Role of Omega-3 and Vitamin B6 in Cancer Prevention

Role of Omega-3 and Vitamin B6 in Cancer PreventionA critical analysis of the social occasion of omega-3 and vitamin B6 in female genitaliacer prevention received evidence, proposed mechanisms and future directionsAbstractA critical analysis of the power of omega-3 and vitamin B6 in cancer prevention current evidence, proposed mechanisms and future directionsCancer is a leading cause of death worldwide and according to the World Health Organization(WHO accounted for 8.2 million deaths in 2012(1). The complex and dynamic constitution of cancer is evident, however 30% of cancers could be prevented by modifying factors such as diet, not smoking, physical activity and moderate use of alcoholic drink(2). Scientific evidence suggests that nutritionary supplementation of some nutrients can affect the bump of different cancers. For the purposive of this essay I will perform a critical analysis of the role of omega-3 and vitamin B6 in cancer prevention by reviewing the current eviden ce, proposed mechanisms and investigating the future directions of omega-3 and vitamin B6 use in cancer prevention.Omega-3(n-3) and omega-6(n-6) unsaturated fat bitters(PUFAs) argon essential fatty acids that cannot be made by the human body and therefore must be obtained from the diet. The use of n-3 PUFAs in a number of continuing diseases such as coronary artery disease, psoriasis, irritable bowel syndrome and rheumatoid arteritis has been associated with health benefits. Increasing evidence from animal and in vitro studies indicate that n-3 PUFAs, especially eicosapentaenoic acid (EPA) and docosahexaenoic(DHA) acid play a role in inhibiting cancer progression(3). However epidemiological data on the association between n-3 PUFA phthisis and cancer pretend appears to be somewhat less consistent.High fat intake, typically seen in western diets is associated with an increase risk for cancer development. N-3 PUFAs argon an exception as studies put one across institute that n-3 PUFAs cast off protective functions in prostatic, pancreatic, front and colon cancer. Western diets typically contain a steep n-6 to n-3 ratio which has been found is positively associated with prostate cancer development. A get hold of carried out in Jamaican men who had a last ratio of dietary n-6 to n-3 ratio, found that n-6 PUFAs was positively correlated with prostate carcinogenesis while n-3 PUFAs inhibited cancer growth(4). In sympathy with this sketch a case control study of 79 prostate cancer cases and 187 controls, found a high ratio of n-6 to n-3 PUFAs increased the overall risk of prostate cancer in white men and possibly increase the risk of a high grade prostate cancer in all men(5).Population based studies tolerate found that the use of n-3 PUFAs ar protective against cancer development. A community based prospective cohort study of 90,296 subjects found that a diet rich in n-3 fish or n-3 PUFA appeared to protect against the development of hepato mobile phoneular carcinoma (6). In agreement with this study a population-based prospective study in Japan found an reverse relationship between n-3 PUFA intake and the risk of cancer in the proximal site of the large bowel(7). However not all studies have found beneficial effects of the use of n-3 PUFAs in cancer prevention. A French study comprising of over 56,000 women, who were followed for eight years found no associated between n-3 PUFA and breast cancer risk(8).Numerous mechanisms have been proposed for the beneficial effects of n-3 PUFAs in cancer prevention. PUFAs are capable of influencing the fatty acid composition of glycerophospholipids in cell membranes. N-3 PUFAs can replace n-6 PUFAs in glycerophospholipids(9) and a high n-3 to n-6 ratio has been found to affect cell membrane signalling. Lipid rafts are important signalling domains within the cell membrane which contain receptors such as epidermal growth factor receptor(10). As DHA has a poor affinity for cholesterol in l ipid rafts it can supress raft associated signal transduction(10). This is important as in many cancers signalling pathways can be