• Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
• Department of Hepatobiliary Surgery, The People's Hospital of Dazu district, Chongqing, China.
• Department of Breast and Endocrine Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
• Pediatric Surgery Center, Qingdao Women and Children's Hospital, Qingdao University, Qingdao, Shandong, China.
• Department of Nutrition and Food Hygiene, School of Public Health and Management, Chongqing Medical University, Chongqing, China.
• Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China. gongjianping@cqmu.edu.cn.

BACKGROUND: Total antioxidant capacity (TAC) reflects an individual's overall antioxidant intake. We sought to clarify whether higher TAC is associated with lower risks of pancreatic cancer incidence and mortality in the U.S. general population.

METHODS: A total of 96,018 American adults were identified from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. A ferric-reducing ability of plasma score was used to reflect an individual's TAC intake from diet and/or supplements. Cox regression was used to calculate hazard ratios (HR) for pancreatic cancer incidence, and competing risk regression was used to calculate subdistribution HRs for pancreatic cancer mortality. Restricted cubic spline regression was used to test nonlinearity.

RESULTS: A total of 393 pancreatic cancer cases and 353 pancreatic cancer-related deaths were documented. Total (diet + supplements) TAC was found to be inversely associated with pancreatic cancer incidence (HR _{quartile 4 vs. quartile 1} = 0.53; 95% confidence interval, 0.39-0.72; P _trend = 0.0002) and mortality (subdistribution HR _{quartile 4 vs. quartile 1} = 0.52; 95% confidence interval 0.38-0.72; P _trend = 0.0003) in a nonlinear dose-response manner (all P _nonlinearity < 0.01). Similar results were observed for dietary TAC. No association of supplemental TAC with pancreatic cancer incidence and mortality was found.

CONCLUSIONS: In the U.S. general population, dietary but not supplemental TAC level is inversely associated with risks of pancreatic cancer incidence and mortality in a nonlinear dose-response pattern.

IMPACT: This is the first prospective study indicating that a diet rich in antioxidants may be beneficial in decreasing pancreatic cancer incidence and mortality.