Whereas the relevance of particular markers for the diagnosis or prognosis of specific diseases may be well established, their relevance in a general population is typically less clear as very few prognostic studies have carefully assessed the predictive value of these markers for maintenance of health.
The classification of germ-cell testicular cancer into seminoma and non-seminoma has a well established prognostic relevance.
The elucidation of the factors involved in the signal transduction pathway of preconditioning has been the subject of intense investigation and although the participation of factors such as PKC [ 17, 19, 27] and mitoKATP channels [ 16- 21] is well established, their relevance and the sequence of activation remains controversial.
However, whereas the role of microsatellite instability and DNA mismatch repair gene defects in HNPCC is unquestionable and well established, the relevance of this phenomenon in GC is far from clear and currently has limited clinical value (Hayden et al. 1998).
Therefore the aim was to complement the proteomic data with a standard panel of well-known chemokines that are of established relevance in airway inflammation.
The inverse association between educational attainment and mortality is well established, but its relevance to vascular events and renal progression in a population with chronic kidney disease (CKD) is less clear.
Although redox modification of RyR activity is well established, its physiological relevance and role in relation to endogenously generated oxidants remains incompletely understood.
Although the pharmacological utility of the bacterial macrolides FK506 and rapamycin is well established, the physiological relevance of their interactions is less clear.
While the role of different pro-survival Bcl-2 proteins appears well established, information on the relevance of their antagonists, the proteins of the BH3-only subgroup of the Bcl-2 family, including Bim, Bid, Puma and Bmf, is currently lacking.
In regard to the first two parameters, although KRAS mutation status is, in fact, a negative marker predicting for resistance, its biological relevance seems well established: about 30 40% of CRC carry mutations in this gene occurring early in colorectal carcinogenesis [17], [18], [19].
IQ scores are of particular interest because their clinical relevance is well established, with moderate correlations (r ~ 0.50) between school-age IQ and adult occupational status (Jencks et al. 1972; McCall 1977).