over activated. It has in any case been suggested that n-3 PUFAs may induce apoptosis and reduce proliferation in human cancer cells by decreasing signalling through AKT/NFkB and by modulating the PI3k/AKT/p38 MAPK pathway(11).N-3 PUFAs are involved in the suppression of arachadonic acid (4n-6) derived eicosanoids, which are involved in cellular growth, cell differentiation and have proinflammatory effects (12). Arachadonic derived eicosanoids such as PGE2, have been positively linked to cancer (13), unlike EPA eicosanoids which have anticancer effects(14). As mentioned above incorporation of n-3 PUFAs into the phospholipid membrane replaces n-6 arachadonic acid precursors, decreasing arachadonic derived eicosanoids and increasing EPA eicosanoids. N-3 PUFAs have similarly been found to supress cyclooxygenase-2 (15), which has anti-tumour affects as COX -2 down regulates apoptotic pathways(16). This is in contrast to n-6 PUFAs which have been found to upregulate COX-2(17). It is also interesting to note that in breast, colon and prostate cancer COX-2 is overexpressed (18, 19). Taking this into account it is likely that suppression of COX-2 by n-3 PUFAs may be a preventative measure in these cancers.In ratiocination there is evidence for the beneficial effects of n-3 PUFAs in cancer prevention, however due to inconsistencies in epidemiological data it is too first to recommend the use of n-3 PUFAs for cancer prevention. Possible explanations to explain these inconsistencies may be that population-based studies rely heavily on data from self-reported dietary PUFA intake. This form of data allurement may poorly correlate with accurate PUFA intake. Another possible explanation is that the amount of n-3 PUFA administered in studies, may not be of a sufficient amount of money to have a protective functions in cancer prevention. Furth er studies are needed to be carried out to account for the current variation in published studies before recommending n-3 PUFAs for cancer prevention.According to the latest report from the topic Cancer Registry Colorectal cancer (CRC) is the second almost common cancer in both men and women in Ireland (20). Environmental factors such as diet have been identified as playing a role in the risk of CRC development. Preventability estimates from the World Cancer Research Fund show that 47% of cases of CRC in the UK can be prevented by modifying factors such as eating and drinking healthily, be physically active and maintaining a healthy weight(21). According to the National Health and living Examination Survey 2003-2004 24% of people (who did not take supplements containing vitamin B6) have suboptimal active B6 plasma concentrations (22).Vitamin B6 is a water soluble vitamin, which in its active form pyridoxal 5-phostphate (PIP) is involved in more than than 100 coenzyme reactions , including lipid, simoleons and protein metabolism(23). Vitamin B6 may play a role in CRC prevention through its role in one ampere-second related DNA synthesis and methylation(24). Vitamin B6 has also been shown to reduce the formation of nitric oxide(25), inhibit angiogenesis(26) and reduce oxidative stress(27), creating an unfavourable environment for tumour development.Despite the mechanistic evidence supporting for the role of vitamin B6 in CRC cancer prevention, epidemiological evidence has been inconsistent. A meta-analysis of 9 studies carried out between 2002-2009 on Vitamin B6 intake in relation to CRC risk, found inconsistent results with both an inverse and positive association(28). The same meta-analysis included four nestled case-control studies investigating serum PLP on CRC risk. All four studies found an inverse relationship between PLP levels and CRC risk, with an overall reduced risk of CRC for every 100-pmol/mL increase in serum PLP(28). In the 9 studies of vi tamin B6 intake and CRC risk it seems that highest vs lowest category of vitamin B6 intake was most important. When the studys results were pooled together, a 21% significant reduction in CRC risk was found when comparing high vs low vitamin B6 intake in studies with a wider range of exposure (1.5-mg