Dietary phytoestrogens and esophageal cancer

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.

List of scientific papers

I. Lin Y, Yngve A, Lagergren J, Lu Y. Dietary intake of lignans and risk of adenocarcinoma of the esophagus and gastroesophageal junction. Cancer Causes Control. Jun 2012; 23(6):837-44.
https://doi.org/10.1007/s10552-012-9952-7

II. Lin Y, Wolk A, Håkansson N, Peñalvo JL, Lagergren J, Adlercreutz H, Lu Y. Validation of FFQ-based assessment of dietary lignans compared with serum enterolactone in Swedish women. British Journal of Nutrition. May 2013; 109(10):1873-80.
https://doi.org/10.1017/S000711451200387X

III. Lin Y, Wolk A, Hakansson N, Lagergren J, Lu Y. Dietary intake of lignans and risk of esophageal and gastric adenocarcinoma: a cohort study in Sweden. Cancer Epidemiology, Biomarkers & Prevention. Feb 2013; 22(2):308-12.
https://doi.org/10.1158/1055-9965.EPI-12-1138

IV. Lin Y, Yngve A, Lagergren J, Lu Y. A dietary pattern rich in lignans, quercetin and resveratrol decreases the risk of esophageal cancer. [Submitted]