Abstract 4811: Dietary folate intake and pancreatic cancer risk: Results from the European Prospective Investigation into Cancer and Nutrition.
Authors: Park Jin Young , Bueno-de-Mesquita H.B(as) , Ferrari Pietro , Vineis Paolo , Weiderpass Elisabete , Slimani Nadia ,   for the EPIC Study Group
Published: August 2014

Abstract
Background: Pancreatic cancer (PC) has an exceptionally high mortality rate due to late discovery and poor prognosis. The etiology of the cancer is largely unknown and primary prevention strategies are limited for this lethal cancer. Over the past years, evidence has been accumulated for folate which may play a role in carcinogenesis. Previous epidemiological studies, however, have shown inconsistent results in relation to PC risk with a weak inverse association with folate intake from foods, but not from supplements. The recent large study from the Pooling Project found no association between folate intake and PC risk. However, in the pooled analysis, folate data may be heterogeneous across studies and countries, thus not readily comparable. In the EPIC study, we obtained dietary folate intake data that was standardized across 10 participating countries using the EPIC Nutrient DataBase. Folic acid fortification or supplementation use was not common in Europe at the baseline data collection. We then set out to evaluate the association between total dietary folate intake and PC risk.
Methods: A total of 477,245 participants without any history of cancer and with complete dietary folate information ascertained by food frequency questionnaire were followed up for 11 years, during which 904 first incident primary PC cases were recorded. Folate intake was energy-adjusted by using the residual method. Hazard Ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models.
Results: In multivariable analyses stratified by age, sex, study center and adjusted for smoking status, energy intake, BMI, educational level, diabetes status, supplement use and dietary fiber intake, we observed non-significantly decreased PC risk with higher folate intake: the HR of PC risk for those in the highest quartile of folate intake (≥353 μg/d) compared with the lowest quartile (&lt;240 μg/d) was 0.65 (95% CI: 0.37, 1.13; Ptrend = 0.13). There was a borderline significant and positive trend in PC risk across folate quartiles among current smokers (HR=1.53 (0.59-3.97) for 240-291 μg/d, 3.51 (1.04-11.90) for 291-353 μg/d, and 3.31 (0.71-15.40) for ≥353 μg/d of folate intake, respectively (Ptrend = 0.07)). A similar pattern was shown when a single reference category was chosen and joint effects were determined for tertiles of folate in combination with smoking categories in relation to PC risk. When very low (&lt;150 μg/d) or high intake (≥500 μg/d) were investigated using 200-300 μg/d as a reference, we found a slightly increased, but statistically non-significant risk estimate with a very low intake (HR=1.28, 95% CI: 0.40-4.06).
Conclusions: We found non-significant inverse associations between dietary folate intake and PC risk in the large European study. There was some evidence that the findings were heterogeneous by smoking status. Our results warrant further investigation.
Citation Format: Jin Young Park, H.B(as) Bueno-de-Mesquita, Pietro Ferrari, Paolo Vineis, Elisabete Weiderpass, Nadia Slimani, for the EPIC Study Group. Dietary folate intake and pancreatic cancer risk: Results from the European Prospective Investigation into Cancer and Nutrition. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4811. doi:10.1158/1538-7445.AM2013-4811