The traditional diet of Greece and cancer.

[R.B.]

Fat -1 is a gene in worms that converts omega 6 to omega 3. Animals and humans do not have that ability.

They have done trial where they insert the gene into pigs and mice and they make Omega 6 into Omega 3 and tend to balance the two.

Here they are seeing what happens to cancer cells if the fat gene is inserted into cancer cells and the cells put into mice.

The fat gene inhibited cell proliferation in prostate cancer.

In essence once again a balance of Omega 3s and 6s / lower Omega 6s may help inhibit cancer.

RB



Expression of the fat-1 gene diminishes prostate cancer growth in vivo through enhancing apoptosis and inhibiting GSK-3{beta} phosphorylation.
Lu Y, Nie D, Witt WT, Chen Q, Shen M, Xie H, Lai L, Dai Y, Zhang J.

Department of Medicine, University of Pittsburgh, VA Pittsburgh Healthcare Systems, Room 2E146, University Drive, Pittsburgh, PA 15240. zhangj2@upmc.edu.

Epidemiologic studies inclusively indicate that "unhealthy" dietary fat intake is one of the potential risk factors for cancer. In dietary fat, there are two types of polyunsaturated fatty acids (PUFA), omega-3 (n-3) and omega-6 (n-6). Numerous studies support that the ratio of n-6/n-3 affects tumorigenesis. It was reported that adenoviral transfer of the fat-1 gene, which converts n-6 to n-3, into breast and lung cancer cells had an antitumor effect in vitro. However, the effects of the fat-1 gene expression on tumor growth in vivo have not been studied and the mechanisms remain unclear. Accordingly, prostate cancer DU145 and PC3 cells were transfected with either the fat-1 gene or a control vector. The cells that expressed the fat-1 gene had a lower n-6/n-3 PUFA ratio compared with the cells that expressed the control vector. The fat-1 gene expression significantly inhibited prostate cancer cell proliferation and invasion in vitro. The fat-1 and control vector-transfected prostate cancer cells were s.c. implanted into severe combined immunodeficient mice for 6 weeks. The fat-1 gene expression significantly diminished tumor growth in vivo, but the control vector had no effect. Finally, we evaluated signaling pathways that may be important for fat-1 gene function. Administration of n-3 PUFA induced caspase-3-mediated prostate cancer cell apoptosis in vitro. The fat-1 gene expression inhibited prostate cancer cell proliferation via reduction of GSK-3beta phosphorylation and subsequent down-regulation of both beta-catenin and cyclin D1. These results suggest that fat-1 gene transfer directly into tumor cells could be used as a novel therapeutic approach. [Mol Cancer Ther 2008;7(10):3203-11].

[R.B.]

Arachidonic acid is the long chain Omega 6 and raw material of the Omega 6 chemicals. COX 2 is one of the enzymes that converts arachidonic acid to its down stream products.

This is another confirmation of a link between oestrogen production and Omega 6.

The vegetable based Omega 6 increases COX 2 expression.

The only place you can get Omega 6 is in the diet you cannot make it.

Long chain Omega 3 has a blocking effect on COX2 Omega 6 products by a variety of mechanisms.


RB



Cyclooxygenase-2 mRNA expression correlates with aromatase expression in human breast cancer.
Salhab M, Singh-Ranger G, Mokbel R, Jouhra F, Jiang WG, Mokbel K.

St. George's University of London, Tooting, London, United Kingdom.

INTRODUCTION: The cyclooxygenase-2 (COX-2), responsible for the conversion of arachidonic acid into prostaglandin (PG) E2, is known to increase intracellular cAMP and estrogen production in malignant breast tissue. The aromatase enzyme complex is responsible for local production of estrogens in breast cancer. Increasing evidence supports a role for COX-2 in upregulation of aromatase activity. The aim of this study was to examine the relationship between COX-2 and aromatase mRNA expression in human breast cancer. METHODS: A total of 160 breast samples (127 tumor tissues and 33 normal tissues) were analyzed. Levels of transcription were determined using real-time quantitative PCR. COX-2 and aromatase mRNA expression were normalized against CK19. Levels of expression of COX-2 were correlated with those of aromatase using Pearson's correlation method. RESULTS: Levels of expression of COX-2/CK19 of both benign and malignant tissues were positively correlated with aromatase/CK19 transcript levels (correlation coefficient = +0.536, P < 0.0001). When we compared levels of expression of both genes in malignant samples only, there was a highly significant positive correlation (r = +0.611, P < 0.00001). CONCLUSION: This study demonstrates a strong positive relationship between COX-2 and aromatase mRNA expression, and lends further support to the hypothesis that COX-2 is an upregulator of aromatase in breast tissue.

[R.B.]

