Scientific Concept of the National Cohort (status ... - Nationale Kohorte

A.2
A.2. Scientific background and rationale for study elements
The identification of biomarkers that quantify metabolically active adipose tissue beyond
anthropometric parameters represents a complementary approach to define an ”obesity
phenotype” that is relevant for chronic disease risk 251 , and this approach can also provide
essential insight into physiologic mechanisms of disease development. In addition, metabolically
determined markers of chronic disease risks can constitute an important component
in prediction models for chronic disease risks and may also represent direct targets for
intervention through means of diet, lifestyle, or drug treatment. Results from prior studies
suggest that there may be a substantial overlap in metabolic pathways leading to diabetes,
CVD, various cancers, neurodegenerative diseases, and early death.
Assessment of metabolic parameters:
Level 3: Analyses of biomaterials
A.2.4.2 diet
Since prospective cohort investigations into the causes on chronic disease were started up,
as early as in the 1970s, diet has been a central focus of interest, and from the 1980s, many
large-scale prospective studies were initiated worldwide to address relationships of diet with
cancer, CVD, diabetes, and overall mortality 254, 255 . In these larger studies, habitual dietary
intake was generally assessed using food frequency-type questionnaires, in some cohorts
(e.g., the EPIC cohort) combined with 24-h diet recalls in calibration substudies.
Comprehensive summaries of this research by international expert panels, such as that
of the World Cancer Research Fund, showed conclusive evidence for increased risks of
certain cancer types in association with higher reported consumption levels of alcohol, red
meat, and processed meats, and a possible reduction in certain cancer risks at high intake
levels of dietary fiber and whole-grain foods, although generally the associations with risk
were of a relatively modest magnitude. For CVD, prospective studies and intervention trials
have shown reduced risks in relation to higher consumption levels of fruits, vegetables,
and n-3 polyunsaturated fatty acids 256-258 , and increased risks in relation to consumption of
saturated fatty acids and trans-fatty acids relative to monounsaturated and polyunsaturated
fatty acids and red meat. Surprisingly, only a few studies reported specifically about the role
of diet for heart failure, atrial fibrillation, and subclinical arteriosclerosis.
In spite of several consistent findings relating diet to risks of cancer and CVD, evidence has
also been increasing that there are limits to the validity of dietary intake assessments based
on food frequency questionnaires. For example, case-control studies nested within the
European Prospective Investigation into Cancer and Nutrition (EPIC) cohort have shown
clear inverse relationships of serum vitamin C with gastric cancer risk 259 or several serum
B vitamins with cancers of the lung and colorectum 260, 261 , and serum lycopene with risk of
prostate cancer 262 , where parallel evaluations on nutrient intake estimates calculated from
questionnaires did not. Furthermore, in one of the regional subcohorts of EPIC, in Norfolk
(UK), increased breast cancer risk was observed in association with higher intakes of dietary
saturated fats as assessed by replicate, weighed food records, but not with dietary fat
assessments by food frequency questionnaires, and a similar contrast was observed more
recently in the US Women’s Health Initiative cohort 263-265 . This indicates that measurement
error included in data derived from food frequency questionnaires may obscure existing
diet–disease association, even associations of substantial magnitude. In-depth dietary validation
studies that used recovery-based biomarkers for total dietary energy and protein as
reference measurements were more valid for 24-h diet recalls than for food frequency questionnaires
239, 266 . Thus, increasing precision of dietary assessment in the National Cohort is
mandatory; this aim will be achieved through a combination of repeated 24-h recalls, a short
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