Dr. Ron’s Research Review – June 8, 2011

This week’s research review focuses on EFA’s and cancer.

No fatty acids were associated with low-grade prostate cancer risk. Docosahexaenoic acid was positively associated with high-grade disease; TFA 18:1 and TFA 18:2 were linearly and inversely associated with risk of high-grade prostate cancer. (Brasky, Till et al. 2011)

Another study showed an increased risk of prostate cancer in men with a high intake or blood level of alpha-linolenic acid (ALA). (Brouwer 2008)

Tissue levels of dihomo-gamma-linolenic acid, (C20:3w6), an omega-6 PUFA and a major precursor of omega-6 PUFA metabolites, were significantly higher in malignant compared with benign tissues (P = 0.002). Tissue levels of the downstream omega-6 metabolites, arachidonic acid (AA) (20:4omega6), and adrenic acid, (22:4omega6), were significantly lower in cancer tissues, (P < 0.0001 and P = 0.013, respectively). Overall, the total levels of omega-6 PUFA were lower in cancer (P = 0.001).  (Schumacher, Laven et al. 2011)

A review and meta-analysis found no strong evidence of a protective association of fish consumption with prostate cancer incidence but showed a significant 63% reduction in prostate cancer-specific mortality. (Szymanski, Wheeler et al. 2011)

A high ratio of dietary n-6/n-3 polyunsaturated fatty acids is associated with increased risk of prostate cancer. (Williams, Whitley et al. 2011)

Genetic variants in the metabolism of omega-6 and omega-3 fatty acids may play a significant role in the determination of nutritional requirements and chronic disease risk. (Simopoulos 2010)

Dr. Ron


Articles

Serum Phospholipid Fatty Acids and Prostate Cancer Risk: Results From the Prostate Cancer Prevention Trial

            (Brasky, Till et al. 2011) Download

Inflammation may be involved in prostate cancer development and progression. This study examined the associations between inflammation-related phospholipid fatty acids and the 7-year-period prevalence of prostate cancer in a nested case-control analysis of participants, aged 55-84 years, in the Prostate Cancer Prevention Trial during 1994-2003. Cases (n = 1,658) were frequency matched to controls (n = 1,803) on age, treatment, and prostate cancer family history. Phospholipid fatty acids were extracted from serum, and concentrations of omega-3, omega-6, and trans-fatty acids (TFAs) were expressed as proportions of the total. Logistic regression models estimated odds ratios and 95% confidence intervals of associations of fatty acids with prostate cancer by grade. No fatty acids were associated with low-grade prostate cancer risk. Docosahexaenoic acid was positively associated with high-grade disease (quartile 4 vs. 1: odds ratio (OR) = 2.50, 95% confidence interval (CI): 1.34, 4.65); TFA 18:1 and TFA 18:2 were linearly and inversely associated with risk of high-grade prostate cancer (quartile 4 vs. 1: TFA 18:1, OR = 0.55, 95% CI: 0.30, 0.98; TFA 18:2, OR = 0.48, 95% CI: 0.27, 0.84). The study findings are contrary to those expected from the pro- and antiinflammatory effects of these fatty acids and suggest a greater complexity of effects of these nutrients with regard to prostate cancer risk.

Omega-3 PUFA: good or bad for prostate cancer?

            (Brouwer 2008) Download

INTRODUCTION: The objective of this meta-analysis was to estimate quantitatively the associations between intake or status of omega-3 polyunsaturated (omega-3 PUFA) fatty acids and occurrence of prostate cancer in observational studies in humans. METHODS: We combined risk estimates across studies using random-effects models. RESULTS: The combined estimate showed an increased risk of prostate cancer in men with a high intake or blood level of alpha-linolenic acid (ALA) (combined relative risk (RR) 1.36; 95% CI 1.08-1.70). The association is stronger in the case-control studies (RR 1.84; 95% CI 1.04-3.25) than in the prospective studies (RR 1.10; 0.91-1.32). Ecosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were not significantly associated with prostate cancer. DISCUSSION: The association between high intake of ALA and prostate cancer is of concern and needs further study. However, the fact that the prospective studies do not show a clear association makes a true effect of intake of ALA on prostate cancer less likely.

