Technical Abstract: Pancreatic cancer is a rapidly fatal disease and little is known about its etiology. Epidemiological studies have suggested that cooking methods may affect the risk of pancreatic cancer. Dietary carcinogen heterocyclic aromatic amines (HCA) are generated during high temperature cooking of animal meat and have been shown to induce pancreatic tumor in experimental animals. It is unknown whether exposure to HCA contributes to the development of pancreatic cancer among individuals with a high consumption of animal meat. In a hospital-based case-control study, we have assessed the dietary intake of several HCA compounds using a validated dietary questionnaire. Cases were patients with newly diagnosed and pathologically confirmed adenocarcinoma. Controls were non-blood relatives and friends of patients who are treated for various types of cancer at UT M.D. Anderson Cancer Center. Cases and controls were frequency matched for race, sex and age (±5 years). Initial analysis of data from 147 cases and 144 controls have shown that the average intake (g/day) of red meat and white meat was comparable between cases and controls, but a greater portion of the cases than that of the controls consumed well-done meat. Our data showed that the median level of PhIP, MeIQx, and DiMeIQx among controls was 99.8, 32.5, and 1.7 ng/day respectively, which were comparable to previously reported values in studies conducted among U.S. populations. HCA values were categorized by using the 75th percentile of the HCA values among controls as cut-off points Logistic regression analysis was performed and we estimated that the age-, sex-, race-, and smoking-adjusted odd ratios (95% confidence interval) of pancreatic cancer were 2.2 (1.0-4.9) for PhIP, 1.9 (1.1-3.4) for MeIQx, 2.2 (1.2-3.8) for DiMeIQx, and 2.6 (1.2-5.9) for total HCAs (all P values were < 0.05). The same trend was observed when we use 90% percentile as a cutoff point. Moreover, when HCA intakes were introduced in the logistic model as continuous variables, a significant increase of risk was detected for each unit exposure of MeIQx (OR: 1.005, 95% CI: 1.001-1.009, P=0.014) and DiMeIQx (OR: 1.112, 95% CI: (1.035-1.195, P=0.004), and a borderline significantly increased risk was found for PhIP (OR: 1.001, 95% CI: 1.000-1.002, P=0.065). The intake level of the three HCA compounds was significantly correlated with each other (correlation coefficient ranged from 0.54 to 0.88, P<0.01). These data support the hypothesis that dietary HCA exposure increases the risk of pancreatic cancer.