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Association of variations in HLA class II and other loci with susceptibility to EGFR-mutated lung adenocarcinoma

Author

Listed:
  • Kouya Shiraishi

    (National Cancer Center Research Institute)

  • Yukinori Okada

    (Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University
    Osaka University Graduate School of Medicine
    Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences)

  • Atsushi Takahashi

    (Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences
    Omics Research Center, National Cerebral and Cardiovascular Center)

  • Yoichiro Kamatani

    (Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences)

  • Yukihide Momozawa

    (Laboratory for Genotyping Development, Center for Integrative Medical Sciences, RIKEN)

  • Kyota Ashikawa

    (Laboratory for Genotyping Development, Center for Integrative Medical Sciences, RIKEN)

  • Hideo Kunitoh

    (Japanese Red Cross Medical Center)

  • Shingo Matsumoto

    (Exploratory Oncology Research and Clinical Trial Center (EPOC), National Cancer Center Research Institute)

  • Atsushi Takano

    (Center for Antibody and Vaccine Therapy, Research Hospital, Institute of Medical Science, The University of Tokyo
    Shiga University of Medical Science)

  • Kimihiro Shimizu

    (Gunma University Hospital)

  • Akiteru Goto

    (Graduate School of Medicine, Akita University)

  • Koji Tsuta

    (National Cancer Center Hospital
    Kansai Medical University)

  • Shun-ichi Watanabe

    (National Cancer Centre Hospital)

  • Yuichiro Ohe

    (National Cancer Center Hospital)

  • Yukio Watanabe

    (National Cancer Centre Hospital)

  • Yasushi Goto

    (National Cancer Center Hospital)

  • Hiroshi Nokihara

    (National Cancer Center Hospital)

  • Koh Furuta

    (National Cancer Center Hospital
    Kanagawa Cancer Center)

  • Akihiko Yoshida

    (National Cancer Center Hospital)

  • Koichi Goto

    (National Cancer Center Hospital East)

  • Tomoyuki Hishida

    (National Cancer Center Hospital East)

  • Masahiro Tsuboi

    (National Cancer Center Hospital East)

  • Katsuya Tsuchihara

    (Exploratory Oncology Research and Clinical Trial Center (EPOC), National Cancer Center Research Institute)

  • Yohei Miyagi

    (Kanagawa Cancer Center Research Institute)

  • Haruhiko Nakayama

    (Kanagawa Cancer Center)

  • Tomoyuki Yokose

    (Kanagawa Cancer Center)

  • Kazumi Tanaka

    (Gunma University Hospital)

  • Toshiteru Nagashima

    (Gunma University Hospital)

  • Yoichi Ohtaki

    (Gunma University Hospital)

  • Daichi Maeda

    (Graduate School of Medicine, Akita University)

  • Kazuhiro Imai

    (Graduate School of Medicine, Akita University)

  • Yoshihiro Minamiya

    (Graduate School of Medicine, Akita University)

  • Hiromi Sakamoto

    (National Cancer Center Research Institute)

  • Akira Saito

    (StaGen Co., Ltd.)

  • Yoko Shimada

    (National Cancer Center Research Institute)

  • Kuniko Sunami

    (National Cancer Center Research Institute
    National Cancer Center Hospital)

  • Motonobu Saito

    (National Cancer Center Research Institute)

  • Johji Inazawa

    (Medical Research Institute, Tokyo Medical and Dental University
    Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University
    Bioresource Research Center, Tokyo Medical and Dental University)

  • Yusuke Nakamura

    (Center for Personalized Therapeutics, The University of Chicago)

  • Teruhiko Yoshida

    (National Cancer Center Research Institute)

  • Jun Yokota

    (Genomics and Epigenomics of Cancer Prediction Program, Institute of Predictive and Personalized Medicine of Cancer (IMPPC))

  • Fumihiko Matsuda

    (Center for Genomic Medicine, Graduate School of Medicine, Kyoto University)

  • Keitaro Matsuo

    (Aichi Cancer Center Research Institute)

  • Yataro Daigo

    (Center for Antibody and Vaccine Therapy, Research Hospital, Institute of Medical Science, The University of Tokyo
    Shiga University of Medical Science)

  • Michiaki Kubo

    (Laboratory for Genotyping Development, Center for Integrative Medical Sciences, RIKEN)

  • Takashi Kohno

    (National Cancer Center Research Institute)

Abstract

Lung adenocarcinoma driven by somatic EGFR mutations is more prevalent in East Asians (30–50%) than in European/Americans (10–20%). Here we investigate genetic factors underlying the risk of this disease by conducting a genome-wide association study, followed by two validation studies, in 3,173 Japanese patients with EGFR mutation-positive lung adenocarcinoma and 15,158 controls. Four loci, 5p15.33 (TERT), 6p21.3 (BTNL2), 3q28 (TP63) and 17q24.2 (BPTF), previously shown to be strongly associated with overall lung adenocarcinoma risk in East Asians, were re-discovered as loci associated with a higher susceptibility to EGFR mutation-positive lung adenocarcinoma. In addition, two additional loci, HLA class II at 6p21.32 (rs2179920; P =5.1 × 10−17, per-allele OR=1.36) and 6p21.1 (FOXP4) (rs2495239; P=3.9 × 10−9, per-allele OR=1.19) were newly identified as loci associated with EGFR mutation-positive lung adenocarcinoma. This study indicates that multiple genetic factors underlie the risk of lung adenocarcinomas with EGFR mutations.

Suggested Citation

  • Kouya Shiraishi & Yukinori Okada & Atsushi Takahashi & Yoichiro Kamatani & Yukihide Momozawa & Kyota Ashikawa & Hideo Kunitoh & Shingo Matsumoto & Atsushi Takano & Kimihiro Shimizu & Akiteru Goto & Ko, 2016. "Association of variations in HLA class II and other loci with susceptibility to EGFR-mutated lung adenocarcinoma," Nature Communications, Nature, vol. 7(1), pages 1-7, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12451
    DOI: 10.1038/ncomms12451
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    Cited by:

    1. Jianxin Shi & Kouya Shiraishi & Jiyeon Choi & Keitaro Matsuo & Tzu-Yu Chen & Juncheng Dai & Rayjean J. Hung & Kexin Chen & Xiao-Ou Shu & Young Tae Kim & Maria Teresa Landi & Dongxin Lin & Wei Zheng & , 2023. "Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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