difference)(28).A different study prospectively followed up 26,440 women and 44,410 men to assess whether a higher vitamin B6 intake in the remote past(12-16years prior to diagnosis) was more strongly associated with a lower risk of developing CRC than an intake in the recent past (4 years prior to diagnosis)(23). The results of this study did not support a strong role of vitamin B6 intake in preventing CRC development. However most of the participants were relatively well nourished, with only 5-10% of people having a vitamin B6 intake below the recommended daily allowance(23). This bound the study as it is not the most accurate measures of determining the potential effects on suboptim al vitamin B6 on CRC risk.The Japan Public Health Centre-based Prospective study investigated the association of dietary pteroylmonoglutamic acid, vitamin B6, vitamin B12 and methionine on CRC risk(29). The study included 81,184 participants (38,107 men and 43,077 women) who were followed from 1995-98 to the end of 2002. A significantly inverse relationship between vitamin B6 intake and CRC was found in men. Men in the highest quartile of vitamin B6 intake had a 35% decreased risk of CRC compared with men in the lowest quartile. No association was found in vitamin B6 intake and CRC in women. Interestingly a higher intake of vitamin B6 appeared to be beneficial in men with higher alcohol intake. The study found that the risk of CRC associated with alcohol intake was significantly higher in those who had a low vitamin B6 intake, however this risk was found to decrease in those who had a higher vitamin B6 intake(29).In conclusion there is evidence to suggest that vitamin B6 may play a role in CRC prevention, however it appears that plasma PLP appears to be more strongly linked to a reduced risk in CRC. Studies investigating the effect of vitamin B6 intake on CRC risk appear to be inconsistent. In contrast studies on PLP have found higher plasma PLP CRC risk by 30-50%(23). It is also important to note that studies have found that individuals with higher activity levels, higher dietary intakes of folate and atomic number 20 and individuals who do not smoke have higher vitamin B6 levels and a decreased risk of CRC(23). In these individuals it is difficult to determine if it is these healthier behaviours or the increased B6 levels that decreases CRC risk. It is also difficult to assess the impact of dietary vitamin B6 on its own on CRC risk, as most foods containing vitamin B6 contain various other nutrients such as folate and vitamin D. Further studies are needed to be carried out to explain the currentinconsistencies in the use of vitamin B6 and CRC risk before v itamin B6 can be recommended as a preventive measure.1.International Agency for Research on Cancer WHO. GLOBOCAN 2012 Estimated Cancer Incidence, Mortality and Prevalence in 2012 2012. Available from http//globocan.iarc.fr/Pages/fact_sheets_cancer.aspx.2.Organization WH. Cancer fact sheet 2014 updated February 2014. Available from http//www.who.int/mediacentre/factsheets/fs297/en/index.html.3.Parada B, Reis F, Cerejo R, Garrido P, Sereno J, Xavier-Cunha M, et al. Omega-3 fatty acids inhibit tumor growth in a rat model of bladder cancer. BioMed research international. 20132013368178.4.Ritch CR, Wan RL, Stephens LB, Taxy JB, Huo D, Gong EM, et al. Dietary fatty acids correlate with prostate cancer biopsy grade and volume in Jamaican men. The Journal of urology. 2007177(1)97-101 discussion5.Williams CD, Whitley BM, Hoyo C, Grant DJ, Iraggi JD, Newman KA, et al. A high ratio of dietary n-6/n-3 polyunsaturated fatty acids is associated with increased risk of prostate cancer. Nutrition re search (New York, NY). 201131(1)1-8.6.Sawada N, Inoue M, Iwasaki M, Sasazuki S, Shimazu T, Yamaji T, et al. Consumption of n-3 fatty acids and fish reduces risk of hepatocellular carcinoma. Gastroenterology. 2012142(7)1468-75.7.Sasazuki S, Inoue M, Iwasaki M, Sawada N, Shimazu T, Yamaji T, et al. Intake of n-3 and n-6 polyunsaturated fatty acids and development of colorectal cancer by subsite Japan Public Health Center-based prospective study. International journal of cancer Journal international du cancer. 