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

Autor:	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.; Centre for Cancer Research, The Westmead Institute for Medical Research, Sydney, New South Wales, Australia., Patch AM; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia., Fasching PA; Division of Hematology and Oncology, Department of Medicine, University of California at Los Angeles, David Geffen School of Medicine, Los Angeles, California.; Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany., Beckmann MW; Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany., Lambrechts D; VIB Center for Cancer Biology, VIB, Leuven, Belgium.; Laboratory for Translational Genetics, Department of Human Genetics, University of Leuven, Leuven, Belgium., Vergote I; Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology and Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium., Velez Edwards DR; Department of Obstetrics and Gynecology, Vanderbilt Epidemiology Center, Vanderbilt Genetics Institute, Vanderbilt University School of Medicine, Nashville, Tennessee., Beeghly-Fadiel A; Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee., Benitez J; Human Genetics Group, Spanish National Cancer Centre (CNIO), and Biomedical Network on Rare Diseases (CIBERER), Madrid, Spain., Garcia MJ; Human Genetics Group, Spanish National Cancer Centre (CNIO), and Biomedical Network on Rare Diseases (CIBERER), Madrid, Spain.; Computational Oncology Group, Spanish National Cancer Centre (CNIO), Madrid, Spain., Goodman MT; Cancer Prevention and Control, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.; Department of Biomedical Sciences, Community and Population Health Research Institute, Cedars-Sinai Medical Center, Los Angeles, California., Dörk T; Gynaecology Research Unit, Hannover Medical School, Hannover, Germany., Dürst M; Department of Gynecology, Jena University Hospital - Friedrich Schiller University Jena, Jena, Germany., Modugno F; Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.; Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania.; Womens Cancer Research Center, Magee-Womens Research Institute and Hillman Cancer Center, Pittsburgh, Pennsylvania., Moysich K; Division of Cancer Prevention and Population Sciences, Cancer Pathology & Prevention, Roswell Park Cancer Institute, Buffalo, New York., du Bois A; Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte, Essen, Germany.; Department of Gynecology and Gynecologic Oncology, Dr. Horst Schmidt Kliniken Wiesbaden, Wiesbaden, Germany., Pfisterer J; Gynecologic Oncology Center, Kiel, Germany., Bauman K, Karlan BY; Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California., Lester J; Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California., Cunningham JM; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota., Larson MC; Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota., McCauley BM; Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota., Kjaer SK; Department of Gynecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.; Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark., Jensen A; Department of Lifestyle, Reproduction and Cancer, Danish Cancer Society Research Center, Copenhagen, Denmark., Hogdall CK; Department of Gynecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark., Hogdall E; Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.; Department of Lifestyle, Reproduction and Cancer, Danish Cancer Society Research Center, Copenhagen, Denmark., Schildkraut JM; Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia., Riggan MJ; Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina., Berchuck A; Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina., Cramer DW; Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts., Terry KL; Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.; Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts., Bjorge L; Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.; Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen, Norway., Webb PM, Friedlander M; Prince of Wales Clinical School, University of New South Wales, Sydney, Australia., Pejovic T; Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, Oregon.; Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon., Moffitt M; Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, Oregon.; Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon., Glasspool R; Beatson West of Scotland Cancer Centre and University of Glasgow, Glasgow, United Kingdom., May T; Division of Gynecologic Oncology, Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada., Ene GEV; Division of Gynecologic Oncology, Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada., Huntsman DG; British Columbia's Ovarian Cancer Research (OVCARE) Program, Vancouver General Hospital, BC Cancer Agency and University of British Columbia, British Columbia, Canada.; Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, British Columbia, Canada.; Department of Obstetrics and Gynaecology, The University of British Columbia, Vancouver, British Columbia, Canada.; Department of Molecular Oncology, The University of British Columbia, Vancouver, British Columbia, Canada., Woo M; British Columbia's Ovarian Cancer Research (OVCARE) Program, Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada., Carney ME; Department of Obstetrics and Gynecology, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii., Hinsley S; Cancer Research UK Glasgow Clinical Trials Unit, University of Glasgow, Glasgow, United Kingdom., Heitz F; Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte, Essen, Germany.; Department of Gynecology and Gynecologic Oncology, Dr. Horst Schmidt Kliniken Wiesbaden, Wiesbaden, Germany.; Department for Gynecology with the Center for Oncologic Surgery Charité Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany., Fereday S; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia., Kennedy CJ; Centre for Cancer Research, The Westmead Institute for Medical Research, Sydney, New South Wales, Australia.; Department of Gynaecological Oncology, Westmead Hospital, Sydney, New South Wales, Australia., Edwards SL; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia., Winham SJ; Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota., deFazio A, Pharoah PDP; Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Cambridge, United Kingdom.; Strangeways Research Laboratory, Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Worts Causeway, Cambridge, United Kingdom., Goode EL; Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota., MacGregor S; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia., Chenevix-Trench G; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. georgia.trench@qimrberghofer.edu.au.
Jazyk:	angličtina
Zdroj:	Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology [Cancer Epidemiol Biomarkers Prev] 2021 Sep; Vol. 30 (9), pp. 1669-1680. Date of Electronic Publication: 2021 Jun 23.
DOI:	10.1158/1055-9965.EPI-20-1817
Abstrakt:	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 . (©2021 American Association for Cancer Research.)
Databáze:	MEDLINE
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