Abstract Background: Pancreatic cancer (PC) is one of the deadliest malignancies. Lab based research suggests that two types of polyunsaturated fatty acids (PUFA), n-3 and n-6 PUFA, may have opposing effects on PC carcinogenesis. However, human evidence on the role of dietary PUFA intake in PC risk is inconsistent. Previous epidemiological studies on this topic were conducted primarily among Whites and included few individuals from low socioeconomic status (SES). The exposure patterns of n-3 and n-6 PUFA differ across racial groups, with African Americans (AAs) in the high end and Asians in the low end of range. To better characterize the associations of PUFA with PC risk, we conducted a nested case-control study focusing on understudied Asians and low SES AAs and Whites. Methods: We performed a nested case-control study within three population-based prospective cohort studies: the Shanghai Women’s Health Study (SWHS), Shanghai Men’s Health Study (SMHS), and Southern Community Cohort Study (SCCS). Dietary PUFA intakes and other variables were collected from the baseline dietary and other questionnaires. Participants were followed up through annual linkage to cancer registries. Controls were matched to cases on age, sex, and blood sample availability in SWHS/SMHS, and age, sex, race, and enrollment location in SCCS, using incidence density sampling (case-to-control ratio:1:4). Included in the study are 244 cases and 973 controls of Asian females in SWHS, 189 cases and 755 controls of Asian males in SMHS, and 307 cases and 1,228 controls in SCCS (including 219 cases and 876 controls of AAs). The PUFA intake was adjusted for total energy intake using the residual method. Conditional logistic regression analyses were performed to estimate the association of PC risk with dietary PUFA consumption after adjusting for potential covariates. Results: The average dietary intake (mean ± SD; g/day) of n-3 and n-6 PUFA were 1.0 ± 0.5 and 6.3 ± 3.1, 1.1 ± 0.5 and 7.2 ± 3.0, and 2.0 ± 1.2 and 19.3 ± 11.7 in the controls of SWHS, SMHS and SCCS, respectively. We observed that in Chinese men, high intakes of certain n-3 PUFA were significantly associated with increased PC risk. The adjusted odds ratio (OR) (95% confidence interval (CI)) comparing the highest versus lowest quartile of docosapentaenoic acid (DPA) was 1.79 (1.10-2.93), with a p for trend across quartiles of 0.02. For docosahexaenoic acid (DHA), the OR 4th vs. 1st quartile (95% CI) = 1.71 (1.06-2.78) (p for trend = 0.04). For marine n-3 PUFA, the OR 4th vs. 1st quartile (95% CI) = 1.69 (1.03-2.76) (p for trend = 0.04). There was no significant association for n-6 PUFA. No significant association was observed for n-3 or n-6 PUFA with PC risk in SWHS or SCCS. Conclusions: In a nested case-control study, we observed that in Chinese men, the dietary intake of overall marine n-3 PUFA, DPA, and DHA were positively associated with PC risk. Such associations were not observed in Chinese women or low SES AAs/Whites. Citation Format: Lang Wu, Wei Zheng, William J. Blot, Mark D. Steinwandel, Wanqing Wen, Yong-Bing Xiang, Yu-Tang Gao, Hong-Lan Li, Rachael Stolzenberg-Solomon, Harvey J. Murff, Xiao-Ou Shu. Dietary polyunsaturated fatty acids intake and pancreatic cancer risk in understudied populations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 639.