Dietary fat and mammary carcinogenesis

Evidence that dietary fat has an influence on carcinogenesis comes from both epidemiological data and experiments with animals. The experimental studies have indicated that dietary fat acts primarily as a promoter of carcinogenesis and that the effect depends on the type as well as the amount of fat in the diet. Vegetable oils containing polyunsaturated fatty acids of the linoleic acid family (n-6) have been shown to enhance mammary tumorigenesis, but a fish oil containing polyunsaturated fatty acids of the linolenic acid family (n-3) had an inhibitory effect at higher levels of intake. These and other findings suggest that the effect may be related to prostaglandins or other biologically active products of polyunsaturated fatty acids. Epidemiological data show a positive correlation between dietary fat and mortality from cancer at various sites, and this is supported by results of animal experiments in the case of colon cancer and pancreatic cancer as well as breast cancer. In the epidemiological data, cancer mortality shows strong positive correlations with total dietary fat and with animal fat, but not with fat derived from plants. Fats and oils used as spreads, cooking fats, and salad oils are the main source of fat in the American diet. Other major sources are meats and dairy products. Fat intake could probably be reduced substantially without serious deleterious effects, and this might help to decrease the risk of developing certain types of cancer.     

Modification of mammary carcinogenesis and tissue peroxidation by selenium deficiency and dietary fat

This study investigates the interdependence of selenium and unsaturated fat intake as modifiers of 1. the incidence of mammary tumors induced by 7, 12‐dimethylbenz (a) anthracene; and 2. the lability of mammary tissue to lipid peroxidation. Results suggest that there is an association between susceptibility of the mammary gland to carcinogenesis and its lability to peroxidation, and that both parameters are intimately regulated by fat intake in conjunction with the selenium status of the animal.     

Dietary beta-carotene inhibits mammary carcinogenesis in rats depending on dietary alpha-linolenic acid content

To investigate whether dietary alpha-linolenic acid (ALA) content alters the effect of beta-carotene on mammary carcinogenesis, we conducted a chemically induced mammary tumorigenesis experiment in rats randomly assigned to four nutritional groups (15 rats per group) varying in beta-carotene supplementation and ALA content. Two oil formula-enriched diets (15 %) were used: one with 6 g ALA/kg diet in an essential fatty acids (EFA) ratio of linoleic acid:ALA of 5:1 w/w (EFA 5 diet), the other with 24 g ALA/kg diet in an EFA ratio of 1:1 w/w (EFA 1 diet), both designed with a similar linoleic acid content. beta-Carotene was either added (10 mg/kg diet per d) or not added to these diets. beta-Carotene supplementation led to decreased tumour incidence and tumour growth when added to the EFA 5 diet, whereas it had no effect when added to the EFA 1 diet. The decreased tumour growth did not result from an involvement of lipoperoxidation (tumour malondialdehyde content being similar between the groups) or from an inhibition of tumour cell proliferation (as there was an unchanged S phase fraction in the tumours). We concluded that an adequate content of ALA in the diet is required to allow a protective effect of beta-carotene in mammary carcinogenesis. Whether such an interaction between ALA and beta-carotene influences the risk of breast cancer in women needs to be investigated.     

Effect of energy intake on the promotion of mammary carcinogenesis by dietary fat

The effect of low-fat and high-fat diets on the induction of mammary carcinomas by 1-methyl-1-nitrosourea (MNU) was studied in female Sprague-Dawley rats. All rats were given MNU (25 mg/kg body wt) at 50 days of age. For the first 17 weeks after carcinogen administration, they were fed a purified diet containing either 5 or 20% fat incorporated into agar gel. Food intake was restricted, so that the amounts fed provided the same amount of net utilizable energy each day for both groups, regardless of the fat content of the diets. From 17 to 32 weeks, the diets were fed ad libitum. During the restricted feeding period, there was no significant difference in tumor incidence or in the number of tumors detected between the groups. During the weeks in which animals were fed ad libitum, significantly more tumors appeared in the high-fat group than in the low-fat group. The data provide support for the hypothesis that consumption of a high-fat diet can lead to an enhancement of mammary carcinogenesis. It appears, however, that diets must be consumed ad libitum for the stimulatory effect on tumor occurrence to be exhibited.     

