Combined Associations of a Polygenic Risk Score and Classical Risk Factors With Breast Cancer Risk,Journal of the National Cancer Institute

当前位置： X-MOL 学术 › J. Natl. Cancer Inst. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Combined Associations of a Polygenic Risk Score and Classical Risk Factors With Breast Cancer Risk
Journal of the National Cancer Institute ( IF 10.3 ) Pub Date : 2020-05-02 , DOI: 10.1093/jnci/djaa056
Pooja Middha Kapoor _{1,

2} , Nasim Mavaddat ₃ , Parichoy Pal Choudhury ₄ , Amber N Wilcox _{4,

5} , Sara Lindström _{6,

7} , Sabine Behrens ₁ , Kyriaki Michailidou _{3,

8} , Joe Dennis ₃ , Manjeet K Bolla ₃ , Qin Wang ₃ , Audrey Jung ₁ , Zomoroda Abu-Ful ₉ , Thomas Ahearn ₄ , Irene L Andrulis _{10,

11} , Hoda Anton-Culver ₁₂ , Volker Arndt ₁₃ , Kristan J Aronson ₁₄ , Paul L Auer _{15,

16} , Laura E Beane Freeman ₄ , Heiko Becher _{17,

18} , Matthias W Beckmann ₁₉ , Alicia Beeghly-Fadiel ₂₀ , Javier Benitez _{21,

22} , Leslie Bernstein ₂₃ , Stig E Bojesen _{24,

25,

26} , Hiltrud Brauch _{24,

25,

26,

27,

28,

29} , Hermann Brenner _{13,

29,

30} , Thomas Brüning ₃₁ , Qiuyin Cai ₂₀ , Daniele Campa _{1,

32} , Federico Canzian ₃₃ , Angel Carracedo _{34,

35} , Brian D Carter ₃₆ , Jose E Castelao ₃₇ , Stephen J Chanock ₄ , Nilanjan Chatterjee _{4,

38,

39} , Georgia Chenevix-Trench ₄₀ , Christine L Clarke ₄₁ , Fergus J Couch ₄₂ , Angela Cox ₄₃ , Simon S Cross ₄₄ , Kamila Czene ₄₅ , James Y Dai ₁₅ , H Shelton Earp ₄₆ , Arif B Ekici ₄₇ , A Heather Eliassen _{48,

49} , Mikael Eriksson ₄₅ , D Gareth Evans _{50,

51} , Peter A Fasching _{19,

52} , Jonine Figueroa _{4,

53,

54} , Lin Fritschi ₅₅ , Marike Gabrielson ₄₅ , Manuela Gago-Dominguez _{34,

56} , Chi Gao _{49,

57} , Susan M Gapstur ₃₆ , Mia M Gaudet ₃₆ , Graham G Giles _{24,

25,

26,

27,

28,

29,

58,

59,

60} , Anna González-Neira ₂₂ , Pascal Guénel ₆₁ , Lothar Haeberle ₆₂ , Christopher A Haiman ₆₃ , Niclas Håkansson ₆₄ , Per Hall _{45,

65} , Ute Hamann ₆₆ , Sigrid Hatse ₆₇ , Jane Heyworth ₆₈ , Bernd Holleczek ₆₉ , Robert N Hoover ₄ , John L Hopper ₅₉ , Anthony Howell ₇₀ , David J Hunter _{49,

57,

71} , , , Esther M John ₇₂ , Michael E Jones ₇₃ , Rudolf Kaaks ₁ , Renske Keeman ₇₄ , Cari M Kitahara ₇₅ , Yon-Dschun Ko ₇₆ , Stella Koutros ₄ , Allison W Kurian ₇₂ , Diether Lambrechts _{77,

78} , Loic Le Marchand ₇₉ , Eunjung Lee ₆₃ , Flavio Lejbkowicz ₉ , Martha Linet ₇₅ , Jolanta Lissowska ₈₀ , Ana Llaneza ₈₁ , Robert J MacInnis _{58,

59} , Maria Elena Martinez _{56,

82} , Tabea Maurer ₈₃ , Catriona McLean ₈₄ , Susan L Neuhausen ₂₃ , William G Newman _{50,

