IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-39858-8.html
   My bibliography  Save this article

Androgen receptor binding sites enabling genetic prediction of mortality due to prostate cancer in cancer-free subjects

Author

Listed:
  • Shuji Ito

    (The Laboratory for Statistical and Translational Genetics
    The Laboratory for Bone and Joint Diseases
    Shimane University)

  • Xiaoxi Liu

    (The Laboratory for Statistical and Translational Genetics)

  • Yuki Ishikawa

    (The Laboratory for Statistical and Translational Genetics)

  • David D. Conti

    (University of Southern California)

  • Nao Otomo

    (The Laboratory for Statistical and Translational Genetics
    Keio University)

  • Zsofia Kote-Jarai

    (The Institute of Cancer Research)

  • Hiroyuki Suetsugu

    (The Laboratory for Statistical and Translational Genetics
    Kyushu University)

  • Rosalind A. Eeles

    (The Institute of Cancer Research
    Royal Marsden NHS Foundation Trust)

  • Yoshinao Koike

    (The Laboratory for Statistical and Translational Genetics
    Hokkaido University Graduate School of Medicine)

  • Keiko Hikino

    (The Laboratory for Pharmacogenomics)

  • Soichiro Yoshino

    (The Laboratory for Statistical and Translational Genetics
    Kyushu University)

  • Kohei Tomizuka

    (The Laboratory for Statistical and Translational Genetics)

  • Momoko Horikoshi

    (The Laboratory for Genomics of Diabetes and Metabolism)

  • Kaoru Ito

    (The Cardiovascular Genomics and Informatics)

  • Yuji Uchio

    (Shimane University)

  • Yukihide Momozawa

    (The Laboratory for Genotyping Development)

  • Michiaki Kubo

    (Haradoi Hospital)

  • Yoichiro Kamatani

    (The University of Tokyo)

  • Koichi Matsuda

    (Human Genome Center
    Department of Computational Biology and Medical Sciences)

  • Christopher A. Haiman

    (University of Southern California)

  • Shiro Ikegawa

    (The Laboratory for Bone and Joint Diseases)

  • Hidewaki Nakagawa

    (Laboratory for Cancer Genomics)

  • Chikashi Terao

    (The Laboratory for Statistical and Translational Genetics
    The Clinical Research Center
    The Department of Applied Genetics)

Abstract

Prostate cancer (PrCa) is the second most common cancer worldwide in males. While strongly warranted, the prediction of mortality risk due to PrCa, especially before its development, is challenging. Here, we address this issue by maximizing the statistical power of genetic data with multi-ancestry meta-analysis and focusing on binding sites of the androgen receptor (AR), which has a critical role in PrCa. Taking advantage of large Japanese samples ever, a multi-ancestry meta-analysis comprising more than 300,000 subjects in total identifies 9 unreported loci including ZFHX3, a tumor suppressor gene, and successfully narrows down the statistically finemapped variants compared to European-only studies, and these variants strongly enrich in AR binding sites. A polygenic risk scores (PRS) analysis restricting to statistically finemapped variants in AR binding sites shows among cancer-free subjects, individuals with a PRS in the top 10% have a strongly higher risk of the future death of PrCa (HR: 5.57, P = 4.2 × 10−10). Our findings demonstrate the potential utility of leveraging large-scale genetic data and advanced analytical methods in predicting the mortality of PrCa.