1: Breast Cancer Res Treat. 2007 Jan;101(1):7-16. Epub 2006 Jul 6.Click here to read Links
Differential effects of omega-3 and omega-6 Fatty acids on gene expression in breast cancer cells.
Hammamieh R, Chakraborty N, Miller SA, Waddy E, Barmada M, Das R, Peel SA, Day AA, Jett M.

Division of Pathology, Walter Reed Army Institute of Research, 503 Robert Grant Road, Silver Spring, MD 20910, USA.

Essential fatty acids have long been identified as possible oncogenic factors. Existing reports suggest omega-6 (omega-6) essential fatty acids (EFA) as pro-oncogenic and omega-3 (omega-3) EFA as anti-oncogenic factors. The omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), inhibit the growth of human breast cancer cells while the omega-6 fatty acids induces growth of these cells in animal models and cell lines. In order to explore likely mechanisms for the modulation of breast cancer cell growth by omega-3 and omega-6 fatty acids, we examined the effects of arachidonic acid (AA), linoleic acid (LA), EPA and DHA on human breast cancer cell lines using cDNA microarrays and quantitative polymerase chain reaction. MDA-MB-231, MDA-MB-435s, MCF-7 and HCC2218 cell lines were treated with the selected fatty acids for 6 and 24 h. Microarray analysis of gene expression profiles in the breast cancer cells treated with both classes of fatty acids discerned essential differences among the two classes at the earlier time point. The differential effects of omega-3 and omega-6 fatty acids on the breast cancer cells were lessened at the late time point. Data mining and statistical analyses identified genes that were differentially expressed between breast cancer cells treated with omega-3 and omega-6 fatty acids. Ontological investigations have associated those genes to a broad spectrum of biological functions, including cellular nutrition, cell division, cell proliferation, metastasis and transcription factors etc., and thus presented an important pool of biomarkers for the differential effect of omega-3 and omega-6EFAs.

[R.B.]

Changing your Omega 3 6 intake shows up quite quickly in breast tissue (3 months).

It take about 680 day to change half of your adipose fat.

Fats in blood change quite quickly but still reflect stored Omega 6.

The body heavily stores Omega 6 (Omega 6 is 3-30% of body fat dependent on the amount in the diet) but stores very little Omega 3 (Omega 3 is usually under 1% of body fat and in the West often a fraction of a percent).

Omega 6 increases the risk of cancer and Omega 3s reduce the risk of cancer.

Does concentration of Omega 6 in the breast where the diet is high in Omega 6 could explain why breasts are more susceptible to cancer than part of the body that are less reliant on Omega 3 and 6..

These patients were given 1.8 gram EPA and 1.2 grams DHA a day. The full trial is free.

http://jnci.oxfordjournals.org/cgi/reprint/89/15/1123




Dietary modulation of omega-3/omega-6 polyunsaturated fatty acid ratios in patients with breast cancer.
Bagga D, Capone S, Wang HJ, Heber D, Lill M, Chap L, Glaspy JA.

Department of Medicine, School of Medicine, University of California at Los Angeles, 90095-6956, USA.

BACKGROUND: Polyunsaturated fatty acids of the omega-6 (omega-6) class, as found in corn and safflower oils, can act as precursors for intermediates involved in the growth of mammary tumors when fed to animals, whereas polyunsaturated fatty acids of the omega-3 (omega-3) class, as found in fish oil, can inhibit these effects. The effects of dietary intervention on the ratios of these fatty acids in breast and other adipose tissues have not previously been prospectively studied. PURPOSE: The present investigation was conducted to study the impact on the ratio of omega-3 and omega-6 polyunsaturated fatty acid in plasma and in adipose tissue of the breast and buttocks when women with breast cancer consume a low-fat diet and fish oil supplements. METHODS: Twenty-five women with high-risk localized breast cancer were enrolled in a dietary intervention program that required them to eat a low-fat diet and take a daily fish oil supplement throughout a 3-month period. Breast and gluteal fat biopsy specimens were obtained from each woman before and after dietary intervention. The fatty acid compositions of specimens of plasma, breast fat, and gluteal fat were determined by gas-liquid chromatography. Statistical analysis involved use of a two-sided paired t test. RESULTS: After dietary intervention, a reduction in the level of total omega-6 polyunsaturated fatty acids in the plasma was observed (P<.0003); moreover, total omega-3 polyunsaturated fatty acids increased approximately three-fold (P<.0001) and the omega-3/omega-6 polyunsaturated fatty acids ratio increased approximately fourfold (i.e., mean values increased from 0.09 to 0.41; P = .0001). An increase in total omega-3 polyunsaturated fatty acids in breast adipose tissue was observed following dietary intervention (P = .04); the omega-3/omega-6 polyunsaturated fatty acid ratio increased from a mean value of 0.05 to 0.07 (P = .0001). An increase in total omega-3 polyunsaturated fatty acids was observed in gluteal adipose tissue following the intervention (P = .05); however, the ratio of omega-3 to omega-6 polyunsaturated fatty acids (mean ratio values of 0.036-0.045; P = .06) was unchanged. CONCLUSION: Short-term dietary intervention can lead to statistically significant increases in omega-3/omega-6 polyunsaturated fatty acid ratios in plasma and breast adipose tissue. Breast adipose tissue changed more rapidly than gluteal adipose tissue in response to the dietary modification tested in this study. Therefore, gluteal adipose tissue may not be a useful surrogate to study the effect of diet on breast adipose tissue.

