Genome-wide association meta-analysis identifies GP2 gene risk variants for pancreatic cancer View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2020-06-24

AUTHORS

Yingsong Lin, Masahiro Nakatochi, Yasuyuki Hosono, Hidemi Ito, Yoichiro Kamatani, Akihito Inoko, Hiromi Sakamoto, Fumie Kinoshita, Yumiko Kobayashi, Hiroshi Ishii, Masato Ozaka, Takashi Sasaki, Masato Matsuyama, Naoki Sasahira, Manabu Morimoto, Satoshi Kobayashi, Taito Fukushima, Makoto Ueno, Shinichi Ohkawa, Naoto Egawa, Sawako Kuruma, Mitsuru Mori, Haruhisa Nakao, Yasushi Adachi, Masumi Okuda, Takako Osaki, Shigeru Kamiya, Chaochen Wang, Kazuo Hara, Yasuhiro Shimizu, Tatsuo Miyamoto, Yuko Hayashi, Hiromichi Ebi, Tomohiro Kohmoto, Issei Imoto, Yumiko Kasugai, Yoshinori Murakami, Masato Akiyama, Kazuyoshi Ishigaki, Koichi Matsuda, Makoto Hirata, Kazuaki Shimada, Takuji Okusaka, Takahisa Kawaguchi, Meiko Takahashi, Yoshiyuki Watanabe, Kiyonori Kuriki, Aya Kadota, Rieko Okada, Haruo Mikami, Toshiro Takezaki, Sadao Suzuki, Taiki Yamaji, Motoki Iwasaki, Norie Sawada, Atsushi Goto, Kengo Kinoshita, Nobuo Fuse, Fumiki Katsuoka, Atsushi Shimizu, Satoshi S. Nishizuka, Kozo Tanno, Ken Suzuki, Yukinori Okada, Momoko Horikoshi, Toshimasa Yamauchi, Takashi Kadowaki, Herbert Yu, Jun Zhong, Laufey T. Amundadottir, Yuichiro Doki, Hideshi Ishii, Hidetoshi Eguchi, David Bogumil, Christopher A. Haiman, Loic Le Marchand, Masaki Mori, Harvey Risch, Veronica W. Setiawan, Shoichiro Tsugane, Kenji Wakai, Teruhiko Yoshida, Fumihiko Matsuda, Michiaki Kubo, Shogo Kikuchi, Keitaro Matsuo

ABSTRACT

Pancreatic cancer is the fourth leading cause of cancer-related deaths in Japan. To identify risk loci, we perform a meta-analysis of three genome-wide association studies comprising 2,039 pancreatic cancer patients and 32,592 controls in the Japanese population. Here, we identify 3 (13q12.2, 13q22.1, and 16p12.3) genome-wide significant loci (P < 5.0 × 10−8), of which 16p12.3 has not been reported in the Western population. The lead single nucleotide polymorphism (SNP) at 16p12.3 is rs78193826 (odds ratio = 1.46, 95% confidence interval = 1.29-1.66, P = 4.28 × 10−9), an Asian-specific, nonsynonymous glycoprotein 2 (GP2) gene variant. Associations between selected GP2 gene variants and pancreatic cancer are replicated in 10,822 additional cases and controls of East Asian origin. Functional analyses using cell lines provide supporting evidence of the effect of rs78193826 on KRAS activity. These findings suggest that GP2 gene variants are probably associated with pancreatic cancer susceptibility in populations of East Asian ancestry. More... »

