Skip to main content

Some NLM-NCBI services and products are experiencing heavy traffic, which may affect performance and availability. We apologize for the inconvenience and appreciate your patience. For assistance, please contact our Help Desk at info@ncbi.nlm.nih.gov.

The Libyan Journal of Medicine logoLink to The Libyan Journal of Medicine
. 2007 Dec 1;2(4):180–184. doi: 10.4176/070831

Dietary Lipids and Cancer

RA Othman 1
PMCID: PMC3078250  PMID: 21503242

Abstract

For many years, epidemiological studies continued to suggest that high fat diets are linked to an increased incidence of certain cancers. However, whether the oncogenic properties of fat are associated with their quantity rather than the quality has become debatable. Epidemiological studies have been suggesting that n-6 polyunsaturated fatty acids (n-6 PUFA) and saturated fats are more likely to increase the incidence of cancer, whereas monounsaturated fatty acids (MUFA) and n-3 polyunsaturated fatty acids (n-3 PUFA) are more likely to prevent or decrease the chance of carcinogenesis. A firm conclusion cannot be drawn yet because of insufficient research. This paper reviews the current knowledge of the effects of saturated fats, different types of unsaturated fats, and fat-soluble vitamins on the etiology of cancer.

Keywords: cancer; saturated fats; monounsaturated fatty acids, MUFA; n-3 polyunsaturated fatty acids, n-3 PUFA; n-6 polyunsaturated fatty acids, n-6 PUFA; arachidonic acid, AA; eicosanoids; anti-inflammatory; anti-proliferative effects

Background

For more than fifty years dietary fats have been known to play a substantial role in the etiology of cancer [1]. Dietary habits seem to be more easily modified than tobacco smoking cessation or physical exercise habits [2]. Different studies have suggested that a high consumption of fat is related to an increased incidence of breast, colon, pancreatic and prostate cancer [1]. However, this finding is no longer accepted because the oncogenic properties of fat are independent of their caloric content. Much research has indicated that dietary intake of monounsaturated fats, (e.g. olive oil) [1, 3] or n-3 PUFA (e.g. fish oil, flaxseed oil) [46] is inversely correlated with the development of colorectal cancer. It has also been documented that diets high in animal fat and n-6 PUFA contribute to an increased risk of colorectal [7], colon [8] and breast cancer [9].

The mechanism by which dietary n-3 and n-6 PUFA protect or enhance tumor development, respectively, has not been fully investigated, but most of the proposed mechanisms are based on the metabolic fate of these fats and the subsequent biosynthesis of eicosanoids, which exert control over several systems. Fats, particularly saturated fats, may affect hormonal status, modify cell membrane structure and function, cell signaling transduction pathways, and gene expression, and they may even modulate functions of the immune system [10]. It has become necessary to determine the roles of fatty acids in the development of or protection against human cancer. This article will discuss the relationship between cancer on the one hand, and dietary saturated fats and various types of unsaturated fats on the other hand, as well as indicate the mechanisms by which different fatty acids induce or prevent carcinogenesis.

1. Saturated Fats

During the past several decades, it has been shown that high intake of saturated fat, animal fat, and meat is associated with an increased risk of colorectal [11] and breast cancer [12]. These findings are supported by studies that compared risk factors for colon and rectal cancer and showed that dietary animal fat may be associated with increased risk of colon cancer [1315]. However, a large cohort study followed 483,109 men and 619,199 women over 14 years failed to link meat consumption to increased risk of pancreatic cancer [16]. Another prospective study found that saturated fat intake and butter consumption were strongly correlated with an increased risk of pancreatic cancer, whereas energy and carbohydrate intake were inversely proportional to development of pancreatic cancer [17]. Additionally, a multiethnic cohort study showed a 50% increase in pancreatic cancer risk with diets that were high in pork or total red meat but no increased risk was found with dietary intake of poultry, fish, dairy products, eggs, saturated fat or cholesterol [18]. This study indicated that mutagenic compounds produced during the cooking or preservation of food could be the link between consumption of red or processed meat and the increased risk of pancreatic cancer. Although burned and singed meat contains high concentrations of carcinogens and mutagens, a clear link to increased rates of cancer has not been found [19].

