PWE-009 Dietary docosahexaenoic acid is inversely associated with the risk of developing oesophageal adenocarcinoma: a UK prospective study in the EPIC-Norfolk cohort, using information from 7-day food diaries

Abstract

Introduction. Dietary docosahexaenoic acid (DHA) and eicosapentanaenoic acid (EPA) are both n-3 polyunsaturated fatty acids (n3 PUFAs) which have both anti-inflammatory and anti-carcinogenic actions, including inhibiting angiogenesis and tumour cell proliferation, and promoting apoptosis. The aim of this study was to conduct the first epidemiological investigation, using information from food diaries, the most accurate form of nutritional assessment in such work, to determine if there is an inverse association between DHA and EPA intake and the risk of developing both Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). Methods. A total of 25 639 men and women aged 40-75 years, were recruited between the years 1993-1997 into the European Prospective Investigation into Cancer (EPIC)-Norfolk cohort Study. At baseline, participants completed detailed 7 day food diaries which were then coded by nutritionists using a specially designed computer programme containing information on 55 000 food items. Subjects were then followed up over subsequent years for the development of BE and EAC. A review of case notes confirmed these diagnoses. Dietary intake of n3 PUFAs were compared between cases and a random sample of 3 797 controls, whose diaries had been coded, in a case-cohort analysis. Intakes were divided into quintiles and both biological gradients and threshold effects were calculated. Cox regression estimated the hazard ratios (HR) for both DHA and EPA, adjusted for age, gender, BMI, smoking, alcohol, and arachidonic acid intake. Results. During follow-up, 104 patients were diagnosed with BE (80% men, median age 67.0 yrs [IQR=61.1-73.1] at diagnosis) after a median follow-up of 6.2 yrs (IQR=4.1-8.1). A further 63 patients developed EAC (83% men, median age 73.0 yrs [IQR=67.0-78.0] at diagnosis) after a median followup of 6.4 yrs (IQR=4.4-8.9). For EAC, there was a large significant inverse association, in a threshold manner, comparing the lowest quintile with a summation of the top four quintiles of dietary intake, for DHA (HR=0.47, 95% CI=0.25-0.88, p=0.02). EPA (HR=0.60, 95% CI=0.31-1.15, p=0.12) intake was not significantly associated with EAC. For BE, no significant associations were found with either dietary DHA (HR=0.69, 95% CI=0.40-1.20, p=0.19) or EPA (HR=1.03, 95% CI= 0.56-1.90, p=0.93). No gradient effects across quintiles were seen for either BE or EAC. Adjustment for total energy intake did not significantly alter associations. Conclusion. Dietary DHA was associated with an approximate 50% risk reduction for EAC, although there was none for BE. The data support a role for dietary DHA in preventing the malignant transformation of BE to EAC, and therefore should be measured in future aetiological studies of EAC.