Effect of energy intake on the promotion of mammary carcinogenesis by dietary fat

The effect of low‐fat and high‐fat diets on the induction of mammary carcinomas by 1‐methyl‐1‐nitrosourea (MNU) was studied in female Sprague‐Dawley rats. All rats were given MNU (25 mg/kg body wt) at 50 days of age. For the first 17 weeks after carcinogen administration, they were fed a purified diet containing either 5 or 20% fat incorporated into agar gel. Food intake was restricted, so that the amounts fed provided the same amount of net utilizable energy each day for both groups, regardless of the fat content of the diets. From 17 to 32 weeks, the diets were fed ad libitum. During the restricted feeding period, there was no significant difference in tumor incidence or in the number Of tumors detected between the groups. During the weeks in which animals were fed ad libitum, significantly more tumors appeared in the high‐fat group than in the low‐fat group. The data provide support for the hypothesis that consumption of a high‐fat diet can lead to an enhancement of mammary carcinogenesis. It appears, however, that diets must be consumed ad libitum for the stimulatory effect on tumor occurrence to be exhibited.     

Dietary fat

For the past two decades, epidemiologists have observed lower risks of lung, breast, prostate, colon, and other cancers in populations that frequently consume fruits and vegetables. Numerous phytoestrogens have been shown to be anticarcinogenic under experimental conditions and may account for at least part of the cancer‐prevention effects of fruit and vegetable consumption. These plant constituents include isoflavonoids, coumestans, lignans, phytosterols, and flavonoids. DietSys, the nutrient analysis program associated with the National Cancer Institute Health Habits and History Questionnaire (HHHQ), and other nationally available nutrient analysis databases do not fully assess these constituents. Therefore, we modified DietSys to include these components in foods on the basis of published values. In addition, as part of an epidemiological study of prostate cancer, we modified the food‐frequency component of the HHHQ to include the main foods contributing to phytoestrogen intake. Although there are limitations to the consistency and quality of many of the values because they were gathered from a variety of sources, our approach should provide a useful first tool for assessing the epidemiological association between phytoestrogen consumption and cancer risk. Furthermore, this work has already facilitated the identification of the major dietary contributors with phytoestrogen activity and prioritized future laboratory analyses of specific foods toward the development of a more complete and accurate database.     

Dietary docosahexaenoic acid suppresses N-methyl-N-nitrosourea-induced mammary carcinogenesis in rats more effectively than eicosapentaenoic acid

We compared the effects of identical amounts but different proportions of dietary n-3 polyunsaturated fatty acids (PUFAs) on N-methyl-N-nitrosourea (MNU)-induced mammary cancer in a rat model. The ability of dietary docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) to suppress mammary cancer was evaluated. Female Sprague-Dawley rats were randomly assigned to three groups and maintained on diets containing 10% fatty acid consisting of EPA, a 1:1 mixture of EPA-plus-DHA, or DHA. The experimental diet was started after administration of MNU at 49 days of age, and the rats were maintained on the respective diets until the largest mammary tumor reached >1 cm in diameter or until the end of the study period (20 wk after MNU). All histologically detected mammary carcinomas were evaluated, irrespective of size. The DHA diet was associated with significant suppression of the carcinogenic effect of MNU compared with the EPA and EPA-plus-DHA diets: tumor incidence decreased to 23% (3/13) compared with 73% (11/15) and 65% (12/17) (P < 0.01 and P < 0.05, respectively); tumor multiplicity decreased to 0.23 compared with 1.67 and 1.59 (P < 0.01 and P < 0.05, respectively). There was no significant difference in tumor latency among the DHA, EPA, and EPA-plus-DHA groups (119, 105, and 117 days, respectively). Over 20 wk, the fatty acid composition of serum and mammary fat tissue reflected differences in the dietary n-3 PUFAs. Although DHA suppressed MNU-induced mammary carcinogenesis more effectively than EPA, generalized steatosis including mammary fat tissue appeared in all three groups.     

Dietary fat and physical performance

Although the relationship between dietary carbohydrate and physical performance is well described, there is much controversy about the relationship between dietary fat and physical performance. Recently, several studies have tried to clarify this relationship. Here the effects of acute fat on metabolism and performance will be discussed, as well as the effects of short-term and long-term high-fat diets.     

Dietary fat and tumor metastasis

Evidence from several types of studies indicates a relationship between fat intake and occurrence of malignant tumors at specific sites. When rodents are fed high-fat diets, the incidence of mammary tumors sharply increases and latency of tumor appearance is greatly diminished, as compared with the same parameters in animals fed low levels of fat. Despite advances in surgical technique and the development of aggressive therapies for the treatment of primary cancers, most deaths in humans with cancer are caused by metastasis. Accordingly, we have reviewed the process of metastasis and have focused on the question of whether dietary fat can play a role. Metastasis is a complex, multistep, progressive process, and dietary fats may affect specific events such as implantation, survival, and proliferation of tumors. Finally, we discuss possible mechanisms by which dietary fat can modulate metastasis. Available data lead us to stress the importance of assessment of metastasis in studies of the effects of dietary fat on tumorigenesis.     