2011129(7)1718-29.8.Thiebaut AC, Chajes V, Gerber M, Boutron-Ruault MC, Joulin V, Lenoir G, et al. Dietary intakes of omega-6 and omega-3 polyunsaturated fatty acids and the risk of breast cancer. International journal of cancer Journal international du cancer. 2009124(4)924-31.9.Gu Z, Wu J, Wang S, Suburu J, Chen H, Thomas MJ, et al. Polyunsaturated fatty acids affect the localization and augury of PIP3/AKT in prostate cancer cells. Carcinogenesis. 201334(9)1968-75.10.Turk HF, B arhoumi R, Chapkin RS. Alteration of EGFR spatiotemporal dynamics suppresses signal transduction. PloS one. 20127(6)e39682.11.Schley PD, Jijon HB, Robinson LE, Field CJ. Mechanisms of omega-3 fatty acid-induced growth inhibition in MDA-MB-231 human breast cancer cells. Breast cancer research and treatment. 200592(2)187-95.12.Larsson SC, Kumlin M, Ingelman-Sundberg M, Wolk A. Dietary long-chain n-3 fatty acids for the prevention of cancer a review of potential mechanisms. The American journal of clinical nutrition. 200479(6)935-45.13.Cheuk BL, quid SB, Fiscus RR, Wong PY. Cyclooxygenase-2 regulates apoptosis in rat epididymis through prostaglandin D2. Biology of reproduction. 200266(2)374-80.14.Cockbain AJ, Volpato M, Race AD, Munarini A, Fazio C, Belluzzi A, et al. Anticolorectal cancer activity of the omega-3 polyunsaturated fatty acid eicosapentaenoic acid. Gut. 2014.15.Hamid R, Singh J, Reddy BS, Cohen LA. Inhibition by dietary menhaden oil of cyclooxygenase-1 and -2 in N-nitros omethylurea-induced rat mammary tumors. International journal of oncology. 199914(3)523-8.16.Rose DP, Connolly JM. Omega-3 fatty acids as cancer chemopreventive agents. Pharmacology therapeutics. 199983(3)217-44.17.Badawi AF, bowman MC. Effect of hormonal status on the expression of the cyclooxygenase 1 and 2 genes and prostaglandin synthesis in rat mammary glands. Prostaglandins other lipid mediators. 199856(2-3)167-81.18.Williams CS, Mann M, DuBois RN. The role of cyclooxygenases in inflammation, cancer, and development. Oncogene. 199918(55)7908-16.19.Dempke W, Rie C, Grothey A, Schmoll HJ. Cyclooxygenase-2 a novel target for cancer chemotherapy? Journal of cancer research and clinical oncology. 2001127(7)411-7.20.Registry NC. Cancer In Ireland Annual report of the National Registry. 2013.21.Fund WCR. Policy and Action for Cancer Prevention. Food, Nutrition, and Physical activity a Global Perspective. 2009 updated 2011.22.Morris MS, Picciano MF, Jacques PF, Selhub J. Plasma pyr idoxal 5-phosphate in the US population the National Health and Nutrition Examination Survey, 2003-2004. The American journal of clinical nutrition. 200887(5)1446-54.23.Zhang XH, Ma J, Smith-Warner SA, Lee JE, Giovannucci E. Vitamin B6 and colorectal cancer current evidence and future directions. World journal of gastroenterology WJG. 201319(7)1005-10.24.Selhub J. Folate, vitamin B12 and vitamin B6 and one carbon metabolism. The journal of nutrition, health aging. 20026(1)39-42.25.Komatsu S, Watanabe H, Oka T, Tsuge H, Kat N. Dietary vitamin B6 suppresses colon tumorigenesis, 8-hydroxyguanosine, 4-hydroxynonenal, and inducible nitric oxide synthase protein in azoxymethane-treated mice. Journal of nutritional science and vitaminology. 200248(1)65-8.26.Matsubara K, Mori M, Matsuura Y, Kato N. Pyridoxal 5-phosphate and pyridoxal inhibit angiogenesis in serum-free rat aortic ring assay. International journal of molecular medicine. 20018(5)505-8.27.Jain SK, Lim G. Pyridoxine and pyrido xamine inhibits superoxide radicals and prevents lipid peroxidation, protein glycosylation, and (Na+ + K+)-ATPase activity reduction in high glucose-treated human erythrocytes. Free radical biology medicine. 200130(3)232-7.28.Larsson SC, Orsini N, Wolk A. Vitamin B6 and risk of colorectal cancer a meta-analysis of prospective studies. JAMA the journal of the American Medical Association. 2010303(11)1077-83.29.Ishihara J, Otani T, Inoue M, Iwasaki M, Sasazuki S, Tsugane S. Low intake of vitamin B-6 is associated with increased risk of colorectal cancer in Japanese men. The Journal of nutrition. 2007137(7)1808-14.