Influence of observational study design on the interpretation of cancer risk reduction by carotenoids

Recently published literature has been reviewed to determine whether lycopene, beta-carotene, alpha-carotene, and beta-cryptoxanthin are associated with reductions in cancer risk and whether study findings differ by study design. A total of 57 publications meeting pre-defined inclusion and exclusion criteria were identified, with the majority (55) being observational studies. None of the intervention studies supported a significant reduction in cancer risk with carotenoid (beta-carotene) supplementation. The majority of observational studies did not support significant reductions in cancer risk with increased carotenoid dietary intakes/circulating levels. A larger percentage of case-control studies supported significant associations between increased dietary intakes/circulating levels of carotenoids relative to prospective (cohort and nested case-control) studies. Compared to prospective studies, case-control studies cannot be used to establish temporality and may be more susceptible to selection and recall biases. Thus, diet-disease relationships suggested by case-control studies should ideally be confirmed by additional evidence from prospective studies.