Biomarkers of dietary intake of flavonoids and phenolic acids for studying diet-cancer relationship in humans.
BACKGROUND
For many polyphenolic compounds found in plant-derived food, biological effects possibly relevant for cancer prevention have been shown. Since dietary intake estimates suffer from imprecision, the measurement of these compounds (or metabolites of) in biological specimens collected in epidemiological studies is expected to improve accuracy of exposure estimation.


OBJECTIVE
The current use of biomarkers in etiologic studies on polyphenolics and cancer risk is evaluated. In addition, available analytical methods are discussed with respect to the requirements for their integration in epidemiological studies, putting specific emphasis on the epidemiological validation of such markers.


METHODS
The scientific literature was screened for epidemiologic studies on the relationship of flavonoid and phenolic acid concentrations in human specimens (i.e. blood, urine) and cancer risk. In addition, original data on intra- and inter-subject variability of several flavonoids and phenolic acids are presented.


RESULTS
Although several techniques are used in bioavailability or short-term intervention studies, their integration in epidemiological studies is very limited. An exception are phytoestrogens where validated immunoassays allow the rapid measurement of large sample numbers with small sample volume. For several polyphenols, the data on the epidemiologic validity encourages for their use in epidemiological studies.


CONCLUSIONS
There are valid possibilities for additional biomarkers of flavonoid and phenolic acid intake that are best applied in prospective studies with more than one biological sample per subject. Currently, a combination of a single biomarker measurement with long-term dietary intake estimates will probably be the most valuable choice to decrease measurement error in exposure data.
Linseisen
Jakob
J
Unit of Nutritional Epidemiology, Division of Cancer Epidemiology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany. j.linseisen@dkfz.de
Rohrmann
Sabine
S
D001682:Biological Availability; D015415:Biomarkers / Q000097:blood / Q000652:urine; D005419:Flavonoids / Q000097:blood* / Q000493:pharmacokinetics / Q000652:urine*; D006801:Humans; D062385:Hydroxybenzoates / Q000097:blood* / Q000493:pharmacokinetics / Q000652:urine*; D009369:Neoplasms / Q000097:blood / Q000453:epidemiology / Q000517:prevention & control* / Q000652:urine; D009751:Nutritional Requirements; D009752:Nutritional Status; D054928:Validation Studies as Topic
D015415:Biomarkers; D005419:Flavonoids; D062385:Hydroxybenzoates; C017616:phenolic acid