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https://repository.monashhealth.org/monashhealthjspui/handle/1/27288| Title: | Mendelian randomization analyses suggest a role for cholesterol in the development of endometrial cancer. | Authors: | Hodgson S.;De Vivo I.;Dennis J.;Dork T.;Dowdy S.C.;Dunning A.M.;Durst M.;Easton D.F.;Ekici A.B.;Fasching P.A.;Fridley B.L.;Friedenreich C.M.;Garcia-Closas M.;Gaudet M.M.;Giles G.G.;Goode E.L.;Gorman M.;Haiman C.A.;Hall P.;Hankinson S.E.;Hein A.;Hillemanns P.;Hoivik E.A.;Holliday E.G.;Hunter D.J.;Kraft P.;Krakstad C.;Lambrechts D.;Le Marchand L.;Liang X.;Lindblom A.;Lissowska J.;Long J.;Lu L.;Magliocco A.M.;Martin L.;McEvoy M.;Milne R.L.;Mints M.;Nassir R.;Otton G.;Palles C.;Pooler L.;Proietto T.;Rebbeck T.R.;Renner S.P.;Risch H.A.;Rubner M.;Runnebaum I.;Sacerdote C.;Sarto G.E.;Schumacher F.;Scott R.J.;Setiawan V.W.;Shah M.;Sheng X.;Shu X.-O.;Southey M.C.;Tham E.;Tomlinson I.;Trovik J.;Turman C.;Tyrer J.P.;Van Den Berg D.;Wang Z.;Wentzensen N.;Xia L.;Xiang Y.-B.;Yang H.P.;Yu H.;Zheng W.;Webb P.M.;Thompson D.J.;Spurdle A.B.;Glubb D.M.;O'Mara T.A.;Chen C. ;Jones A. ;Kho P.-F.;Amant F.;Annibali D.;Ashton K.;Attia J.;Auer P.L.;Beckmann M.W.;Black A.;Brinton L.;Buchanan D.D.;Chanock S.J.;Chen M.M.;Cheng T.H.T.;Cook L.S.;Crous-Bous M.;Czene K. | Institution: | (Kho, Spurdle, Glubb, O'Mara) Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia (Kho) School of Biomedical Science, Queensland University of Technology, Brisbane, QLD, Australia (Amant, Annibali) Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University Hospitals KU Leuven, University of Leuven, Leuven, Belgium (Ashton, Attia, Holliday, Scott) Hunter Medical Research Institute, John Hunter Hospital, Newcastle, NSW, Australia (Ashton) Centre for Information Based Medicine, University of Newcastle, Callaghan, NSW, Australia (Ashton, Scott) Discipline of Medical Genetics, School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle, Callaghan, NSW, Australia (Attia, Holliday, McEvoy) Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Callaghan, NSW, Australia (Auer) Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA, United States (Auer) Zilber School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, WI, United States (Beckmann, Fasching, Hein) Department of Gynecology and Obstetrics, Comprehensive Cancer Center ER-EMN, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany (Black, Brinton, Wang, Wentzensen, Yang) Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, United States (Buchanan, Southey) Department of Clinical Pathology, The University of Melbourne, Melbourne, VIC, Australia (Buchanan, Giles, Milne) Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia (Buchanan) Genomic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, VIC, Australia (Buchanan) University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, VIC, Australia (Chanock, Garcia-Closas) Department of Health and Human Services, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States (Chen) Epidemiology Program, Fred Hutchinson Cancer Research Center, Seattle, WA, United States (Chen, Crous-Bous, De Vivo, Hunter, Kraft, Turman) Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States (Cheng, Gorman, Jones, Palles, Tomlinson) Wellcome Trust Centre for Human Genetics and Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, United Kingdom (Cook) University of New Mexico Health Sciences Center, Albuquerque, NM, United States (Cook, Friedenreich) Department of Cancer Epidemiology and Prevention Research, Alberta Health Services, Calgary, AB, Canada (Crous-Bous, De Vivo, Hankinson) Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States (Czene, Hall) Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (Dennis, Easton, Thompson) Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (Dork, Hillemanns) Gynaecology Research Unit, Hannover Medical School, Hannover, Germany (Dowdy) Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Mayo Clinic, Rochester, MN, United States (Dunning, Easton, Shah, Tyrer) Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, United Kingdom (Durst, Runnebaum) Department of Gynaecology, Jena University Hospital - Friedrich Schiller University, Jena, Germany (Ekici) Institute of Human Genetics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany (Fasching) David Geffen School of Medicine, Department of Medicine Division of Hematology and Oncology, University of California at Los Angeles, Los Angeles, CA, United States (Fridley) Department of Biostatistics, Kansas University Medical Center, Kansas City, KS, United States (Gaudet) Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, GA, United States (Giles, Milne, Southey) Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia (Giles, Milne, Southey) Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia (Goode) Department of Health Science Research, Division of Epidemiology, Mayo Clinic, Rochester, MN, United States (Haiman, Pooler, Setiawan, Sheng, Van Den Berg, Xia) Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States (Hall) Department of Oncology, Sodersjukhuset, Stockholm, Sweden (Hankinson) Department of Biostatistics & Epidemiology, University of Massachusetts, Amherst, Amherst, MA, United States (Hodgson) Department of Clinical Genetics, St George's, University of London, London, United Kingdom (Hoivik, Krakstad, Trovik) Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen, Norway (Hoivik, Krakstad, Trovik) Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway (Hunter, Kraft) Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, MA, United States (Hunter) Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom (Lambrechts) VIB Center for Cancer Biology, Leuven, Belgium (Lambrechts) Laboratory for