Issues in the design and interpretation of studies of fatty acids and cancer in humans.

The methods used in nutritional epidemiology to study the relations between fatty acids and cancer risk include ecologic studies, case-control studies, cohort studies, and intervention trials examining either intermediate markers of cancer risk or cancer incidence. Each type of study design has its particular strengths and weaknesses. The inaccuracy of estimates of fatty acid intake from the use of dietary questionnaires linked to nutrient databases is a major limitation in nutritional epidemiology. Information on the concentrations of fatty acids in the circulation or in adipose tissue can complement estimations of dietary intake. Cancer prevention studies now underway are designed to test whole-diet effects on neoplasia and will not be able to separate the effects of specific fatty acids from those of other nutrients in the diet. The development of better intermediate markers of cancer risk could enable the use of experimental methods to assess the relation between specific fatty acids and cancer. Research findings as described in the literature are complicated both by the multiple hypotheses that can be tested when assessing fatty acid effects and by the uncertainties of multivariate adjustment. Although there are substantial obstacles to understanding the relations between fatty acid intakes and cancer risk, there is no better species than humans for inference about diet and cancer risk in people.