Open Access

Nature Communications

, volume 11 , issue 1 , publication number 3175

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

Yingsong Lin ¹

Masahiro Nakatochi ^{2, 3}

Yasuyuki Hosono ⁴

Hidemi Ito ^{5, 6}

Yoichiro Kamatani ^{7, 8}

Akihito Inoko ^{9, 10}

HIROMI SAKAMOTO ¹¹

Fumie Kinoshita ¹²

Yumiko Kobayashi ¹²

Hiroshi Ishii ¹³

Masato Ozaka ¹⁴

TAKASHI SASAKI ¹⁴

Masato Matsuyama ¹⁴

Naoki Sasahira ¹⁴

Manabu Morimoto ¹⁵

Satoshi Kobayashi ¹⁵

Taito Fukushima ¹⁵

Makoto Ueno ¹⁵

Shinichi Ohkawa ¹⁵

Naoto EGAWA ¹⁶

Sawako Kuruma ¹⁷

MITSURU MORI ¹⁸

Haruhisa Nakao ¹⁹

Yasushi Adachi ²⁰

Masumi Okuda ²¹

Takako Osaki ²²

Shigeru Kamiya ²²

Chaochen Wang ¹

Kazuo Hara ²³

Yasuhiro Shimizu ²⁴

Tatsuo Miyamoto ²⁵

Yuko Hayashi ⁴

Hiromichi Ebi ⁴

Tomohiro Kohmoto ^{26, 27}

Issei Imoto ²⁷

Yumiko Kasugai ^{9, 28}

Yoshinori Murakami ²⁹

Masato Akiyama ^{7, 30}

Kazuyoshi Ishigaki ⁷

Koichi Matsuda ³¹

Makoto Hirata ²⁹

Kazuaki Shimada ³²

Takuji Okusaka ³³

Takahisa Kawaguchi ³⁴

Meiko Takahashi ³⁴

Yoshiyuki Watanabe ³⁵

Kiyonori Kuriki ³⁶

Aya Kadota ³⁷

Rieko Okada ³⁸

Haruo Mikami ³⁹

Toshiro Takezaki ⁴⁰

Sadao SUZUKI ⁴¹

Taiki Yamaji ⁴²

Motoki Iwasaki ⁴²

N. Sawada ⁴²

Atsushi Goto ⁴²

Kengo Kinoshita ⁴³

Nobuo Fuse ⁴³

Fumiki Katsuoka ⁴³

Atsushi Shimizu ⁴⁴

Satoshi Nishizuka ⁴⁴

Kozo Tanno ^{44, 45}

Ken Suzuki ^{7, 46, 47, 48}

Yukinori Okada ^{7, 48, 49}

Momoko Horikoshi ⁴⁷

Toshimasa Yamauchi ⁴⁶

Takashi Kadowaki ⁴⁶

Herbert Yu ⁵⁰

Jun Zhong ⁵¹

Laufey Amundadottir ⁵¹

Yuichiro Doki ⁵²

Hideshi Ishii ⁵³

Hidetoshi Eguchi ⁵²

David D.A. Bogumil ⁵⁴

Christopher A. Haiman ^{54, 55}

Loïc Le Marchand ⁵⁰

Masaki Mori ⁵⁶

Harvey Risch ⁵⁷

Veronica W. Setiawan ^{54, 55}

Shoichiro Tsugane ⁵⁸

Kenji Wakai ³⁸

Teruhiko YOSHIDA ¹¹

Fumihiko Matsuda ³⁴

Michiaki Kubo ⁵⁹

Shogo Kikuchi ¹

K. Matsuo ^{9, 28}

Hide authors affiliations Show authors affiliations: 59 affiliations

Department of Public Health, Aichi Medical University School of Medicine, Nagakute, Japan |

Division of Public Health Informatics, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan |

Department of Nursing, Nagoya University Graduate School of Medicine, Nagoya, Japan |

⁴

Division of Molecular Therapeutics, Aichi Cancer Center Research Institute, Nagoya, Japan |

⁵

Division of Cancer Information and Control, Aichi Cancer Center Research Institute, Nagoya, Japan |

⁶

Department of Descriptive Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan |

⁷

Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan |

⁸

Laboratory of Complex Trait Genomics, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, the University of Tokyo, Tokyo, Japan |

⁹

Division of Cancer Epidemiology and prevention, Aichi Cancer Center Research Institute, Nagoya, Japan |

¹⁰

Department of Pathology, Aichi Medical University School of Medicine, Nagakute, Japan |

¹¹

Genetics Division, National Cancer Center Research Institute, Tokyo, Japan |

¹²

Data Science Division, Data Coordinating Center, Department of Advanced Medicine, Nagoya University Hospital, Nagoya, Japan |

¹³

Chiba Cancer Center, Chiba, Japan |

¹⁴

Department of Hepato-Biliary-Pancreatic Medicine, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan |

¹⁵

Department of Gastroenterology, Hepatobiliary and Pancreatic Medical Oncology Division, Kanagawa Cancer Center, Yokohama, Japan |

¹⁶

Department of Gastroenterology, Tokyo Metropolitan Hiroo Hospital, Tokyo, Japan |

¹⁷

Department of Gastroenterology, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan |

¹⁸

Hokkaido Chitose College of Rehabilitation, Hokkaido, Japan |

¹⁹

Division of Hepatology and Pancreatology, Aichi Medical University School of Medicine, Nagakute, Japan |

²⁰

Sapporo Shirakabadai Hospital, Sapporo, Japan |

²¹

Department of Pediatrics, Hyogo college of Medicine, Nishinomiya, Japan |

²²

Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo, Japan |

²³

Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan |

²⁴

Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya, Japan |

²⁵

Department of Genetics and Cell Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan |

