Use of biomarkers in epidemiology. The example of metabolic susceptibility to cancer.
This paper examines the methodological problems faced in epidemiological studies which use a particular class of biomarkers, those of genetic susceptibility to cancer. Their use in epidemiology is increasing, they raise special methodological questions and entail particular ethical consequences. A list of questions concerning the validity of the studies is discussed. (1) Is the test used to measure the genotype valid, i.e. sensitive and specific? (2) Is there a discrepancy between the genotype and its phenotypic expression? (3) If so, what conditions are deemed to be responsible for such discrepancy (for example, metabolic impairment due to cancer)? (4) Is there clear evidence that one phenotype is associated with an increased risk of cancer? (5) Is a specific chemical exposure known to be a cause of the cancer at issue and metabolized by the polymorphic enzyme? (6) Can any confounding exposure, i.e. some exposure which is associated with the phenotypic expression (for example by inducing the enzyme activity) and also with cancer risk, be identified? (7) Can any kind of selection bias, i.e. selective inclusion of subjects in the study, conditional to their metabolic status, be identified? (8) Are the results of the studies consistent and internally coherent? For example, does the association appear with all histologic types of cancer at a certain site? If not, is there any convincing explanation for the discrepancies?
Vineis
P
P
Unit of Cancer Epidemiology, Main Hospital, Torino, Italy.
D015415:Biomarkers / Q000737:chemistry*; D019389:Cytochrome P-450 CYP2D6; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D003647:Debrisoquin / Q000032:analysis* / Q000378:metabolism*; D004198:Disease Susceptibility / Q000453:epidemiology*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007527:Isoenzymes / Q000032:analysis; D006899:Mixed Function Oxygenases / Q000032:analysis; D009369:Neoplasms / Q000453:epidemiology* / Q000235:genetics; D010641:Phenotype
D015415:Biomarkers; D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D019389:Cytochrome P-450 CYP2D6; D003647:Debrisoquin