51} , Aaron Norman ₈₅ , Katie M O'Brien ₈₆ , Andrew F Olshan ₈₇ , Janet E Olson ₈₅ , Håkan Olsson ₈₈ , Nick Orr ₈₉ , Charles M Perou ₉₀ , Guillermo Pita ₉₁ , Eric C Polley ₈₅ , Ross L Prentice ₁₅ , Gad Rennert ₉ , Hedy S Rennert ₉ , Kathryn J Ruddy ₉₂ , Dale P Sandler ₈₆ , Christobel Saunders ₉₃ , Minouk J Schoemaker ₇₃ , Ben Schöttker _{13,

94} , Fredrick Schumacher ₉₅ , Christopher Scott ₈₅ , Rodney J Scott _{24,

25,

26,

27,

28,

29,

58,

59,

60,

96,

97,

98} , Xiao-Ou Shu ₂₀ , Ann Smeets ₉₉ , Melissa C Southey _{60,

100,

101} , John J Spinelli _{102,

103} , Jennifer Stone _{59,

104} , Anthony J Swerdlow _{73,

105} , Rulla M Tamimi _{48,

49,

57} , Jack A Taylor _{86,

106} , Melissa A Troester ₈₇ , Celine M Vachon ₁₀₇ , Elke M van Veen _{50,

51} , Xiaoliang Wang _{6,

7} , Clarice R Weinberg ₁₀₈ , Caroline Weltens ₁₀₉ , Walter Willett _{49,

110,

111} , Stacey J Winham ₁₁₂ , Alicja Wolk _{64,

113} , Xiaohong R Yang ₄ , Wei Zheng ₂₀ , Argyrios Ziogas ₁₂ , Alison M Dunning ₁₁₄ , Paul D P Pharoah _{3,

