title: PASSCLAIM--diet-related cancer.
abstract: BACKGROUND
  The role of dietary factors in the aetiology of human cancer is an area, which has attracted intense interest in recent years. The suggestion that approximately one third of all cancers may be caused by an 'inappropriate' balance of food components has led to the attractive contention that we can significantly decrease cancer incidence through dietary recommendations and a change in dietary habits in populations. Thus, a key issue must be to establish clear criteria, which must be met in order to be able to make 'cancer risk reduction' claims for food components. In this area, the one true marker is the malignant human tumour, which for practical reasons is usually not accessible to claims. In its absence, we must rely on alternative markers--biomarkers/surrogate endpoints. This paper mainly deals with the link of these biomarkers to the endpoint tumour and their usefulness for making claims. Some claims have been made based on epidemiological studies.
  
  
  OBJECTIVE
  Can we identify targets/ biomarkers in the chain of events from initial 'exposure' to overt malignant tumour, whose modification can be used to make 'anticancer' claims for food components?
  
  
  RESULTS
  We identified 18 targets/markers in the above chain of events whose modification 'have the potential' to be used for 'reduction of cancer risk' claims for food components. These targets/markers fall under 5 broad headings: tumours and preneoplastic changes; cellular targets/markers; gut luminal markers; angiogenesis and metastasis; carcinogen metabolising enzymes; genetic events.
  
  
  CONCLUSIONS
  The strongest markers presently available are precancerous lesions (e. g. polyps or aberrant crypt foci) in humans and precancerous lesions and tumours in animal models. The only marker that presently can be used for a 'reduction of disease risk' claim (type B) for food components is 'polyp recurrence'. Type B claims cannot be made on the basis of results in animal models. All of the other biomarkers examined presently lack validation against the 'true endpoint', the tumour, and thus cannot be used for type B claims. 'Reduction of disease risk' claims in the area of 'diet-related cancer' should be based primarily on human intervention studies using relevant/acceptable endpoints. An important area for future research will be the validation of these surrogate endpoints.
authors.affiliation: Department of Medical Nutrition, Karolinska Institute, Novum, S-14186, Huddinge, Sweden.
authors.forename: Joseph
authors.initials: J
authors.lastname: Rafter
authors.forename: Mirjam
authors.initials: M
authors.lastname: Govers
authors.forename: Paule
authors.initials: P
authors.lastname: Martel
authors.forename: Daphne
authors.initials: D
authors.lastname: Pannemans
authors.forename: Beatrice
authors.initials: B
authors.lastname: Pool-Zobel
authors.forename: Gerhard
authors.initials: G
authors.lastname: Rechkemmer
authors.forename: Ian
authors.initials: I
authors.lastname: Rowland
authors.forename: Sandra
authors.initials: S
authors.lastname: Tuijtelaars
authors.forename: Jan
authors.initials: J
authors.lastname: van Loo
mesh_terms: D000818:Animals; D017209:Apoptosis; D001419:Bacteria / Q000201:enzymology; D014408:Biomarkers, Tumor; D002273:Carcinogens; D003110:Colonic Neoplasms; D003111:Colonic Polyps; D051546:Cyclooxygenase 2; D004249:DNA Damage; D004260:DNA Repair; D004032:Diet; D005243:Feces; D058870:Food, Organic; D006293:Health Promotion; D006801:Humans; D008565:Membrane Proteins; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000209:etiology* / Q000235:genetics; D009389:Neovascularization, Pathologic; D011230:Precancerous Conditions; D011451:Prostaglandin-Endoperoxide Synthases
chemical_list: D014408:Biomarkers, Tumor; D002273:Carcinogens; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases