Article open access publication

Genetic variation in the ADIPOQ gene, adiponectin concentrations and risk of colorectal cancer: a Mendelian Randomization analysis using data from three large cohort studies

European Journal of Epidemiology, Springer Nature, ISSN 1573-7284

Volume 32, 5, 2017

DOI:10.1007/s10654-017-0262-y, Dimensions: pub.1085596763, PMC: PMC5535815, PMID: 28550647,



  1. (1) Harvard University, grid.38142.3c
  2. (2) Max Delbrück Center for Molecular Medicine, grid.419491.0
  3. (3) Massachusetts General Hospital, grid.32224.35
  4. (4) German Institute of Human Nutrition, grid.418213.d
  5. (5) Hellenic Health Foundation, grid.424637.0
  6. (6) University College London, grid.83440.3b
  7. (7) International Agency For Research On Cancer, grid.17703.32
  8. (8) University of Ioannina, grid.9594.1
  9. (9) Imperial College London, grid.7445.2
  10. (10) Cancer Registry of Norway, grid.418941.1
  11. (11) Folkhälsans Forskningscentrum, grid.428673.c
  12. (12) Karolinska Institute, grid.4714.6
  13. (13) The Arctic University of Norway, grid.10919.30
  14. (14) National Institute for Public Health and the Environment, grid.31147.30
  15. (15) University of Malaya, grid.10347.31
  16. (16) National Cancer Centre Singapore, grid.410724.4
  17. (17) Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA
  18. (18) Odense University Hospital, grid.7143.1, Southern Denmark Region
  19. (19) University of Southern Denmark, grid.10825.3e, SDU
  20. (20) Aarhus University, grid.7048.b, AU
  21. (21) German Cancer Research Center, grid.7497.d
  22. (22) Lund University, grid.4514.4
  23. (23) University Medical Center Utrecht, grid.7692.a
  24. (24) Fondazione IRCCS Istituto Nazionale dei Tumori, grid.417893.0
  25. (25) University of Naples Federico II, grid.4691.a
  26. (26) Umeå University, grid.12650.30
  27. (27) Instituto Murciano de Investigación Biosanitaria, grid.452553.0
  28. (28) Institute of Health Carlos III, grid.413448.e
  29. (29) Andalusian School of Public Health, grid.413740.5
  30. (30) Public Health Directorate, Asturias, Spain
  31. (31) Public Health Direction and Biodonostia Research Institute- Ciberesp, Basque Regional Health Department, San Sebastian, Spain
  32. (32) Danish Cancer Society, grid.417390.8
  33. (33) University of Oxford, grid.4991.5
  34. (34) Centre for research in epidemiology and population health, grid.463845.8
  35. (35) Institut Gustave Roussy, grid.14925.3b
  36. (36) Department of Gastroenterology, Assistance Publique-Hôpitaux de Paris (AP-HP), University hospitals Paris-Sud, Site de Bicêtre, Paris Sud University, Paris XI, Le Kremlin Bicêtre, Villejuif, France
  37. (37) Cancer Council Victoria, grid.3263.4
  38. (38) Human Genetics Foundation, grid.428948.b
  39. (39) University of Melbourne, grid.1008.9
  40. (40) Catalan Institute of Oncology, grid.418701.b
  41. (41) Istituto per lo Studio e la Prevenzione Oncologica, grid.417623.5
  42. (42) Division of MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA
  43. (43) Dana-Farber Cancer Institute, grid.65499.37
  44. (44) Broad Institute, grid.66859.34
  45. (45) Charité, grid.6363.0


Higher levels of circulating adiponectin have been related to lower risk of colorectal cancer in several prospective cohort studies, but it remains unclear whether this association may be causal. We aimed to improve causal inference in a Mendelian Randomization meta-analysis using nested case-control studies of the European Prospective Investigation into Cancer and Nutrition (EPIC, 623 cases, 623 matched controls), the Health Professionals Follow-up Study (HPFS, 231 cases, 230 controls) and the Nurses' Health Study (NHS, 399 cases, 774 controls) with available data on pre-diagnostic adiponectin concentrations and selected single nucleotide polymorphisms in the ADIPOQ gene. We created an ADIPOQ allele score that explained approximately 3% of the interindividual variation in adiponectin concentrations. The ADIPOQ allele score was not associated with risk of colorectal cancer in logistic regression analyses (pooled OR per score-unit unit 0.97, 95% CI 0.91, 1.04). Genetically determined twofold higher adiponectin was not significantly associated with risk of colorectal cancer using the ADIPOQ allele score as instrumental variable (pooled OR 0.73, 95% CI 0.40, 1.34). In a summary instrumental variable analysis (based on previously published data) with higher statistical power, no association between genetically determined twofold higher adiponectin and risk of colorectal cancer was observed (0.99, 95% CI 0.93, 1.06 in women and 0.94, 95% CI 0.88, 1.01 in men). Thus, our study does not support a causal effect of circulating adiponectin on colorectal cancer risk. Due to the limited genetic determination of adiponectin, larger Mendelian Randomization studies are necessary to clarify whether adiponectin is causally related to lower risk of colorectal cancer.


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