114} , Marjanka K Schmidt _{74,

115} , Peter Kraft _{49,

57} , Douglas F Easton _{3,

114} , Roger L Milne _{24,

25,

26,

27,

28,

29,

58,

59,

60,

96,

97,

98} , Montserrat García-Closas ₄ , Jenny Chang-Claude _{1,

83}

Affiliation

Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Faculty of Medicine, University of Heidelberg, Heidelberg, Germany.
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Department of Epidemiology, University of Washington School of Public Health, Seattle, WA, USA.
Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Biostatistics Unit and the Cyprus, School of Molecular Medicine, Cyprus Institute of Neurology & Genetics, Nicosia, Cyprus.
Clalit National Cancer Control Center, Carmel Medical Center and Technion Faculty of Medicine, Haifa, Israel.
Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON, Canada.
Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
Department of Epidemiology, Genetic Epidemiology Research Institute, University of California Irvine, Irvine, CA, USA.
Division of Clinical Epidemiology and Aging Research, C070, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Department of Public Health Sciences and Cancer Research Institute, Queen's University, Kingston, ON, Canada.
Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Zilber School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, WI, USA.
Institute of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Institute of Biometry and Clinical Epidemiology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Department of Gynecology and Obstetrics, Comprehensive Cancer Center ER-EMN, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
Centro de Investigación en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA.
Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.
iFIT-Cluster of Excellence, University of Tuebingen, Tuebingen, Germany.
German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.
Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, Germany.
Department of Biology, University of Pisa, Pisa, Italy.
Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Genomic Medicine Group, Galician Foundation of Genomic Medicine, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago, SERGAS, Santiago de Compostela, Spain.
Centro de Investigación en Red de Enfermedades Raras (CIBERER) y Centro Nacional de Genotipado (CEGEN-PRB2), Universidad de Santiago de Compostela, Santiago De Compostela, Spain.
Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, GA, USA.
Oncology and Genetics Unit, Instituto de Investigacion Sanitaria Galicia Sur (IISGS), Xerencia de Xestion Integrada de Vigo-SERGAS, Vigo, Spain.
Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Department of Oncology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Westmead Institute for Medical Research, University of Sydney, Sydney, New South Wales, Australia.
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Sheffield Institute for Nucleic Acids (SInFoNiA), Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK.
Academic Unit of Pathology, Department of Neuroscience, University of Sheffield, Sheffield, UK.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Institute of Human Genetics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany.
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
North West Genomics Laboratory Hub, Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
David Geffen School of Medicine, Department of Medicine Division of Hematology and Oncology, University of California at Los Angeles, Los Angeles, CA, USA.
Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, UK.
Cancer Research UK Edinburgh Centre, Edinburgh, UK.
School of Public Health, Curtin University, Perth, Western Australia, Australia.
Moores Cancer Center, University of California San Diego, La Jolla, CA, USA.
Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.
Cancer & Environment Group, Center for Research in Epidemiology and Population Health (CESP), INSERM, University Paris-Sud, University Paris-Saclay, Villejuif, France.
Department of Gynaecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany.
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Department of Oncology, Södersjukhuset, Stockholm, Sweden.
Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Laboratory of Experimental Oncology (LEO), Department of Oncology, Leuven Cancer Institute, KU Leuven, Leuven, Belgium.
School of Population and Global Health, The University of Western Australia, Perth, Western Australia, Australia.
Saarland Cancer Registry, Saarbrücken, Germany.
Division of Cancer Sciences, University of Manchester, Manchester, UK.
Nuffield Department of Population Health, University of Oxford, Oxford, UK.
Division of Oncology, Departments of Epidemiology & Population Health and of Medicine, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
Division of Molecular Pathology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany.
VIB Center for Cancer Biology, VIB, Leuven, Belgium.
Laboratory for Translational Genetics, Department of Human Genetics, University of Leuven, Leuven, Belgium.
Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
Department of Cancer Epidemiology and Prevention, M. Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
General and Gastroenterology Surgery Service, Hospital Universitario Central de Asturias, Oviedo, Spain.
Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA, USA.
Cancer Epidemiology Group, University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Anatomical Pathology, The Alfred Hospital, Melbourne, Victoria, Australia.
Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA.
Department of Epidemiology, Gillings School of Global Public Health and UNC Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Department of Cancer Epidemiology, Clinical Sciences, Lund University, Lund, Sweden.
Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, Ireland, UK.
Department of Genetics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Human Genotyping-CEGEN Unit, Human Cancer Genetic Program, Spanish National Cancer Research Centre, Madrid, Spain.
Department of Oncology, Mayo Clinic, Rochester, MN, USA.
School of Medicine, University of Western Australia, Perth, Western Australia, Australia.
Network Aging Research, University of Heidelberg, Heidelberg, Germany.
Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA.
Division of Molecular Medicine, Pathology North, 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.
Hunter Medical Research Institute, John Hunter Hospital, Newcastle, New South Wales, Australia.
Department of Surgical Oncology, University Hospitals Leuven, Leuven, Belgium.
Department of Clinical Pathology, The University of Melbourne, Melbourne, Victoria, Australia.
Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia.
Population Oncology, BC Cancer, Vancouver, BC, Canada.
School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada.
The Curtin UWA Centre for Genetic Origins of Health and Disease, Curtin University and University of Western Australia, Perth, Western Australia, Australia.
Division of Breast Cancer Research, The Institute of Cancer Research, London, UK.
Epigenetic and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA.
Department of Health Science Research, Division of Epidemiology, Mayo Clinic, Rochester, MN, USA.
Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA.
Leuven Multidisciplinary Breast Center, Department of Oncology, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium.
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Division of Biomedical Statistics and Informatics, Department of Health Science Research, Mayo Clinic, Rochester, MN, USA.
Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
Division of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.

We evaluated the joint associations between a new 313-variant PRS (PRS₃₁₃) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS₃₁₃ odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS₃₁₃ and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS₃₁₃ and family history) and, on average, 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer.

中文翻译：

多基因风险评分和经典风险因素与乳腺癌风险的联合关联

我们评估了新的 313 变体 PRS (PRS ₃₁₃ ) 与欧洲血统女性基于问卷调查的乳腺癌风险因素之间的联合关联，使用来自乳腺癌协会联盟的 72 284 例病例和 80 354 例对照。使用标准逻辑回归和新开发的针对乳腺癌总体风险和雌激素受体状态的仅病例方法评估相互作用。在考虑了多次测试后，我们没有发现证据表明每个标准差的 PRS ₃₁₃比值比在由个体风险因素定义的各层之间存在差异。_{拟合优度检验并未拒绝 PRS 313}之间的乘法模型假设和每个风险因素。_{对于具有较高遗传风险（PRS 313}和家族史）的女性，与经典风险因素相关的乳腺癌预计绝对终生风险的变化更大，平均而言，最高和最低遗传风险十分位数高 17.5%。这些发现对于乳腺癌风险增加的女性的风险预防具有重要意义。

更新日期：2020-05-02

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文

全部期刊列表>>