[R.B.]

This is technical and relates to pancreatic cancer and not BC (although it mentions it) and posted for specialists who keep an eye on this thread if any.

But the pathways under discussion are so basic there is undoubtedly some communality, as in the impact of COX blockers like aspirin in BC.

Linoleic acid is the plant based Omega 6.

A way of reducing Omega 6 COX and LOX activity is not to eat excess Omega 6 in the first place, and Omega 3 DHA has been shown to be a natural COX blocker.

The article gives an idea as to how widespread the effects of the products of Omega 6 are.

Lipoxygenase and cyclooxygenase metabolism: new insights in treatment and chemoprevention of pancreatic cancer
Xian-Zhong Ding,1 Rene Hennig,1 and Thomas E Adriancorresponding author1
1Department of Surgery and Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Tarry 4-711, Chicago, IL 60611, U.S.A


http://www.pubmedcentral.nih.gov/art...i?artid=149414


"COX and LOX metabolism of linoleic and arachidonic acids leads to the formation of a variety of metabolically active products with different roles in carcinogenesis. Our understanding of these roles is steadily increasing. This new information is providing a theoretical basis for development of new cancer chemoprevention approaches targeted to COX and LOX activity."

[R.B.]

Erythrocyte fatty acids and risk of proliferative and nonproliferative fibrocystic disease in women in Shanghai, China.
Shannon J, King IB, Lampe JW, Gao DL, Ray RM, Lin MG, Stalsberg H, Thomas DB.

Center for Research on Occupational and Environmental Toxicology, Oregon Health and Science University, Portland, OR.

BACKGROUND: Although benign breast changes are more common than breast cancer, little evidence regarding risk factors for benign breast conditions is available. Omega-3 (n-3) fatty acids have antiinflammatory and antiproliferative actions and may be important in reducing the risk of benign conditions. There is a lack of research on the association of n-3 fatty acids with risk of benign fibrocystic breast changes. OBJECTIVES: The objectives of the study were to evaluate the role of n-3 and other fatty acids in the development of benign proliferative fibrocystic conditions (PFCs) and nonproliferative fibrocystic conditions (NPFCs) in the breast and to evaluate the progression of fibrocystic changes in breast cancer. DESIGN: We conducted a case-control study to determine erythrocyte fatty acid concentrations in 155 women with NPFCs, 185 women with PFCs, 241 women with breast cancer (127 with nonproliferative and 114 with proliferative changes in the noncancerous extratumoral mammary epithelium), and 1030 control subjects. We estimated the relative risk of NPFCs, PFCs, and breast cancer with proliferative and nonproliferative changes in extratumoral tissue compared with the risk of these changes alone. RESULTS: Women in the highest quartile of eicosapentaenoic acid concentrations were 67% less likely to have an NPFC alone or with breast cancer and 49% less likely to have breast cancer than were women with PFCs. gamma-Linolenic acid (18:3n-6) was positively associated with all fibrocystic and cancerous conditions. Palmiticalmitoleic acid (n-7 saturation index) was inversely associated with risk in all comparisons. CONCLUSION: Our results support a protective effects of n-3 fatty acid intake and the n-7 saturation index against benign fibrocystic breast changes and the progression of proliferative changes to breast cancer.

[R.B.]

ALA is the plant based Omega 3.

Nuts are high in Omega 6, as are many processed foods.

Processed foods may also contain oxidised fats, and be low on antioxidants.

Fruit and veg contain antioxidants.

Again the trial generally underlines the importance of diet.

RB



1: Int J Cancer. 2009 Feb 15;124(4):924-31.Click here to read Links
Dietary intakes of omega-6 and omega-3 polyunsaturated fatty acids and the risk of breast cancer.
Thiébaut AC, Chajès V, Gerber M, Boutron-Ruault MC, Joulin V, Lenoir G, Berrino F, Riboli E, Bénichou J, Clavel-Chapelon F.

INSERM, ERI-20, Institut Gustave Roussy, Villejuif Cedex, France.

Experimental studies suggest detrimental effects of omega-6 polyunsaturated fatty acids (PUFA), and beneficial effects of omega-3 PUFAs on mammary carcinogenesis, possibly in interaction with antioxidants. However, PUFA food sources are diverse in human diets and few epidemiologic studies have examined whether associations between dietary PUFAs and breast cancer risk vary according to food sources or antioxidant intakes. The relationship between individual PUFA intakes estimated from diet history questionnaires and breast cancer risk was examined among 56,007 French women. During 8 years of follow-up, 1,650 women developed invasive breast cancer. Breast cancer risk was not related to any dietary PUFA overall; however, opposite associations were seen according to food sources, suggesting other potential effects than PUFA per se. Breast cancer risk was inversely associated with alpha-linolenic acid (ALA) intake from fruit and vegetables [highest vs. lowest quintile, hazard ratio (HR) 0.74; 95% confidence interval (CI) 0.63, 0.88; p trend < 0.0001], and from vegetable oils (HR 0.83; 95% CI 0.71, 0.97; p trend 0.017). Conversely, breast cancer risk was positively related to ALA intake from nut mixes (p trend 0.004) and processed foods (p trend 0.068), as was total ALA intake among women in the highest quintile of dietary vitamin E (p trend 0.036). A significant interaction was also found between omega-6 and long-chain omega-3 PUFAs, with breast cancer risk inversely related to long-chain omega-3 PUFAs in women belonging to the highest quintile of omega-6 PUFAs (p interaction 0.042). These results emphasize the need to consider food sources, as well as interactions between fatty acids and with antioxidants, when evaluating associations between PUFA intakes and breast cancer risk.

[R.B.]

Role of fatty acids in malignancy and visual impairment: epidemiological evidence and experimental studies.
Tsubura A, Yuri T, Yoshizawa K, Uehara N, Takada H.

Department of Pathology II, Kansai Medical University, Takii Hospital, Moriguchi, Osaka, Japan. tsubura@takii.kmu.ac.jp

International variation in breast and colon cancer incidence is positively related to total fat intake. However, total fat consists of different fatty acid families, e.g., saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and n-3 and n-6 polyunsaturated fatty acids (PUFAs). Epidemiological evidence and experimental studies suggest that these fatty acid families have different effects on breast and colon carcinogenesis. Therefore the action of each fatty acid on carcinogenesis should be evaluated separately. Although it is difficult to establish firm conclusions on the effect of each fatty acid in human epidemiological studies, experimental studies on animals and cultured cells suggest that n-6 PUFAs (linoleic acid and arachidonic acid) may have a tumor promoting effect, while n-3 PUFAs (eicosapentaenoic acid, docosahexaenoic acid and alpha-linolenic acid) and conjugated fatty acids (CFAs; a mixture of positional and geometric isomers of PUFAs with conjugated double bonds) exert an inhibitory effect on tumor growth. SFAs such as palmitic acid and stearic acid show little or no tumor promoting effect, and the action of oleic acid, a MUFA, is inconclusive. In addition to regulation of abnormal cell growth seen in cancers, fatty acids also control cell loss seen in degenerative eye diseases, such as degeneration of lens material in cataract and degeneration of photoreceptor cells in retinitis pigmentosa. Experiments suggest that n-6 PUFAs cause deleterious effects, while n-3 PUFAs result in beneficial effects on the lens and retina. In particular, docosahexaenoic acid is known to be effective in rescuing photoreceptor cells from damage. Thus, understanding the function of each fatty acid is likely to be important for making progress in treating these and other diseases.

[R.B.]

To correlate breast cancer outcomes with Omega 3: tissue status you arguably need to look at breast fat at the time of biopsy.

This trial suggests central adipose tissue is not a good marker. Dietary modulation of omega-3/omega-6 polyunsaturated fatty acid ratios in patients with breast cancer. (below)

Adipose buttock tissue saves fats differently again and tends to accumulate more Omega 3 and 6, and significant changes are seen in 3 months. http://www.ncbi.nlm.nih.gov/pubmed/11489728

Modulation of omega-3/omega-6 polyunsaturated ratios with dietary fish oils in men with prostate cancer.

For me this throws into question Omega 3:6 trials on breast cancer looking a buttock fat after the event. http://jnci.oxfordjournals.org/cgi/reprint/85/10/785

Fatty Acid Composition of the Subcutaneous
Adipose Tissue and Risk of Proliferative
Benign Breast Disease and Breast Cancer

Breasts are designed to make milk so probably have fat accumulation and conversion rules all of their own, which might make them more susceptible to fat imbalances (more reading required when I have time).


http://grande.nal.usda.gov/ibids/ind...s&therow=81227

Dietary modulation of omega-3/omega-6 polyunsaturated fatty acid ratios in patients with breast cancer.

BACKGROUND: Polyunsaturated fatty acids of the omega-6 (omega-6) class, as found in corn and safflower oils, can act as precursors for intermediates involved in the growth of mammary tumors when fed to animals, whereas polyunsaturated fatty acids of the omega-3 (omega-3) class, as found in fish oil, can inhibit these effects. The effects of dietary intervention on the ratios of these fatty acids in breast and other adipose tissues have not previously been prospectively studied. PURPOSE: The present investigation was conducted to study the impact on the ratio of omega-3 and omega-6 polyunsaturated fatty acid in plasma and in adipose tissue of the breast and buttocks when women with breast cancer consume a low-fat diet and fish oil supplements. METHODS: Twenty-five women with high-risk localized breast cancer were enrolled in a dietary intervention program that required them to eat a low-fat diet and take a daily fish oil supplement throughout a 3-month period. Breast and gluteal fat biopsy specimens were obtained from each woman before and after dietary intervention. The fatty acid compositions of specimens of plasma, breast fat, and gluteal fat were determined by gas-liquid chromatography. Statistical analysis involved use of a two-sided paired t test. RESULTS: After dietary intervention, a reduction in the level of total omega-6 polyunsaturated fatty acids in the plasma was observed (P less than .0003); moreover, total omega-3 polyunsaturated fatty acids increased approximately three-fold (P less than .0001) and the omega-3/omega-6 polyunsaturated fatty acids ratio increased approximately fourfold (i.e., mean values increased from 0.09 to 0.41; P = .0001). An increase in total omega-3 polyunsaturated fatty acids in breast adipose tissue was observed following dietary intervention (P = .04); the omega-3/omega-6 polyunsaturated fatty acid ratio increased from a mean value of 0.05 to 0.07 (P = .0001). An increase in total omega-3 polyunsaturated fatty acids was observed in gluteal adipose tissue following the intervention (P = .05); however, the ratio of omega-3 to omega-6 polyunsaturated fatty acids (mean ratio values of 0.036-0.045; P = .06) was unchanged. CONCLUSION: Short-term dietary intervention can lead to statistically significant increases in omega-3/omega-6 polyunsaturated fatty acid ratios in plasma and breast adipose tissue. Breast adipose tissue changed more rapidly than gluteal adipose tissue in response to the dietary modification tested in this study. Therefore, gluteal adipose tissue may not be a useful surrogate to study the effect of diet on breast adipose tissue.

[R.B.]

Long-chain n-3-to-n-6 polyunsaturated fatty acid ratios in breast adipose tissue from women with and without breast cancer.
Bagga D, Anders KH, Wang HJ, Glaspy JA.

Division of Hematology-Oncology, Department of Medicine, University of California, Los Angeles School of Medicine, Los Angeles, CA 90095, USA.

Animal studies suggest that dietary polyunsaturated fatty acids (PUFAs) of the n-6 class, found in corn and safflower oils, may be precursors of intermediates involved in the development of mammary tumors, whereas long-chain (LC) n-3 PUFAs, found in fish oil, can inhibit these effects. This case-control study was designed to examine the relationship between the PUFA composition of breast adipose tissue and the risk of breast cancer. Using fatty acid levels in breast adipose tissue as a biomarker of past qualitative dietary intake of fatty acids, we examined the hypothesis that breast cancer risk is negatively associated with specific LC n-3 PUFAs (eicosapentaenoic acid and docosahexaenoic acid) and positively associated with n-6 PUFAs (linoleic acid and arachidonic acid). Breast adipose tissue was collected from 73 breast cancer patients and 74 controls with macromastia. The fatty acid levels were determined by gas-liquid chromatography. A logistic regression model was used to obtain odds ratio estimates while adjusting for age. The age-adjusted n-6 PUFA (linoleic acid and arachidonic acid) content was significantly higher in cases than in controls (P = 0.02). There was a trend in the age-adjusted data suggesting that, at a given level of n-6 PUFA, LC n-3 PUFAs (eicosapentaenoic acid and docosahexaenoic acid) may have a protective effect (P = 0.06). A similar inverse relationship was observed with LC n-3-to-n-6 ratio when the data were adjusted for age (P = 0.09). We conclude that total n-6 PUFAs may be contributing to the high risk of breast cancer in the United States and that LC n-3 PUFAs, derived from fish oils, may have a protective effect.

[R.B.]

N-3 and N-6 fatty acids in breast adipose tissue and relative risk of breast cancer in a case-control study in Tours, France.
Maillard V, Bougnoux P, Ferrari P, Jourdan ML, Pinault M, Lavillonnière F, Body G, Le Floch O, Chajès V.

Laboratoire de Biologie des Tumeurs, Clinique d'Oncologie-Radiothérapie, Service de Gynécologie-Obstétrique, E.A. 2103, Unité de Recherche Associée Université-INRA, CHU, Tours, France.

Experimental studies have indicated that n-3 fatty acids, including alpha-linolenic acid (18:3 n-3) and long-chain n-3 polyunsaturated fatty acids inhibit mammary tumor growth and metastasis. Earlier epidemiological studies have given inconclusive results about a potential protective effect of dietary n-3 polyunsaturated fatty acids on breast cancer risk, possibly because of methodological issues inherent to nutritional epidemiology. To evaluate the hypothesis that n-3 fatty acids protect against breast cancer, we examined the fatty acid composition in adipose tissue from 241 patients with invasive, nonmetastatic breast carcinoma and from 88 patients with benign breast disease, in a case-control study in Tours, central France. Fatty acid composition in breast adipose tissue was used as a qualitative biomarker of past dietary intake of fatty acids. Biopsies of adipose tissue were obtained at the time of surgery. Individual fatty acids were measured as a percentage of total fatty acids, using capillary gas chromatography. Unconditional logistic regression modeling was used to obtain odds ratio estimates while adjusting for age, height, menopausal status and body mass index. We found inverse associations between breast cancer-risk and n-3 fatty acid levels in breast adipose tissue. Women in the highest tertile of alpha-linolenic acid (18:3 n-3) had an odds ratio of 0.39 (95% confidence intervals [CI] = 0.19-0.78) compared to women in the lowest tertile (trend p = 0.01). In a similar way, women in the highest tertile of docosahexaenoic acid (22:6 n-3) had an odds ratio of 0.31 (95% CI = 0.13-0.75) compared to women in the lowest tertile (trend p = 0.016). Women in the highest tertile of the long-chain n-3/total n-6 ratio had an odds ratio of 0.33 (95% confidence interval = 0.17-0.66) compared to women in the lowest tertile (trend p = 0.0002). In conclusion, our data based on fatty acids levels in breast adipose tissue suggest a protective effect of n-3 fatty acids on breast cancer risk and support the hypothesis that the balance between n-3 and n-6 fatty acids plays a role in breast cancer. Copyright 2001 Wiley-Liss, Inc.

[R.B.]

Not as certain as looking at breast tissue but interesting none the less.

A prospective study of association of monounsaturated fat and other types of fat with risk of breast cancer.
Wolk A, Bergström R, Hunter D, Willett W, Ljung H, Holmberg L, Bergkvist L, Bruce A, Adami HO.

Department of Medical Epidemiology, Karolinska Institute, Stockholm, Sweden.

BACKGROUND: Animal studies suggest that monounsaturated and polyunsaturated fat may have opposite effects on the risk of breast cancer. METHODS: We performed a population-based prospective cohort study, including 61,471 women aged 40 to 76 years from 2 counties in central Sweden who did not have any previous diagnosis of cancer; 674 cases of invasive breast cancer occurred during an average follow-up of 4.2 years. All subjects answered a validated 67-item food frequency questionnaire at baseline. Cox proportional hazards models were used to obtain adjusted rate ratio (RR) estimates with 95% confidence intervals (CIs). RESULTS: After mutual adjustment of different types of fat, an inverse association with monounsaturated fat and a positive association with polyunsaturated fat were found. The RR for each 10-g increment in daily intake of monounsaturated fat was 0.45 (95% CI, 0.22-0.95), whereas the RR for a 5-g increment of polyunsaturated fat was 1.69 (95% CI, 1.02-2.78); the increments correspond to approximately 2 SDs of intake in the population. Comparing the highest quartile of intake with the lowest, we found an RR of 0.8 (95% CI, 0.5-1.2) for monounsaturated fat and 1.2 (95% CI, 0.9-1.6) for polyunsaturated fat. Saturated fat was not associated with the risk of breast cancer. CONCLUSIONS: Our results indicate that various types of fat may have specific opposite effects on the risk of breast cancer that closely resemble the corresponding effects in experimental animals. Research investigations and health policy considerations should take into account the emerging evidence that monounsaturated fat might be protective for risk of breast cancer.

[R.B.]

Off the track of Omega 3s and 6s but interesting that increased protein decreased risk significantly. It would be interesting to see the whole paper to get a better idea what was going on in their diet, what sort of protein, how it related to fats carbs Omega 3 and 6s etc.


Dietary factors and survival from breast cancer.
Author: Rohan, T E : Hiller, J E : McMichael, A J
Citation: Nutr-Cancer. 1993; 20(2): 167-77

The association between self-reported intake of various dietary factors at diagnosis and survival from breast cancer was studied in a population-based cohort of breast cancer patients in Adelaide, South Australia. These patients had been recruited between 1982 and 1984 into a case-control study of diet and incident breast cancer. Of the 451 patients recruited originally, 412 were followed for a median interval of 5.5 years. There were decreases in the risk of death from breast cancer ranging from 25 to 40% at all levels of energy and protein intake above the baseline, whereas for fat intake there was a 40% increase in risk at the uppermost quintile level. There was also some reduction in risk at the upper levels of intake of beta-carotene and vitamin C. However, there were no dose-dependent variations in risk of death by level of intake for any of the dietary factors studied, and most of the variation in risk that was observed was relatively insubstantial.

[R.B.]

Melatonin is an very powerful antioxidant and is an Omega 6 inflammatory chemical blocker.

Found as usual whilst looking for something else.(-:

Melatonin production in general terms falls post menopause. Obesity and poor sleep are associated with lower melatonin.

Application of melatonin improved mood and reduced depression in post menopausal women.

Depressed melatonin has been noted in some cancers.

Melatonin
By S. R. Pandi-Perumal, Daniel P. Cardinali
http://books.google.com/books?id=m_6...efox-a#PPR7,M1



RB



http://cancerres.aacrjournals.org/cg...ct/65/23/11174

Melatonin-Depleted Blood from Premenopausal Women Exposed to Light at Night Stimulates Growth of Human Breast Cancer Xenografts in Nude Rats


The increased breast cancer risk in female night shift workers has been postulated to result from the suppression of pineal melatonin production by exposure to light at night. Exposure of rats bearing rat hepatomas or human breast cancer xenografts to increasing intensities of white fluorescent light during each 12-hour dark phase (0-345 µW/cm2) resulted in a dose-dependent suppression of nocturnal melatonin blood levels and a stimulation of tumor growth and linoleic acid uptake/metabolism to the mitogenic molecule 13-hydroxyoctadecadienoic acid. Venous blood samples were collected from healthy, premenopausal female volunteers during either the daytime, nighttime, or nighttime following 90 minutes of ocular bright, white fluorescent light exposure at 580 µW/cm2 (i.e., 2,800 lx). Compared with tumors perfused with daytime-collected melatonin-deficient blood, human breast cancer xenografts and rat hepatomas perfused in situ, with nocturnal, physiologically melatonin-rich blood collected during the night, exhibited markedly suppressed proliferative activity and linoleic acid uptake/metabolism. Tumors perfused with melatonin-deficient blood collected following ocular exposure to light at night exhibited the daytime pattern of high tumor proliferative activity. These results are the first to show that the tumor growth response to exposure to light during darkness is intensity dependent and that the human nocturnal, circadian melatonin signal not only inhibits human breast cancer growth but that this effect is extinguished by short-term ocular exposure to bright, white light at night. These mechanistic studies are the first to provide a rational biological explanation for the increased breast cancer risk in female night shift workers.

David E. Blask1, George C. Brainard2, Robert T. Dauchy1, John P. Hanifin2, Leslie K. Davidson1, Jean A. Krause1, Leonard A. Sauer1, Moises A. Rivera-Bermudez3, Margarita L. Dubocovich3, Samar A. Jasser2, Darin T. Lynch1, Mark D. Rollag4 and Frederick Zalatan1

1 Laboratory of Chrono-Neuroendocrine Oncology, Bassett Research Institute, The Mary Imogene Bassett Hospital, Cooperstown, New York; 2 Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania; 3 Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Feinberg School of Medicine, Chicago, Illinois; and 4 Department of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, Bethesda, Maryland

Requests for reprints: David E. Blask, Laboratory of Chrono-Neuroendocrine Oncology, Bassett Research Institute, The Mary Imogene Bassett Hospital, Cooperstown, NY 13326. Phone: 607-547-3677;

[julierene]

This all talks about cancer risk. But what about actually killing cancer cells?

[R.B.]

Long-chain n-3-to-n-6 polyunsaturated fatty acid ratios in breast adipose tissue from women with and without breast cancer.
Bagga D, Anders KH, Wang HJ, Glaspy JA.

Division of Hematology-Oncology, Department of Medicine, University of California, Los Angeles School of Medicine, Los Angeles, CA 90095, USA.

Animal studies suggest that dietary polyunsaturated fatty acids (PUFAs) of the n-6 class, found in corn and safflower oils, may be precursors of intermediates involved in the development of mammary tumors, whereas long-chain (LC) n-3 PUFAs, found in fish oil, can inhibit these effects. This case-control study was designed to examine the relationship between the PUFA composition of breast adipose tissue and the risk of breast cancer. Using fatty acid levels in breast adipose tissue as a biomarker of past qualitative dietary intake of fatty acids, we examined the hypothesis that breast cancer risk is negatively associated with specific LC n-3 PUFAs (eicosapentaenoic acid and docosahexaenoic acid) and positively associated with n-6 PUFAs (linoleic acid and arachidonic acid). Breast adipose tissue was collected from 73 breast cancer patients and 74 controls with macromastia. The fatty acid levels were determined by gas-liquid chromatography. A logistic regression model was used to obtain odds ratio estimates while adjusting for age. The age-adjusted n-6 PUFA (linoleic acid and arachidonic acid) content was significantly higher in cases than in controls (P = 0.02). There was a trend in the age-adjusted data suggesting that, at a given level of n-6 PUFA, LC n-3 PUFAs (eicosapentaenoic acid and docosahexaenoic acid) may have a protective effect (P = 0.06). A similar inverse relationship was observed with LC n-3-to-n-6 ratio when the data were adjusted for age (P = 0.09). We conclude that total n-6 PUFAs may be contributing to the high risk of breast cancer in the United States and that LC n-3 PUFAs, derived from fish oils, may have a protective effect.

