A 24-year prospective study of dietary α-linolenic acid and lethal prostate cancer

Several meta-analyses have attempted to determine the relationships between intake of α-linolenic acid (ALA) and prostate cancer, but results were inconclusive. 47,885 men aged 40-75 years without prior cancer in the Health Professionals Follow-Up Study were prospectively followed from 1986 to 2010. Intake of ALA was determined from validated food frequency questionnaires every 4 years. We used multivariate Cox proportional hazards models to estimate hazard ratios (HR) with 95% confidence intervals (CIs) for lethal prostate cancer (distant metastasis or prostate cancer death). 386 lethal prostate cancers were diagnosed in the pre-PSA era (before February, 1994) and 403 cancers in the PSA era. Intake of ALA was associated with increased risk of lethal prostate cancer in the pre-PSA era (comparing top to bottom quintile of intake, multivariate-adjusted HR = 1.78; 95% CI = 1.22-2.06; p_trend  = 0.003), but not in the PSA era (HR = 0.81; 95% CI = 0.56-1.17; p_trend  = 0.53), and the difference in associations was statistically significant (p for interaction = 0.02). Mayonnaise, a primary food source of ALA intake in our cohort, was likewise only significantly associated with lethal prostate cancer in the pre-PSA era. Among many other fatty acids that are correlated with ALA due to shared food sources, none was associated with lethal prostate cancer in the pre-PSA era. In conclusion, higher intake of ALA was associated with an increased risk of lethal prostate cancer in the pre-PSA era, but not in the PSA era. Potential reasons for the differential associations warrant further investigation.