Association of polygenic risk score with the risk of chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis

Author:

Kleinstern Geffen1ORCID,Camp Nicola J.2,Goldin Lynn R.3,Vachon Celine M.1,Vajdic Claire M.4,de Sanjose Silvia56,Weinberg J. Brice789,Benavente Yolanda56,Casabonne Delphine56,Liebow Mark10,Nieters Alexandra11,Hjalgrim Henrik1213,Melbye Mads1214,Glimelius Bengt15,Adami Hans-Olov16,Boffetta Paolo17,Brennan Paul18,Maynadie Marc19,McKay James18,Cocco Pier Luigi20,Shanafelt Tait D.21,Call Timothy G.21,Norman Aaron D.1,Hanson Curtis22,Robinson Dennis1,Chaffee Kari G.1,Brooks-Wilson Angela R.2324,Monnereau Alain252627,Clavel Jacqueline2627,Glenn Martha2,Curtin Karen2,Conde Lucia28,Bracci Paige M.29,Morton Lindsay M.3,Cozen Wendy3031,Severson Richard K.32,Chanock Stephen J.3,Spinelli John J.3334,Johnston James B.35,Rothman Nathaniel3,Skibola Christine F.36,Leis Jose F.37,Kay Neil E.20,Smedby Karin E.38,Berndt Sonja I.3,Cerhan James R.1,Caporaso Neil3,Slager Susan L.1

Affiliation:

1. Department of Health Sciences Research, Mayo Clinic, Rochester, MN;

2. Huntsman Cancer Institute and Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT;

3. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD;

4. Centre for Big Data Research in Health, University of New South Wales, Sydney, NSW, Australia;

5. CIBER de Epidemiología y Salud Pública, Barcelona, Spain;

6. Cancer Epidemiology Research Programme, Catalan Institute of Oncology, Institute d’Investigacio Biomedica de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain;

7. Department of Medicine and

8. Department of Immunology, Duke University Medical Center, Durham, NC;

9. Durham Veterans Affairs Medical Center, Durham, NC;

10. Division of General Internal Medicine, Mayo Clinic, Rochester, MN;

11. Center for Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg, Baden-Württemberg, Germany;

12. Department of Epidemiology Research, Division of Health Surveillance and Research, Statens Serum Institut, Copenhagen, Denmark;

13. Department of Hematology, Rigshospitalet, Copenhagen, Denmark;

14. Department of Medicine, Stanford University School of Medicine, Stanford, CA;

15. Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden;

16. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden;

17. The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY;

18. International Agency for Research on Cancer, Lyon, France;

19. Registre des Hémopathies Malignes de Côte d'Or, INSERM UMR1231, Université de Bourgogne-Franche-Comté, Dijon, France;

20. Department of Medical Sciences and Public Health, Occupational Health Section, University of Cagliari, Monserrato, Italy;

21. Division of Hematology and

22. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN;

23. Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada;

24. Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC, Canada;

25. Registre des Hémopathies Malignes de la Gironde, Institut Bergonié, University of Bordeaux, INSERM, Team EPICENE, UMR 1219, Bordeaux, France;

26. Epidemiology of Childhood and Adolescent Cancers Group, INSERM, Center of Research in Epidemiology and Statistics Sorbonne Paris Cité, Paris, France;

27. Université Paris Descartes, Paris, France;

28. UCL Cancer Institute, London, United Kingdom;

29. Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA;

30. Department of Preventive Medicine and

31. Norris Comprehensive Cancer Center, USC Keck School of Medicine, University of Southern California, Los Angeles, CA;

32. Department of Family Medicine and Public Health Sciences, Wayne State University, Detroit, MI;

33. Cancer Control Research, BC Cancer Agency, Vancouver, BC, Canada;

34. School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada;

35. Department of Medical Oncology, Cancer Care Manitoba, Winnipeg, MB, Canada;

36. Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA;

37. Department of Hematology and Oncology, Mayo Clinic, Phoenix, AZ; and

38. Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden

Abstract

Key Points PRS, based on the known CLL loci, predicts CLL risk with high discrimination. This PRS predicts risk of monoclonal B-cell lymphocytosis, a precursor to CLL and a condition that has clinical impact beyond risk for CLL.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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