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Identification of a Locus Near ULK1 Associated With Progression-Free Survival in Ovarian Cancer.
Quinn, Michael C J; McCue, Karen; Shi, Wei; Johnatty, Sharon E; Beesley, Jonathan; Civitarese, Andrew; O'Mara, Tracy A; Glubb, Dylan M; Tyrer, Jonathan P; Armasu, Sebastian M; Ong, Jue-Sheng; Gharahkhani, Puya; Lu, Yi; Gao, Bo; Patch, Ann-Marie; Fasching, Peter A; Beckmann, Matthias W; Lambrechts, Diether; Vergote, Ignace; Velez Edwards, Digna R; Beeghly-Fadiel, Alicia; Benitez, Javier; Garcia, Maria J; Goodman, Marc T; Dörk, Thilo; Dürst, Matthias; Modugno, Francesmary; Moysich, Kirsten; du Bois, Andreas; Pfisterer, Jacobus; Bauman, Klaus; Karlan, Beth Y; Lester, Jenny; Cunningham, Julie M; Larson, Melissa C; McCauley, Bryan M; Kjaer, Susanne K; Jensen, Allan; Hogdall, Claus K; Hogdall, Estrid; Schildkraut, Joellen M; Riggan, Marjorie J; Berchuck, Andrew; Cramer, Daniel W; Terry, Kathryn L; Bjorge, Line; Webb, Penelope M; Friedlander, Michael; Pejovic, Tanja; Moffitt, Melissa.
Afiliación
  • Quinn MCJ; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
  • McCue K; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
  • Shi W; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
  • Johnatty SE; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
  • Beesley J; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
  • Civitarese A; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
  • O'Mara TA; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
  • Glubb DM; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
  • Tyrer JP; Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Cambridge, United Kingdom.
  • Armasu SM; Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota.
  • Ong JS; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
  • Gharahkhani P; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
  • Lu Y; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
  • Gao B; Crown Princess Mary Cancer Care Centre, Westmead Hospital, Sydney, New South Wales, Australia.
  • Patch AM; Centre for Cancer Research, The Westmead Institute for Medical Research, Sydney, New South Wales, Australia.
  • Fasching PA; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
  • Beckmann MW; Division of Hematology and Oncology, Department of Medicine, University of California at Los Angeles, David Geffen School of Medicine, Los Angeles, California.
  • Lambrechts D; Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany.
  • Vergote I; Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany.
  • Velez Edwards DR; VIB Center for Cancer Biology, VIB, Leuven, Belgium.
  • Beeghly-Fadiel A; Laboratory for Translational Genetics, Department of Human Genetics, University of Leuven, Leuven, Belgium.
  • Benitez J; Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology and Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium.
  • Garcia MJ; Department of Obstetrics and Gynecology, Vanderbilt Epidemiology Center, Vanderbilt Genetics Institute, Vanderbilt University School of Medicine, Nashville, Tennessee.
  • Goodman MT; Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee.
  • Dörk T; Human Genetics Group, Spanish National Cancer Centre (CNIO), and Biomedical Network on Rare Diseases (CIBERER), Madrid, Spain.
  • Dürst M; Human Genetics Group, Spanish National Cancer Centre (CNIO), and Biomedical Network on Rare Diseases (CIBERER), Madrid, Spain.
  • Modugno F; Computational Oncology Group, Spanish National Cancer Centre (CNIO), Madrid, Spain.
  • Moysich K; Cancer Prevention and Control, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.
  • du Bois A; Department of Biomedical Sciences, Community and Population Health Research Institute, Cedars-Sinai Medical Center, Los Angeles, California.
  • Pfisterer J; Gynaecology Research Unit, Hannover Medical School, Hannover, Germany.
  • Bauman K; Department of Gynecology, Jena University Hospital - Friedrich Schiller University Jena, Jena, Germany.
  • Karlan BY; Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
  • Lester J; Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania.
  • Cunningham JM; Womens Cancer Research Center, Magee-Womens Research Institute and Hillman Cancer Center, Pittsburgh, Pennsylvania.
  • Larson MC; Division of Cancer Prevention and Population Sciences, Cancer Pathology & Prevention, Roswell Park Cancer Institute, Buffalo, New York.
  • McCauley BM; Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte, Essen, Germany.
  • Kjaer SK; Department of Gynecology and Gynecologic Oncology, Dr. Horst Schmidt Kliniken Wiesbaden, Wiesbaden, Germany.
  • Jensen A; Gynecologic Oncology Center, Kiel, Germany.
  • Hogdall E; Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California.
  • Schildkraut JM; Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California.
  • Riggan MJ; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
  • Berchuck A; Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota.
  • Cramer DW; Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota.
  • Terry KL; Department of Gynecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
  • Bjorge L; Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.
  • Webb PM; Department of Lifestyle, Reproduction and Cancer, Danish Cancer Society Research Center, Copenhagen, Denmark.
  • Friedlander M; Department of Gynecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
  • Pejovic T; Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.
  • Moffitt M; Department of Lifestyle, Reproduction and Cancer, Danish Cancer Society Research Center, Copenhagen, Denmark.
Cancer Epidemiol Biomarkers Prev ; 30(9): 1669-1680, 2021 09.
Article en En | MEDLINE | ID: mdl-34162658
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.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Péptidos y Proteínas de Señalización Intracelular / Homólogo de la Proteína 1 Relacionada con la Autofagia / Carcinoma Epitelial de Ovario Tipo de estudio: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Límite: Female / Humans Idioma: En Revista: Cancer Epidemiol Biomarkers Prev Asunto de la revista: BIOQUIMICA / EPIDEMIOLOGIA / NEOPLASIAS Año: 2021 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Péptidos y Proteínas de Señalización Intracelular / Homólogo de la Proteína 1 Relacionada con la Autofagia / Carcinoma Epitelial de Ovario Tipo de estudio: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Límite: Female / Humans Idioma: En Revista: Cancer Epidemiol Biomarkers Prev Asunto de la revista: BIOQUIMICA / EPIDEMIOLOGIA / NEOPLASIAS Año: 2021 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos