Role of dietary fat in the causation of breast cancer: point.

Introduction The question of whether or not a direct association exists between dietary fat and postmenopausal breast cancer risk has been the focus of numerous ecological, migrant, prospective cohort, case-control, and experimental studies conducted over the last several decades (1). No clear answer to this question, however, has yet been uncovered, and a considerable amount of controversy on the topic of dietary fat and breast cancer exists within the scientific community. When carrying out research studies in this area and interpreting their results, it is important to recognize that dietary fat is not a completely independent lifestyle risk factor. The effects of other lifestyle risk factors closely related to dietary fat—including caloric intake, weight gain, obesity, and physical activity—have a high probability of being intricately connected with the effects of dietary fat, per se. In fact, the expectation of separating the independent effects of these various factors on breast cancer risk may be unrealistic. Also, individual genetic susceptibilities may further cloud an existing dietary fat-breast cancer relationship. To illustrate, significantly increased breast cancer risk has been reported for postmenopausal women in the highest quartiles of exposure for total meat intake (a source of dietary fat) and for heterocyclic aromatic amines from cooked meats (2). Considering that polymorphisms in N-acetyltransferase 2—a xenobiotic metabolizing enzyme that influences detoxification rates of heterocyclic aromatic amines—determine whether postmenopausal women are slow acetylators or fast acetylators (3), measurement of the contribution to cancer risk by dietary fat from meat sources, particularly across studies, could readily be confounded by the acetylator status of the study population. Such differences in inherited genetic susceptibility, which result in environmental factors being a more important contributor to breast cancer in only some proportion of a study population, can limit the ability to detect associations because of misclassification of outcomes (4). Considering the integrated contributions to breast cancer risk stemming from individual genetic variations and the lifestyle factors noted above, there is little likelihood that epidemiological data alone can provide a definitive answer to what is undoubtedly a very complex relationship. In addition, methodological issues related to dietary assessment in epidemiological studies contribute further uncertainties to data interpretation. Although recognizing the limitations of an epidemiological approach to determining the true association between diet-related lifestyle factors and disease risk, epidemiological evidence, supported by consistent results from animal studies, has clearly suggested direct associations between breast cancer risk and total dietary fat, types of fat, obesity, weight gain, and physical activity.