Population-based targeted sequencing of 54 candidate genes identifies PALB2 as a susceptibility gene for high-grade serous ovarian cancer

Honglin Song; Ed M Dicks; Jonathan Tyrer; Maria Intermaggio; Georgia Chenevix-Trench; David D Bowtell; Nadia Traficante; James Brenton; Teodora Goranova; Karen Hosking; Anna Piskorz; Elke van Oudenhove; Jen Doherty; Holly R Harris; Mary Anne Rossing; Matthias Duerst; Thilo Dork; Natalia Bogdanova; Francesmary Modugno; Kirsten Moysich; Kunle Odunsi; Roberta Ness; Beth Y Karlan; Jenny Lester; Allan Jensen; Susanne Kruger Kjaer; Estrid Hogdall; Ian G Campbell; Conxi Lazaro; Miguel Angel Pujara; Julie Cunningham; Robert Vierkant; Stacey J Winham; Michelle Hildebrandt; Chad Huff; Donghui Li; Xifeng Wu; Yao Yu; Jennifer B Permuth; Douglas A Levine; Joellen M Schildkraut; Marjorie J Riggan; Andrew Berchuck; Penelope M Webb; Cezary Cybulski; Jacek Gronwald; Anna Jakubowska; Jan Lubinski; Jennifer Alsop; Patricia Harrington; Isaac Chan; Usha Menon; Celeste L Pearce; Anna H Wu; Anna de Fazio; Catherine J Kennedy; Ellen Goode; Susan Ramus; Simon Gayther; Paul Pharoah

Journal article

Population-based targeted sequencing of 54 candidate genes identifies PALB2 as a susceptibility gene for high-grade serous ovarian cancer

Honglin Song, Ed M Dicks, Jonathan Tyrer, Maria Intermaggio, Georgia Chenevix-Trench, David D Bowtell, Nadia Traficante, James Brenton, Teodora Goranova, Karen Hosking, Anna Piskorz, Elke van Oudenhove, Jen Doherty, Holly R Harris, Mary Anne Rossing, Matthias Duerst, Thilo Dork, Natalia Bogdanova, Francesmary Modugno, Kirsten Moysich Show all

JOURNAL OF MEDICAL GENETICS | BMJ PUBLISHING GROUP | Published : 2021

DOI: 10.1136/jmedgenet-2019-106739

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Abstract

PURPOSE: The known epithelial ovarian cancer (EOC) susceptibility genes account for less than 50% of the heritable risk of ovarian cancer suggesting that other susceptibility genes exist. The aim of this study was to evaluate the contribution to ovarian cancer susceptibility of rare deleterious germline variants in a set of candidate genes. METHODS: We sequenced the coding region of 54 candidate genes in 6385 invasive EOC cases and 6115 controls of broad European ancestry. Genes with an increased frequency of putative deleterious variants in cases versus controls were further examined in an independent set of 14 135 EOC cases and 28 655 controls from the Ovarian Cancer Association Consortium..

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University of Melbourne Researchers

Nadia Traficante Author The Sir Peter Maccallum Department of Oncology

David Bowtell Author The Sir Peter Maccallum Department of Oncology

Susan Ramus Author Clinical Pathology

Ian Campbell Author The Sir Peter Maccallum Department of Oncology

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Grants

Awarded by American Cancer Society

Awarded by Cancer Foundation of Western Australia

Awarded by Cancer Institute NSW

Awarded by Cancer Research UK

Awarded by Kraeftens Bekaempelse

Awarded by Medical Research Council

Awarded by U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute

Awarded by U.S. Department of Health and Human Services, National Institutes of Health, National Center for Advancing Translational Sciences

Awarded by National Health and Medical Research Council of Australia

Awarded by U.S. Army Medical Research and Materiel Command

Awarded by U.S Department of Defense Ovarian Cancer Research Program

Funding Acknowledgements

American Cancer Society: SIOP-06-258-01-COUN. Cancer Councils of New South Wales, Victoria, Queensland, South Australia and Tasmania and Cancer Foundation of Western Australia: Multi-State Applications 191, 211 and 182. Cancer Institute NSW: 12/RIG/1-17, 15/RIG/1-16. Cancer Research UK: C490/A10119, C490/A10124, C490/A16561, Cambridge Cancer Centre. Kraeftens Bekaempelse: 94 222 52. Medical Research Council: MR_UU_12023. U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute: K07CA080668, K22 CA193860, MO1RR000056, P50CA159981, R01CA112523, R01CA122443, P30CA15083, P50CA136393, R01CA76016, R01CA126841, R01CA178535, R01CA188943, R01CA61107, R01CA87538, R01CA95023. U.S. Department of Health and Human Services, National Institutes of Health, National Center for Advancing Translational Sciences: UL1TR000124. National Health and Medical Research Council of Australia 199600, 310670, 400281, 400413, 628903, APP1025142. National Institutes of Health Research: Cambridge Biomedical Research Centre, University College London Hospitals Biomedical Research Centre. The Eve Appeal: UKOPS Study. U.S. Army Medical Research and Materiel Command: DAMD17-01-1-0729, DAMD17-02-1-0669, DAMD17-02-1-06. U.S Department of Defense Ovarian Cancer Research Program: W81XWH-07-0449. The University of Cambridge has received salary support in respect of PDPP from the NHS in the East of England through the Clinical Academic Reserve. SG is a recipient of the Barth Family Chair in Cancer Genetics.