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During the last four decades, there has been a rapid increase in the incidence of esophageal cancer of the adenocarcinoma type in the Western world, including in Sweden. The prognosis is poor as fewer than 20 percent of patients live 5 years after the diagnosis is established. These facts emphasize the value of preventive measures and early detection in reducing death from esophageal cancer. There is a great need to better understand the causes of this cancer and to develop tailored prevention strategies as well as to detect this cancer at a curable stage in individuals at greatly increased risk of esophageal cancer. First, we intend to perform a study using a particularly interesting and valuable analysis method (Mendelian randomization analysis) to test the hypothesis that heritable levels of metabolic and inflammatory biomarkers in the body influence the risk of esophageal cancer and its pre-stage by using pooled data from large and well-designed studies from different parts of the world. In the second study, we plan an analysis of metabolic and inflammatory biomarkers in the blood that can predict the risk of esophageal cancer as well as develop models that identify individuals at particularly high risk of this cancer. The project intends to increase knowledge about the causes of esophageal cancer and to find ways to preventive measures as well as opportunities to detect esophageal cancer at an earlier stage where it can be cured. If metabolic and inflammatory changes are of great importance for the development of esophageal cancer, it may also provide new opportunities for new treatments in the future. Knowledge of substances in the blood that can predict cancer risk can help identify people at high risk for esophageal cancer who would benefit from preventive measures. All the studies together can help reduce the number of deaths from this cancer in the future.

During the last four decades, there has been a rapid increase in the incidence of esophageal cancer (of the adenocarcinoma type) in the western world, so also in Sweden. The forecast is comparatively poor. Less than 20 percent of patients live 5 years after the diagnosis is established. Esophageal cancer is characterized by a striking male dominance (up to 9 men on 1 woman). The underlying causes of this are unknown, but sex-hormonal effects are highly probable, although not proven. This area is of great interest because it can provide suggestions for new prevention and treatment of this growing and aggressive form of cancer. First, we will examine the relationship between how different levels of circulating sex hormone levels affect the risk of esophageal cancer in a large case-control study in Norway where blood samples were taken before contracting esophageal cancer. Second, using pooled data from 14 large and well-designed studies, we propose a study that uses a particularly interesting assay (Mendelian randomization assay) to test the hypothesis that hereditary levels of sex hormones in the body affect the risk of esophageal cancer and Barrett's esophagus. Through this project, we can hopefully find reasons for the extreme male dominance, which can lead to pioneering new insights into the emergence of esophageal cancer. If we can prove that the female sex hormone estrogen has a protective effect or that the male sex hormone testosterone carries an increased risk of esophageal cancer, this would lead to very interesting research on new hormonal treatment to prevent esophageal cancer in high-risk individuals and as adjunctive treatment for esophageal cancer. All of these research efforts can enable new strategies for the prevention and treatment of esophageal cancer.

During the last four decades, there has been a rapid increase in the incidence of esophageal cancer (of the adenocarcinoma type) in the western world, so also in Sweden. The forecast is comparatively poor. Less than 20 percent of patients live 5 years after the diagnosis is established. Esophageal cancer is characterized by a striking male dominance (up to 9 men on 1 woman). The underlying causes of this are unknown, but sex-hormonal effects are highly probable, although not proven. This area is of great interest because it can provide suggestions for new prevention and treatment of this growing and aggressive form of cancer. First, we will examine the relationship between how different levels of circulating sex hormone levels affect the risk of esophageal cancer in a large case-control study in Norway where blood samples were taken before contracting esophageal cancer. Second, using pooled data from 14 large and well-designed studies, we propose a study that uses a particularly interesting assay (Mendelian randomization assay) to test the hypothesis that hereditary levels of sex hormones in the body affect the risk of esophageal cancer and Barrett's esophagus. Through this project, we can hopefully find reasons for the extreme male dominance, which can lead to pioneering new insights into the emergence of esophageal cancer. If we can prove that the female sex hormone estrogen has a protective effect or that the male sex hormone testosterone carries an increased risk of esophageal cancer, this would lead to very interesting research on new hormonal treatment to prevent esophageal cancer in high-risk individuals and as adjunctive treatment for esophageal cancer. All of these research efforts can enable new strategies for the prevention and treatment of esophageal cancer.