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Identification of 22 susceptibility loci associated with testicular germ cell tumors

Author

Listed:
  • John Pluta

    (University of Pennsylvania)

  • Louise C. Pyle

    (Children’s Hospital of Philadelphia)

  • Kevin T. Nead

    (University of Pennsylvania)

  • Rona Wilf

    (University of Pennsylvania)

  • Mingyao Li

    (University of Pennsylvania)

  • Nandita Mitra

    (University of Pennsylvania)

  • Benita Weathers

    (University of Pennsylvania)

  • Kurt D’Andrea

    (University of Pennsylvania)

  • Kristian Almstrup

    (Rigshospitalet)

  • Lynn Anson-Cartwright

    (University of Toronto and The Princess Margaret Cancer Centre)

  • Javier Benitez

    (Spanish National Cancer Centre (CNIO))

  • Christopher D. Brown

    (University of Pennsylvania)

  • Stephen Chanock

    (National Cancer Institute)

  • Chu Chen

    (University of Washington)

  • Victoria K. Cortessis

    (Keck School of Medicine at the University of Southern California)

  • Alberto Ferlin

    (University of Brescia)

  • Carlo Foresta

    (University of Padova)

  • Marija Gamulin

    (University Hospital Centre Zagreb, University of Zagreb School of Medicine)

  • Jourik A. Gietema

    (University Medical Center Groningen, University of Groningen)

  • Chiara Grasso

    (University of Turin and CPO-Piemonte)

  • Mark H. Greene

    (National Cancer Institute)

  • Tom Grotmol

    (Cancer Registry of Norway)

  • Robert J. Hamilton

    (University of Toronto and The Princess Margaret Cancer Centre)

  • Trine B. Haugen

    (Faculty of Health Sciences, OsloMet—Oslo Metropolitan University)

  • Russ Hauser

    (Harvard T.H. Chan School of Public Health)

  • Michelle A. T. Hildebrandt

    (University of Texas MD Anderson Cancer Center)

  • Matthew E. Johnson

    (Children’s Hospital of Philadelphia
    Children’s Hospital of Philadelphia)

  • Robert Karlsson

    (Karolinska Institutet)

  • Lambertus A. Kiemeney

    (Radboud University Medical Center)

  • Davor Lessel

    (University Medical Center Hamburg-Eppendorf)

  • Ragnhild A. Lothe

    (Oslo University Hospital-Radiumhospitalet
    University of Oslo)

  • Jennifer T. Loud

    (National Cancer Institute)

  • Chey Loveday

    (The Institute of Cancer Research)

  • Paloma Martin-Gimeno

    (Spanish National Cancer Centre (CNIO))

  • Coby Meijer

    (University Medical Center Groningen, University of Groningen)

  • Jérémie Nsengimana

    (Newcastle University)

  • David I. Quinn

    (Division of Oncology, Keck School of Medicine at the University of Southern California)

  • Thorunn Rafnar

    (deCODE Genetics/Amgen)

  • Shweta Ramdas

    (University of Pennsylvania)

  • Lorenzo Richiardi

    (University of Turin and CPO-Piemonte)

  • Rolf I. Skotheim

    (Oslo University Hospital-Radiumhospitalet
    University of Oslo)

  • Kari Stefansson

    (deCODE Genetics/Amgen)

  • Clare Turnbull

    (University of Oslo
    Queen Mary University)

  • David J. Vaughn

    (University of Pennsylvania
    University of Pennsylvania)

  • Fredrik Wiklund

    (Karolinska Institutet)

  • Xifeng Wu

    (Zhejiang University)

  • Daphne Yang

    (University of Pennsylvania)

  • Tongzhang Zheng

    (Brown University)

  • Andrew D. Wells

    (Children’s Hospital of Philadelphia
    University of Pennsylvania)

  • Struan F. A. Grant

    (Children’s Hospital of Philadelphia
    University of Pennsylvania
    Children’s Hospital of Philadelphia)

  • Ewa Rajpert-De Meyts

    (Rigshospitalet)

  • Stephen M. Schwartz

    (University of Washington)

  • D. Timothy Bishop

    (University of Leeds)

  • Katherine A. McGlynn

    (National Cancer Institute)

  • Peter A. Kanetsky

    (H. Lee Moffitt Cancer Center and Research Institute)

  • Katherine L. Nathanson

    (University of Pennsylvania
    University of Pennsylvania)

Abstract

Testicular germ cell tumors (TGCT) are the most common tumor in young white men and have a high heritability. In this study, the international Testicular Cancer Consortium assemble 10,156 and 179,683 men with and without TGCT, respectively, for a genome-wide association study. This meta-analysis identifies 22 TGCT susceptibility loci, bringing the total to 78, which account for 44% of disease heritability. Men with a polygenic risk score (PRS) in the 95th percentile have a 6.8-fold increased risk of TGCT compared to men with median scores. Among men with independent TGCT risk factors such as cryptorchidism, the PRS may guide screening decisions with the goal of reducing treatment-related complications causing long-term morbidity in survivors. These findings emphasize the interconnected nature of two known pathways that promote TGCT susceptibility: male germ cell development within its somatic niche and regulation of chromosomal division and structure, and implicate an additional biological pathway, mRNA translation.

Suggested Citation

  • John Pluta & Louise C. Pyle & Kevin T. Nead & Rona Wilf & Mingyao Li & Nandita Mitra & Benita Weathers & Kurt D’Andrea & Kristian Almstrup & Lynn Anson-Cartwright & Javier Benitez & Christopher D. Bro, 2021. "Identification of 22 susceptibility loci associated with testicular germ cell tumors," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24334-y
    DOI: 10.1038/s41467-021-24334-y
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    Cited by:

    1. Yaohua Yang & Yaxin Chen & Shuai Xu & Xingyi Guo & Guochong Jia & Jie Ping & Xiang Shu & Tianying Zhao & Fangcheng Yuan & Gang Wang & Yufang Xie & Hang Ci & Hongmo Liu & Yawen Qi & Yongjun Liu & Dan L, 2024. "Integrating muti-omics data to identify tissue-specific DNA methylation biomarkers for cancer risk," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    2. Kyuto Sonehara & Yui Kimura & Yoshiko Nakano & Tatsuya Ozawa & Meiko Takahashi & Ken Suzuki & Takashi Fujii & Yuko Matsushita & Arata Tomiyama & Toshihiro Kishikawa & Kenichi Yamamoto & Tatsuhiko Nait, 2022. "A common deletion at BAK1 reduces enhancer activity and confers risk of intracranial germ cell tumors," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    3. Máire Ní Leathlobhair & Anna Frangou & Ben Kinnersley & Alex J. Cornish & Daniel Chubb & Eszter Lakatos & Prabhu Arumugam & Andreas J. Gruber & Philip Law & Avraam Tapinos & G. Maria Jakobsdottir & Il, 2024. "Genomic landscape of adult testicular germ cell tumours in the 100,000 Genomes Project," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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