Circulating markers of risk and etiology in colorectal cancer

• Main Author: Harbs, Justin
• Format: Doctoral or Postdoctoral Thesis
• Language: English
• Published: Umeå universitet, Onkologi 2023
• Subjects: Colorectal cancer; CRC; sex hormones; colon cancer; DNA methylation; proteomics; risk; etiology; Cancer and Oncology; Cancer och onkologi; Northern Sweden
• Online Access: http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-205431

Background: Colorectal cancer is the third most commonly diagnosed cancer in men and women. Worldwide around 2 million individuals are diagnosed each year – a number expected to increase as colorectal cancer risk factors become more prevalent. In men and women there is a difference in incidence, which possibly could be explained by inherent differences, including sex hormone profiles. The prognosis of colorectal cancer is highly dependent on the stage at diagnosis, with individuals diagnosed at early stages having the best long-term survival. However, as onset of symptoms can be diffuse, many individuals are diagnosed at later stages when survival rates are significantly poorer. Therefore, screening and prevention strategies to detect colorectal cancer at earlier stages or remove cancer precursors such as polyps may be key to increasing survival. Commonly used screening tools today include fecal blood tests and colonoscopy, but they have modest accuracy or may not be cost-effective. Being able to identify markers in blood, either for early detection, as a complementary or alternative screening method, or for risk stratification, could aid in solving this problem. Aim: The overall of aim of the thesis was to improve our understanding of underlying factors contributing to CRC etiology and to find biomarkers associated with CRC that could aid in the future development of effective risk prediction models. Methods: All studies included in this thesis were based on a case-control cohort nested within the Northern Sweden Health and Disease Study (NSHDS). Additionally in paper I, we also used data from the European Prospective Investigation into Cancer and Nutrition (EPIC), a large multi-center cohort study. In this paper we examined associations between sex hormones, sex hormone binding globulin (SHBG), and colon cancer in men. The study included 690 colon cancer cases and 690 matched controls. Paper II was a longitudinal study, using repeated samples from 80 men, on circulating sex hormones, SHBG, and DNA methylation ...