Dietary phytoestrogens and esophageal cancer

Sammanfattning: Esophageal cancer is the eighth most common invasive cancer in the world, a cancer with an increasing incidence and male predominance, and there is a great need for potential dietary prevention. The overall aim of this thesis was to evaluate whether the dietary phytoestrogens lignans might play a protective role in the etiology of esophageal cancer, including gastroesophageal junctional adenocarcinoma. In Paper I, we examined the association between intake of dietary lignans based on a 63-item food frequency questionnaire (FFQ) and risk of esophageal cancer in a Swedish nationwide population-based case-control study conducted in 1995-1997. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Participants in the highest quartile of lignan intake compared with the lowest quartile showed a decreased risk of esophageal adenocarcinoma (OR=0.65; 95% CI: 0.38-1.12) and gastroesophageal junctional adenocarcinoma (OR=0.37; 95% CI: 0.23-0.58), while no clear associations were found for esophageal squamous-cell carcinoma. In Paper II, we validated the use of two FFQs (the 67-item FFQ-87 and the 93-item FFQ-97) for the assessment of dietary lignans compared to the serum biomarker enterolactone, the main metabolite of dietary lignans in the human body. Based on the FFQ-97, the correlation between lignan intake and serum enterolactone was significant, but the value of the correlation coefficient was small (r=0.22, p=0.01). No significant correlation was observed for the FFQ-87. In Paper III, we further evaluated the possible association between lignan intake based on the FFQ-97 and risk of esophageal and gastric adenocarcinoma using a prospective study design. Among 81,670 participants who were followed up during 1998-2009, hazard ratios (HRs) and 95% CIs were calculated. No statistically significantly decreased risk was found. Compared with the lowest quartile of lignan intake, the adjusted HRs of the highest quartile were 0.96 (95% CI: 0.46-2.00) for esophageal and gastroesophageal junctional adenocarcinoma, and 0.89 (95% CI: 0.52-1.55) for gastric adenocarcinoma. In Paper IV, we defined a dietary pattern characterized by dietary intake of lignans, quercetin and resveratrol, the three common phytochemicals with estrogenic properties, in a Swedish population-based case-control study. A decreased risk of esophageal cancer was found among individuals with a high dietary intake of these three phytochemicals. Comparing the highest quintile of food pattern score with the lowest quintile, the adjusted ORs were 0.24 (95% CI: 0.12-0.49) for esophageal adenocarcinoma, 0.31 (95% CI: 0.15-0.65) for esophageal squamous-cell carcinoma, and 0.49 (95% CI: 0.28-0.84) for gastroesophageal junctional adenocarcinoma. In conclusion, a high dietary intake of phytoestrogens, typically lignans, might decrease the risk of adenocarcinoma of esophagus and gastroesophageal junction. The FFQ-97 can be used to assess lignan exposure, and a dietary pattern characterized by a high dietary intake of lignans, quercetin, and resveratrol might prevent esophageal cancer.