Risk factors for cancers of unknown primary site: Results from the prospective EPIC cohort |
| |
| Authors: | Rudolf Kaaks,Disorn Sookthai,Kari Hemminki,Alwin Kr mer,Heiner Boeing,Elisabet Wirf lt,Elisabete Weiderpass,Kim Overvad,Anne Tj nneland,Anja Olsen,Petra H. Peeters,H. B Bueno‐de‐Mesquita,Salvatore Panico,Valeria Pala,Paolo Vineis,J. Ram n Quir s,Eva Ardanaz,Marí a‐Jos S nchez,Maria‐Dolores Chirlaque,Nerea Larra aga,Paul Brennan,Dimitrios Trichopoulos,Antonia Trichopoulou,Pagona Lagiou,G ran Hallmans,Kay‐Tee Khaw,Timothy J. Key,Elio Riboli,Federico Canzian |
| |
| Affiliation: | 1. Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), , Heidelberg, Germany;2. Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), , Heidelberg, Germany;3. Center for Primary Health Care Research, Lund University, , Malm?, Sweden;4. Clinical Cooperation Unit, Molecular Hematology and Oncology, German Cancer Research Center (DKFZ), , Heidelberg, Germany;5. Department of Internal Medicine V, University of Heidelberg, , Heidelberg, Germany;6. Department of Epidemiology, German Institute of Human Nutrition (DIfE) Potsdam‐Rehbrücke, , Nuthetal, Germany;7. Department of Clinical Sciences, Lund University, , Malm?, Sweden;8. Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, , Troms?, Norway;9. Department of Research, Cancer Registry of Norway, , Oslo, Norway;10. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, , Stockholm, Sweden;11. Samfundet Folkh?lsan, , Helsinki, Finland;12. Department of Public Health, Section for Epidemiology, Aarhus University, , Aarhus, Denmark;13. Danish Cancer Society Research Center, , Copenhagen, Denmark;14. Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center, , Utrecht, The Netherlands;15. Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, , London, United Kingdom;16. National Institute for Public Health and the Environment (RIVM), , Bilthoven, The Netherlands;17. Department of Gastroenterology and Hepatology, University Medical Centre, , Utrecht, The Netherlands;18. Department of Clinical and Experimental Medicine, Federico II University, , Naples, Italy;19. Department of Preventive & Predictive Medicine, Nutritional Epidemiology Unit, Fondazione IRCCS Istituto, Nazionale dei Tumori, , Milan, Italy;20. Human Genetics Foundation (HuGeF), , Torino, Italy;21. Public Health Directorate, , Asturias, Spain;22. Navarre Public Health Institute, , Pamplona, Spain;23. CIBER Epidemiology and Public Health CIBERESP, , Spain;24. Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria de Granada (Granada.ibs), , Granada, Spain;25. Department of Epidemiology, Murcia Regional Health Authority, , Murcia, Spain;26. Public Health Division of Gipuzkoa, Department of Health of the regional Government of the Basque Country, , San Sebastian, Spain;27. Section of Genetics, International Agency for Research on Cancer (IARC), , Lyon, France;28. Hellenic Health Foundation, , Athens, Greece;29. Department of Epidemiology, Harvard School of Public Health, , Boston, MA;30. Bureau of Epidemiologic Research, Academy of Athens, , Athens, Greece;31. Department of Hygiene, Epidemiology and Medical Statistics, WHO Collaborating Center for Food and Nutrition Policies, University of Athens Medical, , Greece;32. Department of Public Health and Clinical Medicine/Nutritional Research, Ume? University, , Ume?, Sweden;33. School of Clinical Medicine, University of Cambridge, , Cambridge, United Kingdom;34. Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, , United Kingdom;35. Genomic Epidemiology Group, German Cancer Research Center (DKFZ), , Heidelberg, Germany |
| |
| Abstract: | Cancer of unknown primary site (CUP) may be called an “orphan” disease, as it is diagnosed when metastases are detected while the primary tumor typically remains undetected, and because little research has been done on its primary causes. So far, few epidemiological studies, if any, have addressed possible risk factors for CUP. We analyzed data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (N = 476,940). During prospective follow‐up, a total of 651 cases of incident cases of CUP were detected (ICD‐O‐2 code C809). Proportional hazards models were conducted to examine the associations of lifetime history of smoking habits, alcohol consumption, levels of education and anthropometric indices of adiposity with risk of being diagnosed with CUP. Risk of being diagnosed with CUP was strongly related to smoking, with a relative risk of 3.66 [95% C.I., 2.24–5.97] for current, heavy smokers (26+ cigarettes/day) compared to never smokers (adjusted for alcohol consumption, body mass index, waist circumference and level of education) and a relative risk of 5.12 [3.09–8.47] for cases with CUP who died within 12 months. For alcohol consumption and level of education, weaker associations were observed but attenuated and no longer statistically significant after adjusting for smoking and indices of obesity. Finally, risk of CUP was increased by approximately 30 per cent for subjects in the highest versus lowest quartiles of waist circumference. Our analyses provide further documentation, in addition to autopsy studies, that a substantial proportion of cancers of unknown primary site may have their origin in smoking‐related tumors, in particular. |
| |
| Keywords: | cancer of unknown primary site (CUP) prospective cohort study smoking alcohol obesity waist circumference |
|
|