Suggested Citation

  • Shuji Ito & Xiaoxi Liu & Yuki Ishikawa & David D. Conti & Nao Otomo & Zsofia Kote-Jarai & Hiroyuki Suetsugu & Rosalind A. Eeles & Yoshinao Koike & Keiko Hikino & Soichiro Yoshino & Kohei Tomizuka & Mo, 2023. "Androgen receptor binding sites enabling genetic prediction of mortality due to prostate cancer in cancer-free subjects," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39858-8
    DOI: 10.1038/s41467-023-39858-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-39858-8
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-023-39858-8?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Kornelia Polyak & Yong Xia & Jay L. Zweier & Kenneth W. Kinzler & Bert Vogelstein, 1997. "A model for p53-induced apoptosis," Nature, Nature, vol. 389(6648), pages 300-305, September.
    2. Ryo Takata & Atsushi Takahashi & Masashi Fujita & Yukihide Momozawa & Edward J. Saunders & Hiroki Yamada & Kazuhiro Maejima & Kaoru Nakano & Yuichiro Nishida & Asahi Hishida & Keitaro Matsuo & Kenji W, 2019. "12 new susceptibility loci for prostate cancer identified by genome-wide association study in Japanese population," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    3. Meilin Wang & Atsushi Takahashi & Fang Liu & Dingwei Ye & Qiang Ding & Chao Qin & Changjun Yin & Zhengdong Zhang & Koichi Matsuda & Michiaki Kubo & Rong Na & Xiaoling Lin & Haowen Jiang & Shancheng Re, 2015. "Large-scale association analysis in Asians identifies new susceptibility loci for prostate cancer," Nature Communications, Nature, vol. 6(1), pages 1-7, December.
    4. Tunç Morova & Daniel R. McNeill & Nada Lallous & Mehmet Gönen & Kush Dalal & David M. Wilson & Attila Gürsoy & Özlem Keskin & Nathan A. Lack, 2020. "Androgen receptor-binding sites are highly mutated in prostate cancer," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    5. Chikashi Terao & Akari Suzuki & Yukihide Momozawa & Masato Akiyama & Kazuyoshi Ishigaki & Kazuhiko Yamamoto & Koichi Matsuda & Yoshinori Murakami & Steven A. McCarroll & Michiaki Kubo & Po-Ru Loh & Yo, 2020. "Chromosomal alterations among age-related haematopoietic clones in Japan," Nature, Nature, vol. 584(7819), pages 130-135, August.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Yuki Ishikawa & Nao Tanaka & Yoshihide Asano & Masanari Kodera & Yuichiro Shirai & Mitsuteru Akahoshi & Minoru Hasegawa & Takashi Matsushita & Kazuyoshi Saito & Sei-ichiro Motegi & Hajime Yoshifuji & , 2024. "GWAS for systemic sclerosis identifies six novel susceptibility loci including one in the Fcγ receptor region," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Yash Pershad & Taralynn Mack & Hannah Poisner & Yasminka A. Jakubek & Adrienne M. Stilp & Braxton D. Mitchell & Joshua P. Lewis & Eric Boerwinkle & Ruth J. F. Loos & Nathalie Chami & Zhe Wang & Kathle, 2024. "Determinants of mosaic chromosomal alteration fitness," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    2. Arielle S. Strasser & Ana Silvia Gonzalez-Reiche & Xianxiao Zhou & Braulio Valdebenito-Maturana & Xiaoqian Ye & Bin Zhang & Meng Wu & Harm Bakel & Ethylin Wang Jabs, 2024. "Limb reduction in an Esco2 cohesinopathy mouse model is mediated by p53-dependent apoptosis and vascular disruption," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    3. Kelly L. Bolton & Youngil Koh & Michael B. Foote & Hogune Im & Justin Jee & Choong Hyun Sun & Anton Safonov & Ryan Ptashkin & Joon Ho Moon & Ji Yeon Lee & Jongtak Jung & Chang Kyung Kang & Kyoung-Ho S, 2021. "Clonal hematopoiesis is associated with risk of severe Covid-19," Nature Communications, Nature, vol. 12(1), pages 1-8, December.
    4. Jeroen Kneppers & Tesa M. Severson & Joseph C. Siefert & Pieter Schol & Stacey E. P. Joosten & Ivan Pak Lok Yu & Chia-Chi Flora Huang & Tunç Morova & Umut Berkay Altıntaş & Claudia Giambartolomei & Ji, 2022. "Extensive androgen receptor enhancer heterogeneity in primary prostate cancers underlies transcriptional diversity and metastatic potential," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39858-8. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.