Research Article Physical Activity and Pancreatic Cancer Risk among Urban Chinese: Results from Two Prospective Cohort Studies Lang Wu 1 , Wei Zheng 1 , Yong-Bing Xiang 2 , Yu-Tang Gao 2 , Hong-Lan Li 2 , Hui Cai 1 , and Xiao-Ou Shu 1 Abstract Background: Associations between physical activity and pan- creatic cancer risk are unclear. Methods: In two prospective cohort studies, the Shanghai Women's Health Study and Shanghai Men's Health Study, phys- ical activity and other information were collected at the baseline interview of 72,451 women and 60,037 men. Participants were followed up through annual linkage with a cancer registry in combination with in-person interviews taking place every 2 to 4 years. Results: We identified 225 female and 159 male cases during a median follow up of 16.1 and 10.3 years, respectively. Adult exercise participation was significantly associated with a decreased pancreatic cancer risk in men [hazard ratio (HR), 95% confidence interval (CI): 0.71 (0.50–1.00)]. Meeting the recommended min- imum exercise threshold to achieve health benefits of 150 min/ week of moderate-intensity or 75 min/week of vigorous-intensity exercise was associated with further decreased pancreatic cancer risk [HR (95% CI): 0.59 (0.40–0.87)]. We also observed an inverse association between adolescent physical activity and pancreatic cancer risk in men [HR (95% CI): 0.54 (0.33–0.90)]. Exercise throughout one's lifetime was associated with a 68% decrease in pancreatic cancer risk [HR (95% CI): 0.32 (0.16–0.66)]. No significant association was found in women. Adult non-exercise daily activity and occupational activity were not associated with pancreatic cancer risk in either men or women. Conclusions: Adult exercise and adolescent physical activity were significantly associated with a decreased pancreatic cancer risk in men but not in women. Impact: These findings underscore the importance of investi- gating the possible modification by sex on the exercise and pancreatic cancer risk association. Cancer Epidemiol Biomarkers Prev; 27(4); 479–87. Ó2018 AACR. Introduction Pancreatic cancer is the fourth leading cause of cancer mortality in the United States, with an estimated 43,090 deaths in 2017 (1). In China, there were 90,100 estimated new pancreatic cancer cases and 79,400 estimated deaths due to pancreatic cancer in 2015 (2). Most pancreatic cancers are already metastasized at diagnosis, resulting in a 5-year survival rate of only 7% (3). It is critical to better understand the risk factors and etiology of pancreatic cancer in order to identify effective prevention strategies to reduce its public health burden. The etiology of pancreatic cancer is largely unknown. Cigarette smoking (4, 5), type 2 diabetes (6, 7), family history of pancreatic cancer (8), and pancreatitis (9) are the few known risk factors for pancreatic cancer. Several epidemiologic studies suggest that physical activity may also be associated with risk of pancreatic cancer. For example, in the Japan Public Health Center-based Prospective Study, Inoue and colleagues observed that high levels of total physical activity were associated with decreased pancreatic cancer risk in men (10). With respect to leisure time physical activity (LTPA), a significant inverse association between high LTPA and pancreatic cancer risk was suggested in the Netherlands Cohort Study (11), the Canadian National Enhanced Cancer Surveillance System study among men (12), and a central Euro- pean multicenter case–control study (13). Isaksson and collea- gues also observed a significant inverse association between occupational physical activity (OPA) and pancreatic cancer risk in the Swedish Twin Registry study (14). Despite these observa- tions, however, a potential beneficial role of physical activity was not detected in many other studies (15, 16); in fact, one showed an opposite effect. In the College Alumni Health Study, moderate intensity physical activity was associated with increased risk of pancreatic cancer [RR (95% confidence intervals (CI): 1.37 (1.00– 1.87)] (17). It is possible that different types of physical activity, including LTPA, OPA, and daily living physical activity (DPA), may be associated with pancreatic cancer risk differentially; how- ever, few studies have systematically assessed their effects sepa- rately. Also, little is known as to whether physical activity during adolescence is associated with pancreatic cancer risk in later life. There is thus a critical need to conduct a study evaluating associa- tions of both adult and adolescent physical activity, including the different subtypes (LTPA, OPA, and DPA), to better characterize the relationship between physical activity and pancreatic cancer. The Shanghai Women's Health Study (SWHS) and the Shang- hai Men's Health Study (SMHS), two large population-based 1 Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee. 2 State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shang- hai Jiaotong University School of Medicine, Shanghai, China. Corresponding Author: Xiao-Ou Shu, Vanderbilt University Medical Center, 2525 West End Avenue, Suite 600 (IMPH), Nashville, TN 37203-1738. Phone: 615-936-0713; Fax: 615-936-8291; E-mail: xiao-ou.shu@vanderbilt.edu doi: 10.1158/1055-9965.EPI-17-0895 Ó2018 American Association for Cancer Research. Cancer Epidemiology, Biomarkers & Prevention www.aacrjournals.org 479 on May 21, 2020. © 2018 American Association for Cancer Research. cebp.aacrjournals.org Downloaded from Published OnlineFirst February 23, 2018; DOI: 10.1158/1055-9965.EPI-17-0895