A comparative study of tissue omega-6 and omega-3 polyunsaturated fatty acids (PUFA) in benign and malignant pathologic stage pT2a radical prostatectomy specimens

            (Schumacher, Laven et al. 2011) Download

OBJECTIVE: To analyze different polyunsaturated fatty acid (PUFA) tissue levels in malignant compared with benign prostatic tissue from the same prostate specimens. MATERIALS AND METHODS: Fresh frozen benign and malignant prostatic tissue was obtained from radical prostatectomy specimens in 49 men with pathologic stage pT2a prostate cancer. Histopathologic examination confirmed that all tissues from each prostate being analyzed were either completely benign or almost totally malignant. The PUFA composition in these tissues was determined by gas-liquid chromatography on a capillary column. The relative amount of each PUFA (% of total fatty acids) was quantified by integrating the area under the peak and dividing the result by the total area of all fatty acids. RESULTS: Tissue levels of dihomo-gamma-linolenic acid, (C20:3w6), an omega-6 PUFA and a major precursor of omega-6 PUFA metabolites, were significantly higher in malignant compared with benign tissues (P = 0.002). Tissue levels of the downstream omega-6 metabolites, arachidonic acid (AA) (20:4omega6), and adrenic acid, (22:4omega6), were significantly lower in cancer tissues, (P < 0.0001 and P = 0.013, respectively). Overall, the total levels of omega-6 PUFA were lower in cancer (P = 0.001). CONCLUSION: We found that the omega-6 PUFA AA and adrenic acid are decreased in malignant prostatic tissues compared with benign tissues from the same prostates. These findings provide additional evidence that dietary fat is associated with prostatic carcinogenesis.

Enhancing cytotoxic therapies for breast and prostate cancers with polyunsaturated fatty acids

            (Shaikh, Brown et al. 2010) Download

The role of omega-3 and omega-6 fatty acids has been extensively studied in most of the human malignancies including breast, colon, prostate, pancreas, and stomach cancers. In particular, the role of omega-3 and omega-6 fatty acids in carcinogenesis has been extensively investigated in epidemiological, laboratory cell culture studies and studies in vivo in animal. Findings from these studies suggest that omega-3 and omega-6 fatty acids are cytotoxic in different cancers and act synergistically with cytotoxic drugs. Although experimental evidence for the potential beneficial role of polyunsaturated fatty acids (PUFAs) in enhancing the effectiveness of various chemotherapeutic agents in animal models and in cell culture studies is increasing, there are only a few reports that have shown supportive evidence for linking these natural compounds with augmentation of anticancer chemotherapeutics in human trials. This review presents evidence for a commonality in the proposed molecular mechanisms of action elicited by various PUFAs believed to be responsible for their enhancement of the effectiveness of anticancer chemotherapy, specifically in breast and prostate cancers, and reviews laboratory and animal studies and few reported human clinical trials. It concludes that sufficient evidence is available to suggest that major clinical trials with these natural compounds as adjuncts to standard therapies should be undertaken as a priority.

Genetic variants in the metabolism of omega-6 and omega-3 fatty acids: their role in the determination of nutritional requirements and chronic disease risk

            (Simopoulos 2010) Download

The tissue composition of polyunsaturated fatty acids is important to health and depends on both dietary intake and metabolism controlled by genetic polymorphisms that should be taken into consideration in the determination of nutritional requirements. Therefore at the same dietary intake of linoleic acid (LA) and alpha-linolenic acid (ALA), their respective health effects may differ due to genetic differences in metabolism. Delta-5 and delta-6 desaturases, FADS1 and FADS2, respectively, influence the serum, plasma and membrane phospholipid levels of LA, ALA and long-chain polyunsaturated fatty acids during pregnancy, lactation, and may influence an infant's IQ, atopy and coronary heart disease (CHD) risk. At low intakes of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), polymorphisms at the 5-lipoxygenase (5-LO) level increase the risk for CHD whereas polymorphisms at cyclooxgenase-2 increase the risk for prostate cancer. At high intakes of LA the risk for breast cancer increases. EPA and DHA influence gene expression. In future, intervention studies on the biological effects of LA, ALA and LC-PUFAs, and the effects of genetic variants in FADS1 and FADS2, 5-LO and cyclooxygenase-2 should be taken into consideration both in the determination of nutritional requirements and chronic disease risk. Furthermore, genome-wide association studies need to include environmental exposures and include diet in the interaction between genetic variation and disease association.

