Mendelian randomization analyses suggest a role for cholesterol in the development of endometrial cancer.

Autor: Kho PF; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.; School of Biomedical Science, Queensland University of Technology, Brisbane, Queensland, Australia., Amant F; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University Hospitals KU Leuven, University of Leuven, Leuven, Belgium., Annibali D; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University Hospitals KU Leuven, University of Leuven, Leuven, Belgium., Ashton K; Hunter Medical Research Institute, John Hunter Hospital, Newcastle, New South Wales, Australia.; Centre for Information Based Medicine, University of Newcastle, Callaghan, New South Wales, Australia.; Discipline of Medical Genetics, School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle, Callaghan, New South Wales, Australia., Attia J; Hunter Medical Research Institute, John Hunter Hospital, Newcastle, New South Wales, Australia.; Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia., Auer PL; Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.; Zilber School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA., Beckmann MW; Department of Gynecology and Obstetrics, Comprehensive Cancer Center ER-EMN, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany., Black A; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA., Brinton L; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA., Buchanan DD; Department of Clinical Pathology, The University of Melbourne, Melbourne, Victoria, Australia.; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.; Genomic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Victoria, Australia.; University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, Victoria, Australia., Chanock SJ; Department of Health and Human Services, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA., Chen C; Epidemiology Program, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA., Chen MM; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA., Cheng THT; Wellcome Trust Centre for Human Genetics and Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, UK., Cook LS; University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA.; Department of Cancer Epidemiology and Prevention Research, Alberta Health Services, Calgary, Alberta, Canada., Crous-Bous M; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA., Czene K; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden., De Vivo I; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA., Dennis J; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK., Dörk T; Gynaecology Research Unit, Hannover Medical School, Hannover, Germany., Dowdy SC; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Mayo Clinic, Rochester, Minnesota, USA., Dunning AM; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK., Dürst M; Department of Gynaecology, Jena University Hospital - Friedrich Schiller University, Jena, Germany., Easton DF; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK., Ekici AB; Institute of Human Genetics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany., Fasching PA; Department of Gynecology and Obstetrics, Comprehensive Cancer Center ER-EMN, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.; David Geffen School of Medicine, Department of Medicine Division of Hematology and Oncology, University of California at Los Angeles, Los Angeles, California, USA., Fridley BL; Department of Biostatistics, Kansas University Medical Center, Kansas City, Kansas, USA., Friedenreich CM; Department of Cancer Epidemiology and Prevention Research, Alberta Health Services, Calgary, Alberta, Canada., García-Closas M; Department of Health and Human Services, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA., Gaudet MM; Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia, USA., Giles GG; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.; Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.; Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia., Goode EL; Department of Health Science Research, Division of Epidemiology, Mayo Clinic, Rochester, Minnesota, USA., Gorman M; Wellcome Trust Centre for Human Genetics and Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, UK., Haiman CA; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA., Hall P; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.; Department of Oncology, Södersjukhuset, Stockholm, Sweden., Hankinson SE; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.; Department of Biostatistics & Epidemiology, University of Massachusetts, Amherst, Amherst, Massachusetts, USA., Hein A; Department of Gynecology and Obstetrics, Comprehensive Cancer Center ER-EMN, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany., Hillemanns P; Gynaecology Research Unit, Hannover Medical School, Hannover, Germany., Hodgson S; Department of Clinical Genetics, St George's, University of London, London, UK., Hoivik EA; Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen, Norway.; Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway., Holliday EG; Hunter Medical Research Institute, John Hunter Hospital, Newcastle, New South Wales, Australia.; Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia., Hunter DJ; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.; Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.; Nuffield Department of Population Health, University of Oxford, Oxford, UK., Jones A; Wellcome Trust Centre for Human Genetics and Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, UK., Kraft P; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.; Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA., Krakstad C; Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen, Norway.; Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway., Lambrechts D; VIB Center for Cancer Biology, Leuven, Belgium.; Laboratory for Translational Genetics, Department of Human Genetics, University of Leuven, Leuven, Belgium., Le Marchand L; Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, USA., Liang X; Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA., Lindblom A; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.; Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden., Lissowska J; Department of Cancer Epidemiology and Prevention, M. Sklodowska-Curie Cancer Center, Oncology Institute, Warsaw, Poland., Long J; Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA., Lu L; Chronic Disease Epidemiology, Yale School of Medicine, New Haven, Connecticut, USA., Magliocco AM; Department of Anatomic Pathology, Moffitt Cancer Center & Research Institute, Tampa, Florida, USA., Martin L; Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK., McEvoy M; Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia., Milne RL; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.; Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.; Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia., Mints M; Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden., Nassir R; Department of Biochemistry and Molecular Medicine, University of California Davis, Davis, California, USA., Otton G; School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia., Palles C; Wellcome Trust Centre for Human Genetics and Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, UK., Pooler L; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA., Proietto T; School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia., Rebbeck TR; Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.; Dana-Farber Cancer Institute, Boston, Massachusetts, USA., Renner SP; Department of Gynaecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany., Risch HA; Chronic Disease Epidemiology, Yale School of Medicine, New Haven, Connecticut, USA., Rübner M; Department of Gynaecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany., Runnebaum I; Department of Gynaecology, Jena University Hospital - Friedrich Schiller University, Jena, Germany., Sacerdote C; Center for Cancer Prevention (CPO-Peimonte), Turin, Italy.; Human Genetics Foundation (HuGeF), Turin, Italy., Sarto GE; Department of Obstetrics and Gynecology, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA., Schumacher F; Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio, USA., Scott RJ; Hunter Medical Research Institute, John Hunter Hospital, Newcastle, New South Wales, Australia.; Discipline of Medical Genetics, School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle, Callaghan, New South Wales, Australia.; Division of Molecular Medicine, Pathology North, John Hunter Hospital, Newcastle, New South Wales, Australia., Setiawan VW; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA., Shah M; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK., Sheng X; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA., Shu XO; Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA., Southey MC; Department of Clinical Pathology, The University of Melbourne, Melbourne, Victoria, Australia.; Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.; Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia., Tham E; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.; Clinical Genetics, Karolinska Institutet, Stockholm, Sweden., Tomlinson I; Wellcome Trust Centre for Human Genetics and Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, UK.; Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK., Trovik J; Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen, Norway.; Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway., Turman C; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA., Tyrer JP; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK., Van Den Berg D; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA., Wang Z; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA., Wentzensen N; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA., Xia L; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA., Xiang YB; State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China., Yang HP; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA., Yu H; Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, USA., Zheng W; Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA., Webb PM; Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia., Thompson DJ; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK., Spurdle AB; 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., O'Mara TA; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Jazyk: angličtina
Zdroj: International journal of cancer [Int J Cancer] 2021 Jan 15; Vol. 148 (2), pp. 307-319. Date of Electronic Publication: 2020 Aug 07.
DOI: 10.1002/ijc.33206
Abstrakt: 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 × 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.
(© 2020 Union for International Cancer Control.)
Databáze: MEDLINE
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