PAGES

3175

References to SciGraph publications

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  • Journal

    TITLE

    Nature Communications

    ISSUE

    1

    VOLUME

    11

    Author Affiliations

  • Department of Public Health, Aichi Medical University School of Medicine, 480-1195, Nagakute, Aichi, Japan
  • Department of Nursing, Nagoya University Graduate School of Medicine, 461-8673, Nagoya, Japan
  • Division of Molecular Therapeutics, Aichi Cancer Center Research Institute, 464-8681, Nagoya, Japan
  • Department of Descriptive Epidemiology, Nagoya University Graduate School of Medicine, 466-8550, Nagoya, Japan
  • Laboratory of Complex Trait Genomics, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 108-8639, Tokyo, Japan
  • Department of Pathology, Aichi Medical University School of Medicine, 480-1195, Nagakute, Japan
  • Genetics Division, National Cancer Center Research Institute, 104-0045, Tokyo, Japan
  • Data Science Division, Data Coordinating Center, Department of Advanced Medicine, Nagoya University Hospital, 461-8673, Nagoya, Japan
  • Chiba Cancer Center, 260-8717, Chiba, Japan
  • Department of Hepato-biliary-pancreatic Medicine, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 135-8550, Tokyo, Japan
  • Department of Gastroenterology, Hepatobiliary and Pancreatic Medical Oncology Division, Kanagawa Cancer Center, 241-8515, Yokohama, Japan
  • Department of Gastroenterology, Tokyo Metropolitan Hiroo Hospital, 150-0013, Tokyo, Japan
  • Department of Gastroenterology, Tokyo Metropolitan Komagome Hospital, 113-8677, Tokyo, Japan
  • Hokkaido Chitose College of Rehabilitation, 066-0055, Hokkaido, Japan
  • Division of Hepatology and Pancreatology, Aichi Medical University School of Medicine, 480-1195, Nagakute, Japan
  • Sapporo Shirakabadai Hospital, 062-0052, Sapporo, Japan
  • Department of Pediatrics, Hyogo College of Medicine, 663-8501, Nishinomiya, Hyogo, Japan
  • Department of Infectious Diseases, Kyorin University School of Medicine, 181-8611, Tokyo, Japan
  • Department of Gastroenterology, Aichi Cancer Center Hospital, 464-8681, Nagoya, Japan
  • Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, 464-8681, Nagoya, Japan
  • Department of Genetics and Cell Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 734-8553, Hiroshima, Japan
  • Division of Molecular Genetics, Aichi Cancer Center Research Institute, 464-8681, Nagoya, Japan
  • Department of Cancer Epidemiology, Nagoya University Graduate School of Medicine, 466-8550, Nagoya, Japan
  • Division of Molecular Pathology, Institute of Medical Science, The University of Tokyo, 108-8639, Tokyo, Japan
  • Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, 812-8582, Fukuoka, Japan
  • Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, 230-0045, Yokohama, Japan
  • Graduate School of Frontier Sciences, The University of Tokyo, 108-8639, Tokyo, Japan
  • Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, 104-0045, Tokyo, Japan
  • Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, 104-0045, Tokyo, Japan
  • Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, 606-8501, Kyoto, Japan
  • Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, 602-8566, Kyoto, Japan
  • Laboratory of Public Health, School of Food and Nutritional Sciences, University of Shizuoka, 422-8526, Shizuoka, Japan
  • Department of Public Health, Shiga University of Medical Science, 520-2192, Otsu, Japan
  • Department of Preventive Medicine, Nagoya University Graduate School of Medicine, 466-8550, Nagoya, Japan
  • Cancer Prevention Center, Chiba Cancer Center Research Institute, 260-8717, Chiba, Japan
  • Department of International Island and Community Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 890-8544, Kagoshima, Japan
  • Department of Public Health, Nagoya City University Graduate School of Medical Sciences, 467-8601, Nagoya, Japan
  • Division of Epidemiology, Center for Public Health Sciences, National Cancer Center, 104-0045, Tokyo, Japan
  • Tohoku Medical Megabank Organization, Tohoku University, 980-8573, Sendai, Japan
  • Iwate Tohoku Medical Megabank Organization, Iwate Medical University, 028-3694, Iwate, Japan
  • Department of Hygiene and Preventive Medicine, School of Medicine, Iwate Medicalm University, 028-3694, Iwate, Japan
  • Department of Statistical Genetics, Osaka University Graduate School of Medicine, 565-0871, Osaka, Japan
  • Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, 565-0871, Osaka, Japan
  • Laboratory for Endocrinology, Metabolism and Kidney Diseases, RIKEN Centre for Integrative Medical Sciences, 230-0045, Yokohama, Japan
  • Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, 113-0033, Tokyo, Japan
  • University of Hawaii Cancer Center, 96813, Honolulu, HI, USA
  • Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 20892, Bethesda, MD, USA
  • Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 565-0871, Osaka, Japan
  • Department of Medical Data Science, Graduate School of Medicine, Osaka University, 565-0871, Osaka, Japan
  • Department of Preventive Medicine, Keck School of Medicine, University of Southern California, 90033, Los Angeless, CA, USA
  • Norris Comprehensive Cancer Center, University of Southern California, 90033, Los Angeles, CA, USA
  • Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 812-8582, Fukuoka, Japan
  • Department of Chronic Disease Epidemiology, Yale School of Public Health, 06520, New Haven, CT, USA
  • Center for Public Health Sciences, National Cancer Center, 104-0045, Tokyo, Japan
  • RIKEN Center for Integrative Medical Sciences, 230-0045, Yokohama, Japan
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-020-16711-w

    DOI

    http://dx.doi.org/10.1038/s41467-020-16711-w

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1128715386

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/32581250


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