Background: Greater height and body mass index (BMI) have been associated with an increased risk of thyroid cancer, particularly papillary carcinoma, the most common and least aggressive subtype. Few studies have evaluated these associations in relation to other, more aggressive histologic types or thyroid cancer-specific mortality. Methods: This large pooled analysis of 22 prospective studies (833,176 men and 1,260,871 women) investigated thyroid cancer incidence associated with greater height, BMI at baseline and young adulthood, and adulthood BMI gain (difference between young-adult and baseline BMI), overall and separately by sex and histological subtype using multivariable Cox proportional hazards regression models. Associations with thyroid cancer mortality were investigated in a subset of cohorts (578,922 men and 774,373 women) that contributed cause of death information. Results: During follow-up, 2996 incident thyroid cancers and 104 thyroid cancer deaths were identified. All anthropometric factors were positively associated with thyroid cancer incidence: hazard ratios (HR) [confidence intervals (CIs)] for height (per 5 cm) = 1.07 [1.04-1.10], BMI (per 5 kg/m2) = 1.06 [1.02-1.10], waist circumference (per 5 cm) = 1.03 [1.01-1.05], young-adult BMI (per 5 kg/m2) = 1.13 [1.02-1.25], and adulthood BMI gain (per 5 kg/m2) = 1.07 [1.00-1.15]. Associations for baseline BMI and waist circumference were attenuated after mutual adjustment. Baseline BMI was more strongly associated with risk in men compared with women (p = 0.04). Positive associations were observed for papillary, follicular, and anaplastic, but not medullary, thyroid carcinomas. Similar, but stronger, associations were observed for thyroid cancer mortality. Conclusion: The results suggest that greater height and excess adiposity throughout adulthood are associated with higher incidence of most major types of thyroid cancer, including the least common but most aggressive form, anaplastic carcinoma, and higher thyroid cancer mortality. Potential underlying biological mechanisms should be explored in future studies.
Bibliographical noteFunding Information:
COSM and SMC: These cohorts are supported by the Swedish Research Council, the Swedish Cancer Foundation, and by Strategic Funds from Karolinska Institutet, Stockholm, Sweden. CPS-II: The American Cancer Society funds the creation, maintenance, and updating of the Cancer Prevention Study-II (CPS-II) cohort. CTS: The CTS is supported by grant R01 CA77398 from the National Cancer Institute. The collection of cancer incidence data used in the CTS is supported by the California Department of Public Health (CDPH) as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885; the NCI’s SEER program under contract HHSN261201000140C awarded to the Cancer Prevention Institute of California, contract HHSN261201000035C awarded to the University of Southern California, and contract HHSN261201000034C awarded to the Public Health Institute; and the Centers for Disease Control and Prevention’s (CDCP) National Programof Cancer Registries, under agreement U58DP003862-01 awarded to the CDPH. The ideas and opinions expressed herein are those of the author(s) and endorsement by the CDPH, NCI, and CDCP or their contractors and subcontractors is not intended nor should be inferred. EPIC: The authors are grateful to the support of the World Cancer Research Fund (2009/92). The coordination of EPIC is financially supported by the European Commission (DGSANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society, Denmark; Ligue Contre le Cancer, France; Institut Gustave Roussy, France; Mutuelle Generale de l’Education Nationale, France; Institut National de la Sante et de la Recherche Medicale, France; Deutsche Krebshilfe, Germany, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research, Germany; Hellenic Health Foundation, Greece; Italian Association for Research on Cancer; National Research Council, Italy; Dutch Ministry of Public Health, Welfare and Sports, the Netherlands; Netherlands Cancer Registry, the Netherlands; LK Research Funds, the Netherlands; Dutch Prevention Funds, the Netherlands; Dutch ZON (Zorg Onderzoek Nederland), the Netherlands; World Cancer Research Fund, London, UK; Statistics Netherlands, the Netherlands; European Research Council, Norway; Health Research Fund, Regional Governments of Andalucia, Asturias, Basque