Dietary fat and natural-killer-cell activity

An intervention trial designed to lower the amount of fat in the diet was conducted to test the effect of reduced fat consumption (LF diet) on activity of natural killer (NK) cells in humans. Of 26 men enrolled initially, 17 successfully completed the intervention and lowered their fat intake to less than 30% of calories as fat. Data were analyzed in two ways. The paired t test showed a marked increase in NK-cell activity from baseline to the end of the LF-diet intervention (t = 4.77, p = 0.0002). Results of a general linear model showed an effect of lowering total dietary fat on increased NK-cell activity (approximately 0.53% increase for each absolute percent of calories as fat, p = 0.14) for all men and a highly significant effect in a subset of men who ate greater than 25% of calories as fat at baseline (approximately 1.22% increase, p = 0.009). These results were obtained after changes in total caloric intake, weight, exercise, and other fat-related covariates were accounted for.     

Ethanol consumption and DMBA-induced mammary carcinogenesis in rats

In this study, we report that chronic ethanol intake at 20% of calories can enhance the initiation stage and at 15% of calories can enhance the promotion stage of 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumorigenesis in female Sprague-Dawley rats. Ethanol consumption at 20% of calories by female rats from 25 to 53 days of age was associated with a significant increase in terminal end bud (TEB) structures and a significant decrease in alveolar bud structures of the normal mammary gland. In addition to changes in mammary gland morphology, ethanol consumption at 20% of calories also was associated with a significant increase in incorporation of [3H]thymidine into mammary DNA and a significant increase in the DNA-labeling index of mammary TEB. Therefore, specific ethanol intakes can enhance DMBA-induced mammary tumorigenesis. The enhancement of the initiation stage partly may be explained by alterations in the structural development of the normal rat mammary gland that increase susceptibility to chemically induced mammary tumorigenesis.     

Dietary behaviors associated with total fat and saturated fat intake

OBJECTIVE: To estimate percentages of US adults who have adopted behaviors promoted by dietary guidance about how to reduce fat intake, and to assess relationships between these behaviors and intake of energy from total and saturated fat. DESIGN: Relationships were examined between intake of total and saturated fat from two 24-hour recalls in the US Department of Agriculture's 1994-1996 Continuing Survey of Food Intakes by Individuals and responses to 19 fat-related behavior questions on the follow-up Diet and Health Knowledge Survey (DHKS). SUBJECTS: Data are from a national sample of 5,649 individuals 20 years of age and older. STATISTICAL ANALYSES PERFORMED: Multiple regression models are used to identify dietary behaviors, demographic factors, and personal characteristics that are determinants of fat intake. RESULTS: In this study, the percentage of US adults who consistently followed the low-fat behaviors ranged from 8% to 70%. The most highly adopted behaviors (45% or more of adults) included trimming fat from meat, removing skin from chicken, and eating chips infrequently. The least highly adopted behaviors (15% or less of adults) included eating baked or boiled potatoes without added fat, avoiding butter or margarine on breads, eating low-fat instead of regular cheeses, and having fruit for dessert when dessert is eaten. Together, the 19 fat-related behavior questions on the DHKS formed a statistically significant predictor for total fat and saturated fat intake, expressed as a percent of energy (P<.0001). Key behaviors in terms of their predicted effect on lowering both total and saturated fat intake were never adding fat to baked or boiled potatoes, not eating red meats, eating less than 3 eggs per week, and never eating chicken fried. Predicted effects of these key behaviors in terms of lowering fat intake as a percentage of energy were > or = 1.5 percentage points for total fat and > or = 0.5 percentage point for saturated fat. CONCLUSIONS: Results have applications for designing brief fat assessment instruments and for identifying key nutrition education messages that promote important fat-lowering behaviors.     

Dietary cholesterol and experimental mammary cancer development

The effect of high‐ and low‐fat diets, with and without cholesterol supplementation, on the development of N‐methylnitrosourea (NMU)‐induced mammary tumors was assessed. Diets consisting of 1. high fat (HF) (20% lard), 2. HF + cholesterol, 3. low fat (LF) (4% lard) + cholesterol, and 4. LF were fed to F344 female rats (24 animals/group) 2 days after NMU administration, and cumulative mammary tumor incidence was monitored for a total of 26 weeks. Animals fed HF diets exhibited significantly greater tumor incidences and numbers of tumors/animal than did animals fed LF diets (p < .0001), regardless of whether cholesterol was present in the diet. These results are consistent with the hypothesis that the mammary‐tumor promoting effects of HF diets are exerted primarily by the triglyceride fraction rather than by the nonsaponifiable (sterol) fraction of total dietary fat.