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Tang H, Jiang L, Stolzenberg-Solomon RZ, et al. Genome-Wide Gene-Diabetes and Gene-Obesity Interaction Scan in 8,255 Cases and 11,900 Controls from PanScan and PanC4 Consortia. Cancer Epidemiol Biomarkers Prev. 2020;29(9):1784-1791doi: 10.1158/1055-9965.EPI-20-0275.
Tang, H., Jiang, L., Stolzenberg-Solomon, R. Z., Arslan, A. A., Beane Freeman, L. E., Bracci, P. M., Brennan, P., Canzian, F., Du, M., Gallinger, S., Giles, G. G., Goodman, P. J., Kooperberg, C., Le Marchand, L., Neale, R. E., Shu, X. O., Visvanathan, K., White, E., Zheng, W., Albanes, D., Andreotti, G., Babic, A., Bamlet, W. R., Berndt, S. I., Blackford, A., Bueno-de-Mesquita, B., Buring, J. E., Campa, D., Chanock, S. J., Childs, E., Duell, E. J., Fuchs, C., Gaziano, J. M., Goggins, M., Hartge, P., Hassam, M. H., Holly, E. A., Hoover, R. N., Hung, R. J., Kurtz, R. C., Lee, I. M., Malats, N., Milne, R. L., Ng, K., Oberg, A. L., Orlow, I., Peters, U., Porta, M., Rabe, K. G., Rothman, N., Scelo, G., Sesso, H. D., Silverman, D. T., Thompson, I. M., Tjønneland, A., Trichopoulou, A., Wactawski-Wende, J., Wentzensen, N., Wilkens, L. R., Yu, H., Zeleniuch-Jacquotte, A., Amundadottir, L. T., Jacobs, E. J., Petersen, G. M., Wolpin, B. M., Risch, H. A., Chatterjee, N., Klein, A. P., Li, D., Kraft, P., & Wei, P. (2020). Genome-Wide Gene-Diabetes and Gene-Obesity Interaction Scan in 8,255 Cases and 11,900 Controls from PanScan and PanC4 Consortia. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 29(9), 1784-1791. https://doi.org/10.1158/1055-9965.EPI-20-0275
Tang, Hongwei, et al. "Genome-Wide Gene-Diabetes and Gene-Obesity Interaction Scan in 8,255 Cases and 11,900 Controls from PanScan and PanC4 Consortia." Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology vol. 29,9 (2020): 1784-1791. doi: https://doi.org/10.1158/1055-9965.EPI-20-0275
Tang H, Jiang L, Stolzenberg-Solomon RZ, Arslan AA, Beane Freeman LE, Bracci PM, Brennan P, Canzian F, Du M, Gallinger S, Giles GG, Goodman PJ, Kooperberg C, Le Marchand L, Neale RE, Shu XO, Visvanathan K, White E, Zheng W, Albanes D, Andreotti G, Babic A, Bamlet WR, Berndt SI, Blackford A, Bueno-de-Mesquita B, Buring JE, Campa D, Chanock SJ, Childs E, Duell EJ, Fuchs C, Gaziano JM, Goggins M, Hartge P, Hassam MH, Holly EA, Hoover RN, Hung RJ, Kurtz RC, Lee IM, Malats N, Milne RL, Ng K, Oberg AL, Orlow I, Peters U, Porta M, Rabe KG, Rothman N, Scelo G, Sesso HD, Silverman DT, Thompson IM, Tjønneland A, Trichopoulou A, Wactawski-Wende J, Wentzensen N, Wilkens LR, Yu H, Zeleniuch-Jacquotte A, Amundadottir LT, Jacobs EJ, Petersen GM, Wolpin BM, Risch HA, Chatterjee N, Klein AP, Li D, Kraft P, Wei P. Genome-Wide Gene-Diabetes and Gene-Obesity Interaction Scan in 8,255 Cases and 11,900 Controls from PanScan and PanC4 Consortia. Cancer Epidemiol Biomarkers Prev. 2020 Sep;29(9):1784-1791. doi: 10.1158/1055-9965.EPI-20-0275. Epub 2020 Jun 16. PMID: 32546605; PMCID: PMC7483330.
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Cancer Epidemiol Biomarkers Prev. 2020 Sep;29(9):1784-1791. doi: 10.1158/1055-9965.EPI-20-0275. Epub 2020 Jun 16.

Genome-Wide Gene-Diabetes and Gene-Obesity Interaction Scan in 8,255 Cases and 11,900 Controls from PanScan and PanC4 Consortia.

