Inherent difficulties in epidemiological studies involving phenotyping.
Phenotyping studies on a possible association between genetic polymorphisms and cancer raise specific problems that are mostly related to accurate determination of enzymatic activity in individuals. These difficulties are addressed on the basis of investigations into the relationship between the CYP2D6 phenotype and lung cancer. Only the problems concerning the design and analysis of epidemiological studies and which are specifically related to the genetic polymorphism are discussed. In particular, factors likely to modify enzymatic activity are potential sources of error when assessing the relationship between cancer and genetic polymorphism. These factors are mainly related to the study population (ethnicity, co-administered drugs, underlying diseases, etc.) or to the phenotyping protocol (probe drugs, urine collection, techniques). These aspects of phenotyping-related difficulties are the key issues in the design of phenotyping studies.
Benhamou
S
S
INSERM U521, Unit of Cancer Epidemiology, Institut Gustave-Roussy, Villejuif, France.
Bouchardy
C
C
Jacqz-Aigrain
E
E
D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D004812:Epidemiologic Methods; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*
D019389:Cytochrome P-450 CYP2D6