Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Identification of a Locus Near ULK1 Associated With Progression-Free Survival in Ovarian Cancer

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Genetically Inferred Telomere Length and Testicular Germ Cell Tumor Risk

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Breast cancer risk factors and survival by tumor subtype: Pooled analyses from the breast cancer association consortium

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. A Genetic Risk Score to Personalize Prostate Cancer Screening, Applied to Population Data

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Defining Substantial Lymphovascular Space Invasion in Endometrial Cancer

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Substantial Lymphovascular Space Invasion Is an Adverse Prognostic Factor in High-risk Endometrial Cancer

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Identification of Stably Expressed Reference microRNAs in Epithelial Ovarian Cancer

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Fertility drugs and incidence of thyroid cancer in a Danish nationwide cohort of 146 024 infertile women

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. MCM3 is a novel proliferation marker associated with longer survival for patients with tubo-ovarian high-grade serous carcinoma

    Research output: Contribution to journalJournal articleResearchpeer-review

  • Michael C J Quinn
  • Karen McCue
  • Wei Shi
  • Sharon E Johnatty
  • Jonathan Beesley
  • Andrew Civitarese
  • Tracy A O'Mara
  • Dylan M Glubb
  • Jonathan P Tyrer
  • Sebastian M Armasu
  • Jue-Sheng Ong
  • Puya Gharahkhani
  • Yi Lu
  • Bo Gao
  • Ann-Marie Patch
  • Peter A Fasching
  • Matthias W Beckmann
  • Diether Lambrechts
  • Ignace Vergote
  • Digna R Velez Edwards
  • Alicia Beeghly-Fadiel
  • Javier Benitez
  • Maria J Garcia
  • Marc T Goodman
  • Thilo Dörk
  • Matthias Dürst
  • Francesmary Modugno
  • Kirsten Moysich
  • Andreas du Bois
  • Jacobus Pfisterer
  • Klaus Bauman
  • Beth Y Karlan
  • Jenny Lester
  • Julie M Cunningham
  • Melissa C Larson
  • Bryan M McCauley
  • Susanne K Kjaer
  • Allan Jensen
  • Claus K Hogdall
  • Estrid Hogdall
  • Joellen M Schildkraut
  • Marjorie J Riggan
  • Andrew Berchuck
  • Daniel W Cramer
  • Kathryn L Terry
  • Line Bjorge
  • Penelope M Webb
  • Michael Friedlander
  • Tanja Pejovic
  • Melissa Moffitt
  • AGO Study Group
View graph of relations

BACKGROUND: Many loci have been found to be associated with risk of epithelial ovarian cancer (EOC). However, although there is considerable variation in progression-free survival (PFS), no loci have been found to be associated with outcome at genome-wide levels of significance.

METHODS: We carried out a genome-wide association study (GWAS) of PFS in 2,352 women with EOC who had undergone cytoreductive surgery and standard carboplatin/paclitaxel chemotherapy.

RESULTS: We found seven SNPs at 12q24.33 associated with PFS (P < 5 × 10-8), the top SNP being rs10794418 (HR = 1.24; 95% CI, 1.15-1.34; P = 1.47 × 10-8). High expression of a nearby gene, ULK1, is associated with shorter PFS in EOC, and with poor prognosis in other cancers. SNP rs10794418 is also associated with expression of ULK1 in ovarian tumors, with the allele associated with shorter PFS being associated with higher expression, and chromatin interactions were detected between the ULK1 promoter and associated SNPs in serous and endometrioid EOC cell lines. ULK1 knockout ovarian cancer cell lines showed significantly increased sensitivity to carboplatin in vitro.

CONCLUSIONS: The locus at 12q24.33 represents one of the first genome-wide significant loci for survival for any cancer. ULK1 is a plausible candidate for the target of this association.

IMPACT: This finding provides insight into genetic markers associated with EOC outcome and potential treatment options.See related commentary by Peres and Monteiro, p. 1604.

Original languageEnglish
JournalCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Volume30
Issue number9
Pages (from-to)1669-1680
Number of pages12
ISSN1055-9965
DOIs
Publication statusPublished - Sep 2021

Bibliographical note

©2021 American Association for Cancer Research.

ID: 70956584