Abstract 853: Body mass index trajectories across the adult life course and pancreatic cancer risk

Background: Adiposity is associated with pancreatic ductal adenocarcinoma (PDAC), but the effects of weight excess over an adult life course have not been studied extensively. We examined the association between trajectories of body mass index (BMI) from ages 18 up to 71 years and risk of subsequent PDAC. Methods: Our analysis included 270,722 (163,873 men, 106,849 women) NIH-AARP Diet and Health Study participants, 50-71y, who successfully completed questionnaires with self-reported height and weight at ages 18, 35, 50 and at baseline (50-71y, 1995-1996) and from which BMI (kg/m2) was calculated. We used latent class growth mixture modeling to identify BMI trajectories using adult BMI reported at each of the four timepoints. We identified BMI trajectories for all sample combined and separately for men and women. We then examined the association between BMI trajectories and incident PDAC using Cox proportional hazards models to calculate age, smoking, and sex adjusted hazard ratios (HR) and 95% confidence intervals (CI) overall and by sex. Participants that maintained normal weight status over their adulthood were set as the referent group. Results: Over an average follow-up time of 13.1 years (max: 15.17 years), 3105 incident PDAC cases (2033 men, 1072 women) were identified in the overall cohort. We identified four overall and sex specific BMI trajectory groups, each with one maintainer and three increasers. Participants either maintained normal weight (N-N, 37.1% of the cohort), or increased from normal-overweight (N-OW, 36.4%), normal-obese (N-O, 20.7%), or normal-severely obese (N-SO, 5.8%). The male cohort was divided into N-N (35.5%), N-OW (23.3%), normal-higher overweight (N-HOW, 34.8%), and N-SO (6.6%) while the female cohort was divided into N-N (51.6%), N-OW (34.5%), N-SO (11.3%), and OW-SO (2.7%). Compared to N-N, the N-OW (HR=1.12, 95% CI 1.03-1.21), N-O (1.22, 1.11-1.35) and N-SO (1.22, 1.04-1.45) groups were at significantly increased risk for PDAC. Compared to the sex-specific maintainer groups, men in the N-OW (1.14, 1.02-1.28), N-HOW (1.16, 1.04-1.29), and N-SO (1.39, 1.15-1.67) groups were significantly associated with PDAC, while only women in the N-OW (1.12, 1.00-1.29) group showed a borderline significant association. Adding diabetes to the models slightly attenuated the associations by less than 10% with the greatest attenuation observed in the SO groups. The overall associations were not significantly modified by sex (P-interaction = 0.10) or smoking status (never, former, current, P-interaction = 0.17). Conclusions: In this large prospective cohort study, increasing BMI throughout adulthood was associated with a greater risk for PDAC. Citation Format: Simran Arjani, Pedro F. Saint-Maurice, Sachelly Julian-Serrano, Rachael Stolzenberg-Solomon. Body mass index trajectories across the adult life course and pancreatic cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 853.