There is ample evidence from basic research and animal carcinogenicity studies that heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) are mutagens and carcinogens. However, there was a paucity of human data due to a lack of appropriate investigative tools. We developed the first validated cooked meat module within a food frequency questionnaire (FFQ) in the United States of America and created databases to be used in conjunction with this FFQ to estimate intake of HCAs and benzo[a]pyrene, a marker of PAHs. It became clear that other aspects of meat may also contribute to carcinogenesis; in particular, we are pursuing two additional areas: processed meat and iron exposure in relation to cancer risk. To investigate these hypotheses, we have expanded the cooked meat module to include detailed information on processed meats and fish. In addition, we are developing two databases, one for total iron and heme iron in cooked meat and the other for nitrite, nitrate, and N-nitroso compounds in processed meats. In this report, we will outline the methods used to develop the meat questionnaires, the databases, a software package for generating the intake values, and the methods used to generate nutritional data from nationally representative samples.

Epidemiologic studies have evaluated the risk of breast cancer related to dietary fat intake, but only recently have other dietary factors received attention. Frequent intakes of fruit, vegetables and fiber have been associated with low risk of the disease in some studies but results are inconsistent. In a large case-control study of early-onset breast cancer, we evaluated risk related to a variety of food groups, associated micronutrients and non-nutritive constituents. Cases treated with chemotherapy appeared to have altered reporting of food intake and were excluded. Analyses were restricted to 568 cases with in situ and localized disease and 1,451 population-based controls. Reduced risks were observed for high intake of cereals and grains [odds ratio (OR) ‫؍‬ 0.84, 95% confidence interval (CI) ‫؍‬ 0.6-1.1 for highest compared with lowest quartile], vegetables (OR ‫؍‬ 0.86, 95% CI ‫؍‬ 0.6-1.1), beans (OR ‫؍‬ 0.87, 95% CI ‫؍‬ 0.7-1.2) and fiber from beans (OR ‫؍‬ 0.88, 95% CI ‫؍‬ 0.7-1.2). However, no trends of decreasing risk across quartiles of increasing intake were observed. Risk was not associated with dietary constituents related to these food groups including dietary fiber, carotenoids, vitamins A, C and E and folate. Incorporation of information from vitamin supplements did not alter the results for micronutrients. Our data suggest that intakes of cereals and grains, vegetables and beans are associated with minimal, if any, reduction in risk of early-stage breast cancer among young women.

The nutrient and heterocyclic amine (HCA) intake of 165 healthy participants was assessed using a self-administered food frequency questionnaire (FFQ), which included a meatcooking practices module. A database containing the HCA IntroductionNumerous studies have demonstrated an association between red meat intake and the etiology of various cancers (1-8). A group of mutagenic and carcinogenic compounds called heterocyclic amines (HCAs), formed through pyrolysis of amino acids and creatine in meat using high temperature cooking techniques (9), have been implicated in this association. HCAs are among the most potent mutagens tested by the Ames Salmonella test (10) and have demonstrated their carcinogenicity in animals producing tumors in a variety of organs (11,12). Assessment of dietary HCA intake is challenging as the HCA composition of meat varies according to cooking technique, temperature, cooking time, and meat type (13-16). Epidemiological studies have tried to overcome these difficulties using surrogate markers of HCA intake such as the method of cooking, surface browning, total cooking time, and gravy intake (1, 17, 18). These studies produced suggestive but inconsistent links between HCA intake and cancer risk. Therefore, to investigate the role of HCAs in cancer etiology, improvements in the assessment of HCA intake are required. This study describes the development and validation of a meat-cooking practices module, which was included in a food frequency questionnaire (FFQ), to assess dietary HCA intake with greater accuracy. A database of the HCA content of commonly consumed meats, subjected to representative cooking practices, was developed and used in conjunction with this meat-cooking practices module. The aim of the present study therefore was to assess the relative validity of the newly developed meatcooking practices module and to assess the absolute dietary HCA intake in a healthy population. Dietary intake of the two most abundant HCAs was considered: 2-amino-3,8-dimethylimadazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenyl-imidazo [4,5-b]pyridine (PhIP).

Large epidemiological studies often require short food frequency questionnaires (FFQ) to minimize the respondent burden or to control for confounding from dietary factors. In this analysis, we compared the extensively used National Cancer Institute-Block 60- and 100-item FFQs with one another and with usual intake as estimated from 12 days of validation data. The analysis focused on nutrients from different aspects of the diet, including energy, fat, saturated fat, beta-carotene, dietary fiber, and vitamin C. By use of an errors-in-variables analysis, the correlations of usual intake with the two types of FFQs for these nutrients were not different. Attenuation coefficients, a measure of misclassification error, for both FFQs were of similar magnitude and indicated that substantial attenuation of logistic regression coefficients would result from either FFQ. Our results confirm previous analyses describing the validity and utility of the 60-item FFQ (Epidemiology 1, 58-64, 1990) and indicate that it is essentially equivalent to the 100-item FFQ for epidemiological analyses of major nutrients.

These data suggest a modest relationship between intakes of sweet items with risk of in-situ and localized breast cancer in young women. This relation is consistent with the hypothesized link of high insulin exposure and risk of breast cancer. There was some suggestion that women who ate many times during the day were at reduced risk of disease, which is also consistent with an insulin-related mechanism.