Body mass index and risk of over 100 cancer forms and subtypes in 4.1 million individuals in Sweden: the Obesity and Disease Development Sweden (ODDS) pooled cohort study
Ming Sun, Marisa da Silva, Tone Bjørge, Josef Fritz, Innocent B. Mboya, Mats Jerkeman, Pär Stattin, Jens Wahlström, Karl Michaëlsson, Bethany Van Guelpen, Patrik K. E. Magnusson, Sven Sandin, Weiyao Yin, Ylva Trolle Lagerros, Weimin Ye, Bright I. Nwaru, Hannu Kankaanranta, Lena Lönnberg, Abbas Chabok, Karolin Isaksson, Nancy L. Pedersen, Sölve Elmståhl, Lars Lind, Linnéa Hedman, Christel Häggström, Tanja Stocks
Abstract
Background Obesity, assessed by body mass index (BMI), is an established risk factor for 13 cancers. We aimed to identify further potential obesity-related cancers and to quantify their association with BMI relative to that of established obesity-related cancers. Methods Using Cox regression models on 4,142,349 individuals in Sweden (mean age 27.1 years at weight measurement), we calculated hazard ratios (HRs) for the association between BMI and the risk of 122 cancers and cancer subtypes, grouped by topography and morphology. Cancers with a positive association (i.e., HR >1) at an α-level of 0.05 for obesity (BMI ≥30 kg/m 2 ) vs. normal weight (BMI 18.5–24.9 kg/m 2 ) or per 5 kg/m 2 higher BMI, for which obesity is not an established risk factor, were considered potentially obesity related. Findings After 100.2 million person-years of follow-up, 332,501 incident cancer cases were recorded. We identified 15 cancers in men and 16 in women as potentially obesity related. These were cancers of the head and neck, gastrointestinal tract, malignant melanoma, genital organs, endocrine organs, connective tissue, and haematological malignancies. Among these, there was evidence of differential associations with BMI between subtypes of gastric cancer, small intestine cancer, cervical cancer, and lymphoid neoplasms (P values for heterogeneity in HRs <0.05). The HR (95% confidence interval) per 5 kg/m 2 higher BMI was 1.17 (1.15–1.20) in men and 1.13 (1.11–1.15) in women for potential obesity-related cancers (51,690 cases), and 1.24 (1.22–1.26) in men and 1.12 (1.11–1.13) in women for established obesity-related cancers (84,384 cases). Interpretation This study suggests a large number of potential obesity-related cancers could be added to already established ones. Importantly, the magnitudes of the associations were largely comparable to those of the already established obesity-related cancers. We also provide evidence of specific cancer subtypes driving some associations with BMI. Studies accounting for cancer-specific confounders are needed to confirm these findings. Funding Swedish Research Council, Swedish Cancer Society, Mrs. Berta Kamprad's Cancer Foundation, Crafoord Foundation, Cancer Research Foundation at the Department of Oncology, Malmö University Hospital, and China Scholarship Council.