Longitudinal body mass index-derived exposures and risk of 26 types of cancer: a cohort study of 2.6 million adults in catalonia

Abstract

Background/Objectives: Single measurements of body mass index (BMI) have been associated with increased risk of several cancers. Whether different adiposity exposures over the life course are more relevant cancer risk factors than BMI remains unclear. Our objective was to investigate the association between baseline BMI and longitu-dinal BMI-derived exposures during early adulthood in relation to the risk of 26 cancers.Methods: We conducted a population-based cohort study with electronic health records from Catalonia, Spain, from 2009 to 2018. We included 2,645,885 individuals aged ≥ 40 years and free of cancer on 01/01/2009. We multiply imputed BMI at several ages to compute BMI trajectories using a linear mixed-effects model. With the trajec-tories, we calculated baseline BMI and six longitudinal BMI-derived exposures for overweight and obesity (duration of, cumulative expo-sure to, and age of onset of BMI ≥ 25 and ≥ 30 kg/m2, respectively) between 18 and 40 years, and we investigated the association of each of them with risk of 26 cancers. We fitted Cox proportional hazard models, with one exposure at a time (adjusted by sex, nationality, socioeconomic status, smoking status, alcohol intake, and stratifed by age). We calculated the hazard ratios (HR) for each cancer type per 1 standard deviation (SD) increment of each exposure. We further re-stricted the analyses to never smokers.Results: After a median of 10 years of follow-up, 225,396 (9%) par-ticipants were diagnosed with cancer. The median age was 56 years, BMI at baseline was 28 kg/m2, and 47% were males. Baseline BMI and the six longitudinal BMI-derived exposures were positively related to the risk of cancers of the corpus uteri, kidney, gallbladder and biliary tract, thyroid, postmenopausal breast, leukemia, multiple myeloma, brain, colorectal, liver (in descending order of HRs of baseline BMI) and, among never smokers, of head and neck and bladder. Longitudi-nal exposures were also positively associated with risk of ovary, non-Hodgkin lymphoma, malignant melanoma of skin, prostate, pancreas, and stomach cancers. Some exposures were inversely associated with stomach and respiratory tract cancer risk, but those associations dis-appeared in never smokers-restricted analyses.Conclusions/Recommendations: Elevated body fatness during early adulthood and longer duration of adiposity increases the risk of 18 cancers (including cancers not yet associated with baseline BMI). Our findings support public health strategies to prevent and reduce early overweight and obesity for cancer prevention.