A study published in 2007 compared the incidence of colorectal cancer between African Americans (n=17), Native Africans (n=18), and Caucasian Africans (n=17). It found that higher risks of colorectal cancer and mucosal proliferation rates were associated with higher dietary intake of animal products and with larger colonic populations of bacteria producing potentially toxic hydrogen and secondary bile-salts [20].

In one animal study, 120 male F344 rats were injected weekly with azoxymethane, a carcinogen, and fed a high-fat diet containing 20% mixed lipids (HFML). Treatment with HFML for 38 weeks was significantly associated with increased colonic aberrant crypt foci (ACF), early putative preneoplastic lesions of colon neoplasia, increased cyclooxygenase-2 activity (COX-2) and suppressed colonic apoptosis [21]. This large-scale study was the first to show the effect of HFML on colonic carcinogenesis in a well-established animal model. However, these data failed to elucidate how the HFML diet induces tumor formation in the colon.

In another similar study, F344/N rats were fed a diet containing 19% animal fat (beef tallow) and exposed for 26 weeks to tribromomethane (TBM), a drinking water contaminant. A significant and nearly two-fold expansion in ACF was observed in animals whose diets were high in fat compared to those fed a normal diet [22].

The mechanisms by which fats promote tumorigenesis are not fully understood. However, current knowledge indicates that a high fat intake results in increased production of bile acid, which is converted by intestinal bacteria into secondary bile acid and cytotoxic compounds. These compounds may enhance the proliferative activity of the colonic epithelium [1, 20, and 23] by increasing ornithine decarboxylase, which is involved in cell division. They also seem to speed up secondary cellular transduction signals, such as protein kinase C, and modify membrane fluidity by changing the phospholipid composition of the cell membrane, prostaglandin metabolism, and local inflammatory responses, along with increasing COX-2 activity and decreasing apoptosis [21, 2325].

It has been suggested that diets rich in meat and other animal products may be low in plant foods, such as fruits, vegetables, and whole grain cereals [26]. Thus, such diets may have a lower content of certain anti-carcinogenic compounds, such as antioxidants and phytoestrogens or other phytochemicals that exhibit some antiproliferative activity [27, 28].

2. Monounsaturated Fatty Acids

Great effort has been made to clarify the association between consumption of MUFA, particularly oleic acid, and breast-cancer risk. Oils that are rich in MUFA, particularly olive oil, are considered to be the healthiest type of fat. To corroborate the protective role of olive oil by showing a decreased risk of cancer, a case-control study was conducted between 1999 and 2001 on 755 women: 291 cases with breast cancer and 464 controls. It was found that the consumption of ≥ 8.8 g of olive oil per day significantly correlated with a lower risk of breast cancer [29]. In agreement with these observations, a case-control study conducted in Greece showed that the increased intake of olive oil was associated with a lower risk of breast cancer [30]. Likewise, Galeone, et al., conducted a multicenter case-control study in Italy and Switzerland between 1992 and 2000 on 1394 colon cancer patients, 886 rectal cancer patients, and 4765 controls. Their findings demonstrated that olive oil might decrease colon cancer risk but not rectal cancer risk [31].

Olive oil has been shown to reduce the risk not only of breast and colon cancer, but of many other neoplasms as well. In one case control study, 754 individuals with initial primary cancer in the oral cavity and pharynx, together with 1775 controls, were followed between 1992 and 1997 [32]. It was found that consumption of 0.7 g of olive oil daily was associated with a lower risk of oral cancer [32]. In contrast, Elahi, et al., did not observe a protective effect of olive oil against development of breast cancer [33].

