
  7. 7Gastroenterologic Surgery, Department of Oncology, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan
  8. 8Surgical Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan
  9. 9Department of Surgery, School of Medicine, Keio University, Tokyo, Japan
  10. 10Second Department of Surgery, Kumamoto University School of Medicine, Kumamoto, Japan
  11. 11First Department of Surgery, Tohoku University School of Medicine, Sendai, Japan
  12. 12Department of Surgery and Clinical Oncology, Graduate School of Medicine, Osaka University, Osaka, Japan
  13. 13Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan
  14. 14Department of Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan
  15. 15Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan
  16. 16Division of Diagnostic Molecular Oncology and Surgical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan
  17. 17Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
  18. 18Second Department of Surgery, Fukushima Medical University, Fukushima, Japan
  19. 19First Department of Surgery, Kagoshima University School of Medicine, Kagoshima, Japan
  20. 20National Cancer Center Hospital, Tokyo, Japan
  21. 21Cancer Information and Epidemiology Division, National Cancer Center Research Institute, Tokyo, Japan
  22. 22Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
  23. 23Saitama Cancer Center Research Institute, Saitama, Japan
  24. 24Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
  25. 25International Medical Center of Japan, Tokyo, Japan
  1. Correspondence to:
 Takehiko Sasazuki
 International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan; sasazukinciryo.hosp.go.jp

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It is generally accepted that multiple factors play a role in gastric carcinogenesis, including diet,1,2 lifestyle,3 infectious agents such as Helicobacter pylori (H. pylori),4,5 and genetic factors as well as gene-environment interactions.6,7 Although the continuous decrease in the incidence of gastric cancer in recent decades can be explained by changing lifestyle, diet habits, and reduced H. pylori infection, the fact that some individuals develop gastric cancer while others do not under similar environmental exposures suggests that genetic predisposition plays an important role in the pathogenesis of this disease. In addition, familial clustering of cases of gastric cancer, a higher incidence of the disease among the relatives of patients than among matched controls, and a more common coincidence of the disease in homozygotic than in heterozygotic twins, also supports genetic links with gastric cancer.8,9,10

In contrast with the vast amount of accumulated information on environmental factors, little is known about the genetic factors linked to gastric cancer. Several studies have reported disease susceptible loci for gastric cancer, based on association analysis of candidate genes involved in DNA repair, detoxification, or the immune system.11 Studies on familial clustering of gastric cancer revealed germline mutations in CDH1, ATM, and MET.12–14 In addition, gastric cancer frequently occurs in family members with monogenic diseases such as hereditary non-polyposis colorectal cancer, Li-Fraumeni syndrome, familial adenomatous polyposis, and Peutz-Jeghers syndrome.15–18 However, these polymorphisms and/or mutations cannot explain the overall genetic components of gastric cancer.

It is now feasible to screen the entire human genome for genes exerting a major effect on susceptibility to multifactorial diseases. Because gastric cancer, like many complex diseases, exhibits genetic heterogeneity, we carried out a genome-wide linkage study to search for possible susceptibility loci related to gastric …

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