Abstract Pancreatic cancer is the third-leading cause of cancer-related deaths in both men and women in the United States and has the lowest 5-year survival rate among all common cancers. The etiology of pancreatic cancer virtually remains elusive, with cigarette smoking and family history as the only well-established risk factors. Therefore, it is critical to identify lifestyle and other modifiable risk factors to reduce incidence and mortality of pancreatic cancer. It is biologically plausible that overweight and obesity modulate the risk of pancreatic cancer as they induce chronic inflammation and promote the occurrence of type-2 diabetes. However, previous studies on the association between longitudinal changes in weight status and pancreatic cancer risk are inconsistent. The present study was conducted to investigate the association between lifetime trajectory of body mass index (BMI) and risk of pancreatic cancer among participants in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. BMI (kg/m2) was calculated from self-reported body weight and height of the participants at age 20, age 50, and time of entry into the cohort (ages 55-74). Of 148,447 men and women who completed a valid baseline questionnaire, 711 developed pancreatic cancer during a median follow-up period of 12 years. Using SAS Proc Traj, we identified 5 BMI trajectory groups: normal-steady, normal-overweight-normal, normal-overweight, normal-obese, and overweight-obese. Normal weight, overweight, and obesity were defined as BMI≤25, 25<BMI<30, and BMI≥30, respectively. Hazard ratios (HR) and 95% confidence intervals (CI) for pancreatic cancer risk in relation to BMI trajectory group were estimated using Cox proportional hazards regression. After adjustment for age, sex, race, family history of pancreatic cancer, cigarette smoking, and randomization, BMI trajectory was not significantly associated with pancreatic cancer risk. Compared with normal-steady group, HRs (95% CIs) were 1.09, (0.73, 1.62), 0.99 (0.79, 1.25), 1.02 (0.84, 1.23), and 1.21 (0.95, 1.54) for normal-overweight-normal, normal-overweight, normal-obese, and overweight-obese groups, respectively. However, a marginally increased risk of pancreatic cancer was observed for overweight-obese group when analysis was confined to localized and surgically resectable tumor [1.52 (0.97, 2.67)] and metastatic tumor [1.33 (0.99, 1.80)]. Subjects who were overweight at age 20 exhibited an increased risk of pancreatic cancer [1.23 (1.00, 1.52)] compared with those who had a normal weight at the same age. Similar results were not obtained for weight status reflected by BMI at age 50 and study enrollment. In conclusion, the present study reveals that lifetime BMI trajectory does not significantly alter pancreatic cancer risk but suggests that overweight early in life may confer an elevated risk for this fatal malignancy. Citation Format: Jianjun Zhang, Margaret Hoyt. Lifetime body mass index trajectory and pancreatic cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5746.
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