Anthropometric Factors and Thyroid Cancer Risk by Histological Subtype: Pooled Analysis of 22 Prospective Studies

Cari M Kitahara, Marjorie L McCullough, Silvia Franceschi, Sabina Rinaldi, Alicja Wolk, Gila Neta, Hans Olov Adami, Kristin Anderson, Gabriella Andreotti, Laura E Beane Freeman, Leslie Bernstein, Julie E Buring, Francoise Clavel-Chapelon, Lisa A De Roo, Yu-Tang Gao, J Michael Gaziano, Graham G Giles, Niclas Håkansson, Pamela L Horn-Ross, Vicki A Kirsh, Martha S Linet, Robert J MacInnis, Nicola Orsini, Yikyung Park, Alpa V Patel, Mark P Purdue, Elio Riboli, Kimberly Robien, Thomas Rohan, Dale P Sandler, Catherine Schairer, Arthur B Schneider, Howard D Sesso, Xiao-Ou Shu, Pramil N Singh, Piet A van den Brandt, Elizabeth Ward, Elisabete Weiderpass, Emily White, Yong-Bing Xiang, Anne Zeleniuch-Jacquotte, Wei Zheng, Patricia Hartge, Amy Berrington de González

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. In this large pooled analysis of 22 prospective studies (833,176 men and 1,260,871 women), we investigated thyroid cancer incidence associated with greater height, body mass index (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. During follow-up, 2,996 incident thyroid cancers and 104 thyroid cancer deaths were identified. All anthropometric factors were positively associated with thyroid cancer incidence: HRs (95% 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-interaction=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. Our 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.