Country, Murcia (project no. 6236) and Navarra, ISCIII RETIC (RD06/0020/0091), Spain; Swedish Cancer Society, Sweden; Swedish Scientific Council, Sweden; Regional Government of Skane and Vasterbotten, Sweden; Cancer Research United Kingdom; Medical Research Council, United Kingdom; Stroke Association, United Kingdom, British Heart Foundation, United Kingdom; Department of Health, Food Standards Agency, United Kingdom; and Wellcome Trust; United Kingdom. We thank Bertrand Hemon for his precious help with the EPIC database. The principle investigators and funders corresponding to each of the EPIC centers that contributed cases were Kim Overvad, Anne Tjonneland (Denmark); Francoise Clavel-Chapelon (France); Heiner Boeing, Rudolf Kaaks (Germany); Antonia Trichopoulou (Greece); Vittorio Krogh, Domenico Palli, Paolo Vineis, Salvatore Panico, Rosario Tumino (Italy); Eiliv Lund (Norway); Antonio Agudo, Maria Jose Sanchez, J.Ramón Quirós, Carmen Navarro, Aurelio Barricarte, Miren Dorronsoro (Spain); Mattias Johansson, Jonas Manjer (Sweden); H. Bas Bueno-de-Mesquita, Petra H. Peeters (The Netherlands); Timothy Key, Nick Wareham (UK); The coordination of European Prospective Investigation into Cancer and Nutrition is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by the French National Cancer Institute (L’Institut National du Cancer; INCA); Grant Number: 2009-139; Ligue contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid; German Cancer Research Center (DKFZ); German Federal Ministry of Education and Research; Danish Cancer Society; Health Research Fund (FIS) of the Spanish Ministry of Health (RTICC (DR06/0020/0091); the participating regional governments from Asturias, Andalucía, Murcia, Navarra and Vasco Country and the Catalan Institute of Oncology of Spain; Cancer Research UK; Medical Research Council, UK; the Stroke Association, UK; British Heart Foundation; Department of Health, UK; Food StandardsAgency, UK; the Wellcome Trust, UK; the Hellenic Health Foundation; Italian Association for Research on Cancer; Compagnia San Paolo, Italy; Dutch Ministry of Public Health, Welfare and Sports; Dutch Ministry of Health; Dutch Prevention Funds; LK Research Funds; Dutch ZON (Zorg Onderzoek Nederland); World Cancer Research Fund (WCRF); Statistics Netherlands (The Netherlands); Swedish Cancer Society; Swedish Scientific Council; Regional Government of Skane, Sweden; Nordforsk—Centre of Excellence programme. IWHS: The authors thank the study participants. IWHS is funded by a grant from the National Cancer Institute (R01 CA39742). Melbourne Collaborative Cohort Study: This study was made possible by the contribution of many people, including the original investigators and the diligent team who recruited the participants and who continue working on follow-up. We would also like to express our gratitude to the many thousands of Melbourne residents who continue to participate in the study. This work was supported by infrastructure from Cancer Council Victoria and grants from the National Health and Medical Research Council of Australia 209057 and 251533. PHS: This study is supported by grants from the National Cancer Institute (CA-34933, CA-40360, and CA-097193) and from the National Heart, Lung, and Blood Institute (HL-26490 and HL-34595), National Institutes of Health, Bethesda, MD. The Sister Study is supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (ZO1-ES-044005). Support for data collection and study and data management are provided by Social & Scientific Systems, Inc., and Westat, Inc., Durham, NC. Aimee D’Aloisio, Sandra Halverson, Dan Scharf, and David Shore helped prepare the data for this analysis. The SWHS and SMHS are supported in part by research grants from the National Cancer Institute (R37 CA070867, UM1 CA182910, R01 CA082729, and UM1 CA173640). The authors thank participants and research staff members of the studies for their contribution. USRT: The authors thank the study participants and Jerry Reid of the American Registry of Radiologic Technologists for their continued support of this study; Diane Kampa and Allison Iwan of the University of Minnesota for study management and data collection; and Jeremy Miller at Information Management Services, Inc., for biomedical computing support. VITAL: Emily White was supported by the grant K05-CA154337 (National Cancer Institute and Office of Dietary Supplements).