Fish consumption and prostate cancer risk: a review and meta-analysis

            (Szymanski, Wheeler et al. 2011) Download

BACKGROUND: Prostate cancer incidence varies 60-fold globally, which suggests the roles of lifestyle and dietary factors in its cause. To our knowledge, a comprehensive assessment of the association between fish consumption and prostate cancer incidence and mortality has not been reported. OBJECTIVE: We conducted a meta-analysis of fish intake and prostate cancer by focusing on the incidence of prostate cancer and prostate cancer-specific mortality and included subgroup analyses based on race, fish type, method of fish preparation, and high-grade and high-stage cancer. DESIGN: We searched MEDLINE and EMBASE databases (May 2009) for case-control and cohort studies that assessed fish intake and prostate cancer risk. Two authors independently assessed eligibility and extracted data. RESULTS: There was no association between fish consumption and a significant reduction in prostate cancer incidence [12 case-control studies (n = 5777 cases and 9805 control subjects), odds ratio (OR): 0.85; 95% CI: 0.72, 1.00; and 12 cohort studies (n = 445,820), relative risk (RR): 1.01; 95% CI: 0.90, 1.14]. It was not possible to perform a meta-analysis for high-grade disease (one case-control study, OR: 1.44; 95% CI: 0.58, 3.03), locally advanced disease (one cohort study, RR: 0.80; 95% CI: 0.61, 1.13), or metastatic disease (one cohort study, RR: 0.56; 95% CI: 0.37, 0.86). There was an association between fish consumption and a significant 63% reduction in prostate cancer-specific mortality [4 cohort studies (n = 49,661), RR: 0.37; 95% CI: 0.18, 0.74]. CONCLUSION: Our analyses provide no strong evidence of a protective association of fish consumption with prostate cancer incidence but showed a significant 63% reduction in prostate cancer-specific mortality.

A high ratio of dietary n-6/n-3 polyunsaturated fatty acids is associated with increased risk of prostate cancer

            (Williams, Whitley et al. 2011) Download

Experimental studies suggest omega-3 (n-3) polyunsaturated fatty acids (PUFA) suppress and n-6 PUFA promote prostate tumor carcinogenesis. Epidemiologic evidence remains inconclusive. The objectives of this study were to examine the association between n-3 and n-6 PUFA and prostate cancer risk and determine if these associations differ by race or disease aggressiveness. We hypothesize that high intakes of n-3 and n-6 PUFA will be associated with lower and higher prostate cancer risk, respectively. A case-control study comprising 79 prostate cancer cases and 187 controls was conducted at the Durham VA Medical Center. Diet was assessed using a food frequency questionnaire. Logistic regression analyses were used to obtain odds ratios (ORs) and 95% confidence intervals (95% CI) for the associations between n-3 and n-6 PUFA intakes, the dietary ratio of n-6/n-3 fatty acids, and prostate cancer risk. Our results showed no significant associations between specific n-3 or n-6 PUFA intakes and prostate cancer risk. The highest dietary ratio of n-6/n-3 was significantly associated with elevated risk of high-grade (OR, 3.55; 95% CI, 1.18-10.69; P(trend) = 0.03), but not low-grade prostate cancer (OR, 0.95; 95% CI, 0.43-2.17). In race-specific analyses, an increasing dietary ratio of n-6/n-3 fatty acids correlated with higher prostate cancer risk among white men (P(trend) = 0.05), but not black men. In conclusion, our findings suggest that a high dietary ratio of n-6/n-3 fatty acids may increase the risk of overall prostate cancer among white men and possibly increase the risk of high-grade prostate cancer among all men.


References

Brasky, T. M., C. Till, et al. (2011). "Serum Phospholipid Fatty Acids and Prostate Cancer Risk: Results From the Prostate Cancer Prevention Trial." Am J Epidemiol.

Brouwer, I. A. (2008). "Omega-3 PUFA: good or bad for prostate cancer?" Prostaglandins Leukot Essent Fatty Acids 79(3-5): 97-9.

Schumacher, M. C., B. Laven, et al. (2011). "A comparative study of tissue omega-6 and omega-3 polyunsaturated fatty acids (PUFA) in benign and malignant pathologic stage pT2a radical prostatectomy specimens." Urol Oncol.

Shaikh, I. A., I. Brown, et al. (2010). "Enhancing cytotoxic therapies for breast and prostate cancers with polyunsaturated fatty acids." Nutr Cancer 62(3): 284-96.

Simopoulos, A. P. (2010). "Genetic variants in the metabolism of omega-6 and omega-3 fatty acids: their role in the determination of nutritional requirements and chronic disease risk." Exp Biol Med (Maywood) 235(7): 785-95.

Szymanski, K. M., D. C. Wheeler, et al. (2011). "Fish consumption and prostate cancer risk: a review and meta-analysis." Am J Clin Nutr 92(5): 1223-33.

Williams, C. D., B. M. Whitley, et al. (2011). "A high ratio of dietary n-6/n-3 polyunsaturated fatty acids is associated with increased risk of prostate cancer." Nutr Res 31(1): 1-8.