Design of the Women's Health Initiative clinical trial and observational study

Dietary influences on serum lipids and lipoproteins.

Livestock's Long Shadow

Omega-3 fatty acids as cancer chemopreventive agents.

The 1978-1979 mortality rates for cancers of the breast, prostate, ovary, and colon in 26 to 30 countries were related to the average 1979-1981 food availability data published by the United Nations. The previously described relationship between breast cancer mortality rates and animal fat consumption continues to be evident, and applies also to the other three tumor types. The correlation with breast cancer was particularly strong in postmenopausal women. Since 1964, particularly notable increases in both breast cancer mortality rate and dietary fat intake have occurred in those countries with a relatively low breast cancer risk. The international comparisons support evidence from animal experiments that diets in which olive oil is a major source of fat are associated with reduced breast cancer risk. The excess in mortality rates for breast and ovarian cancer in Israel relative to the national animal fat consumption may be due to the mixed ethnic origin of the Israeli population. Positive correlations between foods and cancer mortality rates were particularly strong in the case of meats and milk for breast cancer, milk for prostate and ovarian cancer, and meats for colon cancer. All four tumor types showed a negative correlation with cereal intake, which was particularly strong in the case of prostate and ovarian cancer. Although, in general, there was a good positive correlation between prostate and breast cancer mortality rates and between prostate cancer and animal fat, discrepancies in national ranking indicate the operation of other etiologic factors that modify risk. The observed positive correlations between the four cancer mortality rates and caloric intake from animal sources, but negative correlations for vegetable-derived calories, suggest that, of the two, animal fat and not energy is the major dietary influence on cancer risk.

International comparisons of mortality rates for cancer of the breast, ovary, prostate, and colon, and per capita food consumption

High fat diets promote the development of mammary tumors induced in rats by 7,12-dimethylbenz(a)anthracene (DMBA), and polyunsaturated fats are more effective than saturated fats. This difference is related to the linoleic acid content of polyunsaturated vegetable oils, but the amount of linoleate required for maximum tumor promotion appears to be higher than indicated by earlier experiments. Comparison of the effects of a polyunsaturated vegetable oil (corn oil) containing linoleate with a fish oil (menhaden oil) containing polyunsaturated fatty acids derived from linolenic acid showed that higher dietary levels of corn oil increased the yield of DMBA-induced mammary tumors, while corresponding levels of menhaden oil had an inhibitory effect. This is further evidence that promotion of mammary tumorigenesis by polyunsaturated vegetable oils may be mediated by prostaglandins or other biologically active eicosanoids derived from n-6 fatty acids.

Dietary polyunsaturated fat in relation to mammary carcinogenesis in rats.

Experimental studies and epidemiologic data both indicate that high-fat diets increase the risk of cancer at sites such as breast, colon, and pancreas. Dietary polyunsaturated vegetable oils promote tumorigenesis in animals whereas saturated fats and polyunsaturated fish oils either have little effect or are inhibitory. A blend of fats typical of the American diet enhanced mammary tumorigenesis effectively when fed as 40% of calories. After 9 to 10 weeks on this diet, reducing the fat to 10% of calories inhibited subsequent tumor development. Although dietary fat appears to act as a promoter, the exact mechanisms are still unknown. Cancer mortality in humans correlates better with total dietary fat than with degree of unsaturation, perhaps because most diets contain more than the amount of polyunsaturated fatty acids required for maximum effect on tumorigenesis in animals. A reduction in total dietary fat is recommended to reduce the current high cancer mortality.

Fat and cancer.

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 epidemiologica...

Dietary fat and mammary carcinogenesis.

Differing effects of dietary polyunsatured vegetable and fish oils on mammary tumorginesis in rats

This study examined the impact of rearing temperature (10.5, 13.5 or 16.5°C) on the hepatic transcriptome of AquAdvantage Salmon (growth hormone transgenic female triploid Atlantic salmon) at an average weight of 800 g. Six stranded PE libraries were Illumina-sequenced from each temperature group, resulting in an average of over 100 M raw reads per individual fish. RNA-sequencing (RNA-seq) results showed the greatest difference in the number of differentially expressed transcripts (1750 DETs), as revealed by both DESeq2 and edgeR (q < 0.05; fold-change > |1.5|), was between the 10.5 and 16.5°C temperature groups. In contrast, 172 and 52 DETs were found in the 10.5 vs. 13.5°C and the 13.5 vs. 16.5°C comparisons, respectively. Considering the DETs between the 10.5 and 16.5°C groups, 282 enriched gene ontology (GO) terms were identified (q < 0.05), including “response to stress”, “immune system process”, “lipid metabolic process”, “oxidation-reduction process”, and “cholesterol metabolic process”, suggesting elevated temperature elicited broad effects on multiple biological systems. Pathway analysis using ClueGO showed additional impacts on amino acid and lipid metabolism. There was a significant positive correlation between RNA-seq and real-time quantitative polymerase chain reaction (RT-qPCR) results for 8 of 9 metabolic-related transcripts tested. RT-qPCR results also correlated to changes in fillet tissue composition previously reported in these salmon (e.g., methionine and lysine concentrations positively correlated with hsp90ab1 transcript expression), suggesting that rearing temperature played a significant role in mediating metabolic/biosynthetic pathways of AquAdvantage Salmon. Many transcripts related to lipid/fatty acid metabolism (e.g., elovl2, fabpi, hacd2, mgll, s27a2, thrsp) were downregulated at 16.5°C compared to both other temperature groups. Additionally, enrichment of stress-, apoptosis- and catabolism-relevant GO terms at 16.5°C suggests that this temperature may not be ideal for commercial production when using freshwater recirculating aquaculture systems (RAS). This study relates phenotypic responses to transcript-specific findings and therefore aids in the determination of an optimal rearing temperature for AquAdvantage Salmon. With approval to grow and sell AquAdvantage Salmon in the United States and Canada, the novel insights provided by this research can help industry expansion by promoting optimal physiological performance and health.

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RNA-Seq Analysis of the Growth Hormone Transgenic Female Triploid Atlantic Salmon (Salmo salar) Hepatic Transcriptome Reveals Broad Temperature-Mediated Effects on Metabolism and Other Biological Processes

Laura M. Braden

Papers

Dietary polyunsaturated fat in relation to mammary carcinogenesis in rats.

Fat and cancer.

Dietary fat and mammary carcinogenesis.

Differing effects of dietary polyunsatured vegetable and fish oils on mammary tumorginesis in rats

RNA-Seq Analysis of the Growth Hormone Transgenic Female Triploid Atlantic Salmon (Salmo salar) Hepatic Transcriptome Reveals Broad Temperature-Mediated Effects on Metabolism and Other Biological Processes