Investigation of causal associations between risk factors and cancer incidence (Doctoral thesis)

Παπαδημητρίου, Νικόλαος

he main goal of this thesis is the investigation of causal associations between risk factors and cancer incidence and it was achieved by following two approaches. Firstly, the burden of cancer was estimated as well as what part of it could be attributed to some established cancer risk factors. The second approach involved the investigation of nutritional epidemiology of cancer through the application of some modem techniques. First, a study was conducted in CHANCES consortium to calculate DALYs for cancer, overall and by cancer site and to estimate population-attributable fractions (PAFs) for selected cancer risk factors (smoking, adiposity, alcohol, physical inactivity, and type II diabetes) based on the calculated DALYs. In overall, 34,474 DALYs were lost out of which 82% were lost due to premature mortality. Lung cancer was responsible for the largest number of DALYs lost (22.9%), followed by colorectal cancer. Cigarettes smoking was the major risk factor responsible for the 24% of total burden. Secondly, an umbrella review of the evidence was conducted to systematically evaluate the robustness of the literature across diet, anthropometric measures and physical activity and the risk of cancer at different anatomical sites. Most strong associations were observed for breast and colorectal cancer. Obesity was the risk factor with the largest number of strong associations, followed by alcohol consumption while additional strong protective effects were observed for the consumption of wholegrain and dairy products and colorectal cancer risk. There were also cases several cases the evidence was more inconsistent, showing indication of bias and/or uncertainty. Moreover, a Nutrient - Wide Association Study (NWAS) was implemented to systematically and comprehensively evaluate the association between 92 foods or nutrients and risk of prostate cancer in EPIC cohort. After correcting for the multiple comparisons, no dietary factor retained a significant association. Additional analyses by subtype of prostate cancer revealed two significant associations. Intakes of dry cakes/biscuits and butter were associated with an increased risk of low-grade and aggressive prostate cancer respectively out of which the association for dry cakes/biscuits and risk of low-grade prostate cancer was replicated in NLCS. However, the results from the meta-analyses were significant in both cases. Lastly, a mendelian randomization study was conducted to investigate potential causal associations between genetically determined concentrations of 11 nutrients and risk of breast cancer using data from published GWAS studies. In overall, most dietary exposures didn’t show any associations with breast cancer except of magnesium that was positively associated with overall and ER positive breast cancer and phosphorus that was inversely associated with ER negative breast cancer.
Institution and School/Department of submitter: Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής
Subject classification: Carcinogens
Keywords: Φορτίο νοσηρότητας,Αιτιολογικά κλάσματα,Διατροφή,Παχυσαρκία,Φυσική άσκηση,Καρκίνος,Burden of disease,Attributable fractions,Diet,Obesity,Physical activity,Cancer
Appears in Collections:Διδακτορικές Διατριβές

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