Translational Genetics, Department of Human Genetics, University of Leuven, Leuven, Belgium (Le Marchand, Yu) Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, United States (Liang) Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, United States (Lindblom, Tham) Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden (Lindblom) Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden (Lissowska) Department of Cancer Epidemiology and Prevention, M. Sklodowska-Curie Cancer Center, Oncology Institute, Warsaw, Poland (Long, Shu, Zheng) Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, United States (Lu, Risch) Chronic Disease Epidemiology, Yale School of Medicine, New Haven, CT, United States (Magliocco) Department of Anatomic Pathology, Moffitt Cancer Center & Research Institute, Tampa, FL, United States (Martin, Tomlinson) Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, United Kingdom (Mints) Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden (Nassir) Department of Biochemistry and Molecular Medicine, University of California Davis, Davis, CA, United States (Otton, Proietto) School of Medicine and Public Health, University of Newcastle, Callaghan, NSW, Australia (Rebbeck) Harvard T.H. Chan School of Public Health, Boston, MA, United States (Rebbeck) Dana-Farber Cancer Institute, Boston, MA, United States (Renner, Rubner) Department of Gynaecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany (Sacerdote) Center for Cancer Prevention (CPO-Peimonte), Turin, Italy (Sacerdote) Human Genetics Foundation (HuGeF), Turin, Italy (Sarto) Department of Obstetrics and Gynecology, School of Medicine and Public Health, University of Wisconsin, Madison, WI, United States (Schumacher) Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, United States (Scott) Division of Molecular Medicine, Pathology North, John Hunter Hospital, Newcastle, NSW, Australia (Tham) Clinical Genetics, Karolinska Institutet, Stockholm, Sweden (Xiang) State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China (Webb) Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia | Issue Date: | 17-Feb-2021 | Copyright year: | 2021 | Publisher: | Wiley-Liss Inc. | Place of publication: | United States | Publication information: | International Journal of Cancer. 148 (2) (pp 307-319), 2021. Date of Publication: 15 Jan 2021. | Journal: | International Journal of Cancer | Abstract: | Blood lipids have been associated with the development of a range of cancers, including breast, lung and colorectal cancer. For endometrial cancer, observational studies have reported inconsistent associations between blood lipids and cancer risk. To reduce biases from unmeasured confounding, we performed a bidirectional, two-sample Mendelian randomization analysis to investigate the relationship between levels of three blood lipids (low-density lipoprotein [LDL] and high-density lipoprotein [HDL] cholesterol, and triglycerides) and endometrial cancer risk. Genetic variants associated with each of these blood lipid levels (P < 5 x 10-8) were identified as instrumental variables, and assessed using genome-wide association study data from the Endometrial Cancer Association Consortium (12 906 cases and 108 979 controls) and the Global Lipids Genetic Consortium (n = 188 578). Mendelian randomization analyses found genetically raised LDL cholesterol levels to be associated with lower risks of endometrial cancer of all histologies combined, and of endometrioid and non-endometrioid subtypes. Conversely, higher genetically predicted HDL cholesterol levels were associated with increased risk of non-endometrioid endometrial cancer. After accounting for the potential confounding role of obesity (as measured by genetic variants associated with body mass index), the association between genetically predicted increased LDL cholesterol levels and lower endometrial cancer risk remained significant, especially for non-endometrioid endometrial cancer. There was no evidence to support a role for triglycerides in endometrial cancer development. Our study supports a role for LDL and HDL cholesterol in the development of non-endometrioid endometrial cancer. Further studies are required to understand the mechanisms underlying these findings.Copyright © 2020 Union for International Cancer Control | DOI: | http://monash.idm.oclc.org/login?url= http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1002/ijc.33206 |
PubMed URL: | 32851660 [http://www.ncbi.nlm.nih.gov/pubmed/?term=32851660] | ISSN: | 0020-7136 | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/27288 | Type: | Article | Subjects: | histopathology high density lipoprotein cholesterol level article body mass genetic variation triacylglycerol/ec [Endogenous Compound] low density lipoprotein cholesterol/ec [Endogenous Compound] high density lipoprotein cholesterol/ec [Endogenous Compound] *cholesterol triacylglycerol blood level single nucleotide polymorphism priority journal prediction *Mendelian randomization analysis major clinical study low density lipoprotein cholesterol level human genome-wide association study cancer classification *cancer risk controlled study disease association disease risk assessment *endometrium cancer/et [Etiology] female gene identification single nucleotide polymorphism human low density lipoprotein cholesterol level major clinical study *Mendelian randomization analysis prediction priority journal triacylglycerol blood level Article body mass cancer classification *cancer risk controlled study disease association disease risk assessment *endometrium cancer / *etiology female gene identification genetic variation genome-wide association study high density lipoprotein cholesterol level histopathology |
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