²⁶

Department of Human Genetics, Tokushima University Graduate School of Medicine, Tokushima, Japan |

²⁷

Division of Molecular Genetics, Aichi Cancer Center Research Institute, Nagoya, Japan |

²⁸

Department of Cancer Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan |

²⁹

Division of Molecular Pathology, Institute of Medical Science, the University of Tokyo, Tokyo, Japan |

³⁰

Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu university, Fukuoka, Japan |

³¹

Graduate school of Frontier Sciences, the University of Tokyo, Tokyo, Japan |

³²

Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan |

³³

Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan |

³⁴

Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan |

³⁵

Department of Epidemiology for Community health and Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan |

³⁶

Laboratory of Public Health, School of Food and Nutritional Sciences, University of Shizuoka, Shizuoka, Japan |

³⁷

Department of Public Health, Shiga University of Medical Science, Otsu, Japan |

³⁸

Department of Preventive medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan |

³⁹

Cancer Prevention Center, Chiba Cancer Center Research Institute, Chiba, Japan |

⁴⁰

Department of International Island and Community Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan |

⁴¹

Department of Public Health, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan |

⁴²

Division of Epidemiology, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan |

⁴³

Tohoku Medical Megabank organization, Tohoku University, Sendai, Japan |

⁴⁴

Iwate Tohoku Medical Megabank Organization, Iwate Medical University, Iwate, Japan |

⁴⁵

Department of Hygiene and Preventive Medicine, School of Medicine, Iwate Medicalm University, Iwate, Japan |

⁴⁶

Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan |

⁴⁷

Laboratory for Endocrinology, Metabolism and Kidney Diseases, RIKEN Centre for Integrative Medical Sciences, Yokohama, Japan |

⁴⁸

Department of Statistical Genetics, Osaka University Graduate School of Medicine, Osaka, Japan |

⁴⁹

Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Osaka, Japan |

⁵⁰

University of Hawaii cancer Center, Honolulu, USA |

⁵¹

Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, USA |

⁵²

Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan |

⁵³

Department of Medical Data Science, Graduate School of Medicine, Osaka University, Osaka, Japan |

⁵⁴

Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeless, CA, USA |

⁵⁵

Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, USA |

⁵⁶

Department of Surgery and Science, Graduate school of Medical Sciences, Kyushu University, Fukuoka, Japan |

⁵⁷

Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, USA |

⁵⁸

Center for Public Health Sciences, National Cancer Center, Tokyo, Japan |

⁵⁹

RIKEN Center for Integrative Medical Sciences, Yokohama, Japan |

Publication type: Journal Article

Publication date: 2020-06-24

Springer Nature

Nature Communications

scimago Q1

wos Q1

SJR: 4.761

CiteScore: 23.4

Impact factor: 15.7

ISSN: 20411723

DOI: 10.1038/s41467-020-16711-w

Copy DOI

PubMed ID: 32581250

General Chemistry

General Biochemistry, Genetics and Molecular Biology

General Physics and Astronomy

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. Previous genome-wide association studies have identified risk loci for pancreatic cancer but were centered on individuals of European ancestry. Here the authors identify GP2 gene variants associated with pancreatic cancer susceptibility in populations of East Asian ancestry.

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Lin Y. et al. Genome-wide association meta-analysis identifies GP2 gene risk variants for pancreatic cancer // Nature Communications. 2020. Vol. 11. No. 1. 3175

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Lin Y. et al. Genome-wide association meta-analysis identifies GP2 gene risk variants for pancreatic cancer // Nature Communications. 2020. Vol. 11. No. 1. 3175

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@article{2020_Lin,

author = {Yingsong Lin and Masahiro Nakatochi and Yasuyuki Hosono and Hidemi Ito and Yoichiro Kamatani and Akihito Inoko and HIROMI SAKAMOTO and Fumie Kinoshita and Yumiko Kobayashi and Hiroshi Ishii and Masato Ozaka and TAKASHI SASAKI and Masato Matsuyama and Naoki Sasahira and Manabu Morimoto and Satoshi Kobayashi and Taito Fukushima and Makoto Ueno and Shinichi Ohkawa and Naoto EGAWA and Sawako Kuruma and MITSURU MORI and Haruhisa Nakao and Yasushi Adachi and Masumi Okuda and Takako Osaki and Shigeru Kamiya and Chaochen Wang and Kazuo Hara and Yasuhiro Shimizu and Tatsuo Miyamoto and Yuko Hayashi and Hiromichi Ebi and Tomohiro Kohmoto and Issei Imoto and Yumiko Kasugai and Yoshinori Murakami and Masato Akiyama and Kazuyoshi Ishigaki and Koichi Matsuda and Makoto Hirata and Kazuaki Shimada and Takuji Okusaka and Takahisa Kawaguchi and Meiko Takahashi and Yoshiyuki Watanabe and Kiyonori Kuriki and Aya Kadota and Rieko Okada and Haruo Mikami and others},

title = {Genome-wide association meta-analysis identifies GP2 gene risk variants for pancreatic cancer},

journal = {Nature Communications},

year = {2020},

volume = {11},

publisher = {Springer Nature},

month = {jun},

url = {https://doi.org/10.1038/s41467-020-16711-w},

number = {1},

pages = {3175},

doi = {10.1038/s41467-020-16711-w}

}

Publisher

Springer Nature

Journal

Nature Communications

scimago Q1

wos Q1

SJR

4.761

CiteScore

23.4

Impact factor

15.7

ISSN

20411723 (Print, Electronic)