[R.B.]

More of the same. (-:

Profound is a word I like (-:

PGE 2 is a direct downstream product of Omega 6, and as above, increases HER2 expression.

PGE 2 is also connected with inflammation and the growth of new cells and blood vessels. If you eat less Omega 6, and reduce your intake below 4%, balance the plant based Omega 3 and 6 fats and get a gram or two of long chain Omega 3 DHA and EPA you will reduce your cancer risk profile.

Nobody makes any money out of telling you to eat LESS Omega 6, in fact the drugs companies would make a lot less, the food producers would have to reformulate most processed foods, margarine producers would be out of a job, and farmers would have to switch to other crops.

You cannot generally sell a negative diet recommendation that has no product attached. It is human nature industry will not be out there marketing eat less Omega 6, because it does not attract advertising budgets, or column inches in a world that takes comfort from being part of the pack. Those with the biggest financial interests would in the short term be shooting themselves in the foot.

In the long term they would be helping to create a healthier happier world and a more secure future for the species, but hey where does that appear on the big company corporate balance sheet, or in the way we value each other.




http://www.ncbi.nlm.nih.gov/pubmed/1...ubmed_RVDocSum
The effect of omega-3 FAs on tumour angiogenesis and their therapeutic potential.
Spencer L, Mann C, Metcalfe M, Webb M, Pollard C, Spencer D, Berry D, Steward W, Dennison A.

Department of HPB and Pancreatic Surgery, Leicester General Hospital, Gwendolen Road, Leicester LE5 4PW, United Kingdom.

Omega-3 fatty acid (omega-3 FA) consumption has long been associated with a lower incidence of colon, breast and prostate cancers in many human populations. Human trials have demonstrated omega-3 FA to have profound anti-inflammatory effects in those with cancer. In vitro and small animal studies have yielded a strong body of evidence establishing omega-3 FA as having anti-inflammatory, anti-apoptotic, anti-proliferative and anti-angiogenic effects. This review explores the evidence and the mechanisms by which omega-3 FA may act as angiogenesis inhibitors and identifies opportunities for original research trialling omega-3 FAs as anti-cancer agents in humans. The conclusions drawn from this review suggest that omega-3 FAs in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) found principally in oily fish have potent anti-angiogenic effects inhibiting production of many important angiogenic mediators namely; Vascular Endothelial Growth Factor (VEGF), Platelet-Derived Growth Factor (PDGF), Platelet-Derived Endothelial Cell Growth Factor (PDECGF), cyclo-oxygenase 2 (COX-2), prostaglandin-E2 (PGE2), nitric oxide, Nuclear Factor Kappa Beta (NFKB), matrix metalloproteinases and beta-catenin.

[Andrea Barnett Budin]

HELLO R.B... I take my Omega 3 EPA (2400) & DHA (1200) daily. Without fail. I watch my Omega 6 intake and try to supplement my supplements w/the right foods (rich in Omega 3). I totally get how out of proportion most diets are and the great benefits of doing all of the above.

In glancing through your book OMEGA SIX THE DEVIL'S FAT I read about many more good reasons to follow this course w/Omega 3's. Obviously on this site we are most concerned with the anti-cancer qualities in Omega 3.

But many of us suffer from muscle pain, arthritis and such. I do believe Omega 3 has anti-inflammatory characteristics that contribute to helping in this area as well as a host of others.

I would love if you would provide us with some info/studies on these, especially the common joint and muscle pain we experience (as side effects of our tx and as we age).

Thanks or keeping us AWARE, R.B.!!

Andi

[Ellie F]

Hi all
Good to see some research from the UK on this important issue.
I have followed this thread with great interest.When I was diagnosed I, like most of us searched for an answer to the 'why me'question.The two things I came up with was a diet loaded with omega 6 processed foods, little omega 3 and a huge amount of stress in the two years before diagnosis.
I wonder if there is any evidence that the chemicals released under stress reduce the amount of omega 3 in the body??
Any views or research?
Ellie

[R.B.]

Oops accidentally deleted.

Sorry

RB