The general objective of this thesis was to investigate associations between genetic variants involved in inflammation and epigenetics and age-related diseases in an elderly cohort to get more... Show moreThe general objective of this thesis was to investigate associations between genetic variants involved in inflammation and epigenetics and age-related diseases in an elderly cohort to get more insights in the patho-physiological mechanisms involved in age-related diseases, like cardiovascular disease, cognitive decline and cancer. For all analyses we used data of the participants of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). We have shown that subjects carrying genetic variants coding for a high pro-inflammatory profile or a low anti-inflammatory profile have an increased risk to develop cardiovascular disease and cognitive decline. Moreover, they tend to have an increased risk of dying as a consequence of cancer. Furthermore we have provided first evidence that the process of epigenetics can play an important role in the patho-physiology of age-related diseases. Future research is necessary to investigate how we can corporate these results into clinical practice. For example, Anti-inflammatory and immunosuppressive mechanisms may be attractive targets for disease prevention and/or treatment. Show less
Survival rates after surgical treatment of gastric, colon and rectal cancer can improve with preoperative and/or postoperative adjuvant treatment with chemo- and/or radiotherapy. The role of... Show moreSurvival rates after surgical treatment of gastric, colon and rectal cancer can improve with preoperative and/or postoperative adjuvant treatment with chemo- and/or radiotherapy. The role of epigenetic aberrancies such as DNA methylation is established to play a pivotal role in gastrointestinal carcinogenesis and malignant progression. This thesis describes novel epigenetic biomarkers that could tailor (neo)adjuvant treatment regimens to the patients who would benefit from them. The same markers could further be used to exclude those patients who would not gain more survival-years and would be unnecessarily exposed to the morbidity/mortality of additional chemo- and/or radiation therapy. Currently, nodal status is the single most important prognostic indicator in gastrointestinal cancers however this can only be reliably assessed by the pathologist after surgery. Currently, neoadjuvant regimens are more and more being studied and shown to be of benefit. This development necessitates biomarkers that are available before the operation. An important derived conclusion from this thesis is that the preoperative availability of primary tumor DNA methylation biomarkers holds great potential for tailoring neoadjuvant therapy. The thesis also describes technical advancements that will enable primary tumor DNA methylation assessment in small amounts of tissue as preoperative diagnostic tumor biopsies harvested during gastroscopy or colonoscopy Show less