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

Hongwei Tang, Lai Jiang, Rachael Z Stolzenberg-Solomon, Alan A Arslan, Laura E Beane Freeman, Paige M Bracci, Paul Brennan, Federico Canzian, Mengmeng Du, Steven Gallinger, Graham G Giles, Phyllis J Goodman, Charles Kooperberg, Loïc Le Marchand, Rachel E Neale, Xiao-Ou Shu, Kala Visvanathan, Emily White, Wei Zheng, Demetrius Albanes, Gabriella Andreotti, Ana Babic, William R Bamlet, Sonja I Berndt, Amanda Blackford, Bas Bueno-de-Mesquita, Julie E Buring, Daniele Campa, Stephen J Chanock, Erica Childs, Eric J Duell, Charles Fuchs, J Michael Gaziano, Michael Goggins, Patricia Hartge, Manal H Hassam, Elizabeth A Holly, Robert N Hoover, Rayjean J Hung, Robert C Kurtz, I-Min Lee, Núria Malats, Roger L Milne, Kimmie Ng, Ann L Oberg, Irene Orlow, Ulrike Peters, Miquel Porta, Kari G Rabe, Nathaniel Rothman, Ghislaine Scelo, Howard D Sesso, Debra T Silverman, Ian M Thompson, Anne Tjønneland, Antonia Trichopoulou, Jean Wactawski-Wende, Nicolas Wentzensen, Lynne R Wilkens, Herbert Yu, Anne Zeleniuch-Jacquotte, Laufey T Amundadottir, Eric J Jacobs, Gloria M Petersen, Brian M Wolpin, Harvey A Risch, Nilanjan Chatterjee, Alison P Klein, Donghui Li, Peter Kraft, Peng Wei

Affiliations

  1. Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
  2. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
  3. Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland.
  4. Department of Obstetrics and Gynecology, New York University School of Medicine, New York, New York.
  5. Department of Population Health, New York University School of Medicine, New York, New York.
  6. Department of Environmental Medicine, New York University School of Medicine, New York, New York.
  7. Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California.
  8. International Agency for Research on Cancer, Lyon, France.
  9. Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  10. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
  11. Lunenfeld-Tanenbaum Research Institute, Sinai Health System and University of Toronto, Toronto, Ontario, Canada.
  12. Division of Cancer Epidemiology, Cancer Council Victoria, Melbourne, Victoria, Australia.
  13. Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
  14. Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.
  15. SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  16. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  17. Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii.
  18. Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
  19. Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee.
  20. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
  21. Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland.
  22. Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  23. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  24. Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota.
  25. Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
  26. Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, the Netherlands.
  27. Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, United Kingdom.
  28. Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
  29. Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
  30. Department of Biology, University of Pisa, Pisa, Italy.
  31. Oncology Data Analytics Program, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
  32. Yale Cancer Center, New Haven, Connecticut.
  33. Department of Medicine, Yale School of Medicine, New Haven, Connecticut.
  34. Smilow Cancer Hospital, New Haven, Connecticut.
  35. Boston Veteran Affairs Healthcare System, Boston, Massachusetts.
  36. Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, Maryland.
  37. Gastroenterology, Hepatology, and Nutrition Service, Memorial Sloan Kettering Cancer Center, New York, New York.
  38. Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre, Madrid, Spain.
  39. CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.
  40. Hospital del Mar Institute of Medical Research (IMIM), Universitat Autònoma de Barcelona, Barcelona, Spain.
  41. CHRISTUS Santa Rosa Hospital - Medical Center, San Antonio, Texas.
  42. Department of Public Health, University of Copenhagen and Danish Cancer Society Research Center Diet, Genes and Environment, Copenhagen, Denmark.
  43. Hellenic Health Foundation, World Health Organization Collaborating Center of Nutrition, Medical School, University of Athens, Athens, Greece.
  44. Department of Epidemiology and Environmental Health, University of Buffalo, Buffalo, New York.
  45. Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut.
  46. Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
  47. Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. [email protected] [email protected] [email protected].
  48. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. [email protected] [email protected] [email protected].
  49. Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
  50. Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas. [email protected] [email protected] [email protected].

PMID: 32546605 PMCID: PMC7483330 DOI: 10.1158/1055-9965.EPI-20-0275

Abstract

BACKGROUND: Obesity and diabetes are major modifiable risk factors for pancreatic cancer. Interactions between genetic variants and diabetes/obesity have not previously been comprehensively investigated in pancreatic cancer at the genome-wide level.

METHODS: We conducted a gene-environment interaction (GxE) analysis including 8,255 cases and 11,900 controls from four pancreatic cancer genome-wide association study (GWAS) datasets (Pancreatic Cancer Cohort Consortium I-III and Pancreatic Cancer Case Control Consortium). Obesity (body mass index ≥30 kg/m

RESULTS: No genome-wide significant interactions (departures from a log-additive odds model) with diabetes or obesity were detected at the SNP level by the CC or CO approaches. The joint-effect test detected numerous genome-wide significant GxE signals in the GWAS main effects top hit regions, but the significance diminished after adjusting for the GWAS top hits. In the gene-based analysis, a significant interaction of diabetes with variants in the

CONCLUSIONS: This analysis did not find significant GxE interactions at the SNP level but found one significant interaction with diabetes at the gene level. A larger sample size might unveil additional genetic factors via GxE scans.

IMPACT: This study may contribute to discovering the mechanism of diabetes-associated pancreatic cancer.

©2020 American Association for Cancer Research.

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