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

A.2
A.2. Scientific background and rationale for study elements
pathway, type II) 71, 73 . Further important examples of tumor heterogeneity are endometrial
cancers, which exist in at least two major forms (“type I” and “type II”) 66, 67 , and lung cancers
65, 72 . For the cancers at each of these organ sites a growing body of evidence indicates
that different epidemiologic risk factors may exist for the different molecular subtypes 78-83 .
For prostate cancer, evidence showing that epidemiologic risk factors may vary strongly
between low-grade and high-grade tumors is also increasing 84 .
In addition to lung cancer, which is predominantly caused by smoking, a much higher incidence
is observed in Western Europe (including Germany) for most of the other “top twelve”
cancer types than in economically less developed parts of the world. This is the case, for
example, for cancers of the colon and rectum, pancreas, kidney (renal cell tumors), breast,
endometrium, ovary, and prostate. Migrant studies and studies of time trends of incidence in
Western Europe clearly indicate that environmental and lifestyle (nongenetic) factors must
be key determinants in the development of these and several other tumor types. Interestingly,
there are also strong international correlations of the incidence rates of these various
cancer types with those of type 2 diabetes, which have also been very much on the rise over
the last several decades, and CVD. The latter observations suggest that common environmental
and lifestyle factors may underlie various forms of chronic disease.
Established risk factors for different cancer types are manifold and range from reproductive
behavior, nutrition-related lifestyle factors, smoking and alcohol consumption, use of
hormonal medications, and chronic viral and bacterial infections and vary greatly by type
of tumor. Epidemiologic findings so far, however, have only partially identified the specific
lifestyle factors and other causes that explain the high risks of the aforementioned cancer
types. In the National Cohort, we plan to conduct extensive studies especially in the areas
of physical activity, excess body weight and metabolism, diet and nutrition, and chronic
infections and immune function, and we also plan to investigate the effects of intestinal
and oral microflora on tumor development. Account will be taken of other, established risk
factors such as use of exogenous hormones for contraception or postmenopausal replacement
therapy, use of other medications, family history of cancer, and smoking and alcohol
consumption. Furthermore, a point for special attention in the National Cohort is that of
socioeconomic and geographic variations in overall cancer risk, taking account of possible
differences in the use made of health care (e.g., screening participation) 85-88 .
There is increasing evidence that different molecular tumor subtypes may develop along
different etiological pathways and may be related to different risk factors. It is therefore of utmost
importance to collect detailed data on tumor stage, grade, histology, and molecular subtypes.
The first data source will be cancer registries; however, due to the rapidly moving field,
we will be able to provide additional morphologic and molecular subcharacterization of tumor
types by establishing a national, quality-assured bank of tumor samples (see Sect. A.3.5.5)
Assessment of cancer:
Examinations and questionnaires (at baseline and during reassessment)
Level 1: Questionnaire
Active follow-up (and medical verification of self-reports):
Self-report of physician-diagnosed tumors (in case of incomplete cancer registries)
Insofar as possible in combination with passive follow-up through: Cancer registries
Tumor tissue bank: Systematic collection of tumor materials for all incident cases of
cancer so as to allow further molecular and refined histopatologic characterization
of tumors.
A.2.2.4 Neurologic and psychiatric diseases
Many neurologic diseases are related to age. Thus, even with incidence remaining stable,
they will become more frequent in absolute numbers due to the increasing life expectancy.
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