In general, the mechanisms underlying the protective role of olive oil against cancer seem to rely on the polyphenolic compounds, the tocopherol content of olive oil, and its fatty acid structure, which prevents free radical-initiated peroxidation. Moreover, Romero, et al., demonstrated in vitro that these substances exert a strong bactericidal activity against eight strains of Helicobacter pylori (the primary cause of peptic, gastric, and duodenal ulcers). Among these phenolic compounds, the dialdehydic form of decarboxymethyl ligstroside aglycon exhibited the strongest bactericidal effect at a concentration as low as 1.3 µg/ml. These results raise the possibility of considering virgin olive oil a chemo-preventive agent for peptic ulcer and gastric cancer [34]. Furthermore, it was hypothesized that olive oil may regulate cancer-related oncogenes. Colomer, et al., showed that exogenous supplementation of cultured breast cancer cells with physiological concentrations of oleic acid (OA) significantly reduced the overexpression of HER2 (Her-2/neu, erbB-2), a well-characterized oncogene playing a key role in the etiology and progression of breast carcinomas [35].

3. n-3 and n-6 Polyunsaturated Fatty Acids (n-3 PUFA)

Several studies have associated high intake of n-6 fatty acids (e.g. corn and safflower oils) with a poor outcome in cancer patients [36, 37], whereas high consumption of n-3 fatty acids (e.g. fish and flaxseed oils) has been linked to a favorable outcome [38, 39]. To confirm these observations, 30 patients with colorectal adenomas were randomly placed in a control group or in a treatment group receiving a highly purified eicosapentaenoic acid (EPA) in free fatty acid form (2 g/day). After three months of treatment, crypt cell proliferation was reduced and apoptosis was increased in normal colonic mucosa of the EPA-treated group as compared to the control group [40]. The authors suggested that metabolism of EPA may lead to the production of 3-series prostaglandins, such as PGE3, which have an inhibiting effect on cell proliferation and COX-2 activity, along with reduction in the mucosal levels of n-6 fatty acid. However, this study did not provide any further insight into the mechanism by which n-3 fatty acids such as EPA elevate mucosal colonic apoptosis [40]. On the contrary, Cheng, et al., showed that EPA and docosahexaenoic acid (DHA) supplementation significantly increased the production of the apoptosis-enhancing protein Bax, indicating that upregulation of Bax protein within normal mucosa could be one mechanism by which EPA increases mucosal apoptosis in the colon [41].

The ameliorative influence of n-3 fatty acids on cancer has also been documented in animal studies. Twenty male F344 rats were fed either high fat fish oil (HFFO) or high fat corn oil (HFCO) diets for 8 weeks and injected with azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF). Rats fed the HFFO diet had a lower incidence of AOM-induced ACF in the proximal colon than rats fed the HFCO diet. In addition, the activity of hepatic glutathione s-transferase (GST), an antioxidant enzyme, and plasma levels of PGE-2, one of the primary prostaglandins formed from the metabolism of AA, were significantly reduced in rats fed the HFFO diet relative to those fed the HFCO diet. This study indicated that HFFO diets could compromise the antioxidant status of the cell by augmenting lipid peroxidation [42]. Flaxseed oil (FO) is a good source of n-3 fatty acids. Supplementing AIN 93G diet with 10% and 20% of flaxseed meal (FSM) or 7% and 14% of FO decreased the incidence of AOM-induced ACF in Fisher 344 male rats [43]. n-3 PUFA may hinder carcinogenesis by a molecular mechanism, such as increased or decreased production of free radicals and reactive oxygen species, repression of AA-derived eicosanoid synthesis, attenuation the expression of vascular cell adhesion molecule (VCAM-1), believed to promote the adhesion of circulating tumor cells to the endothelium, influences on transcription factor activity and signal transduction pathways, modification of estrogen metabolism, and mechanisms involving insulin sensitivity and membrane fluidity, as reviewed [9].

In general, n-6 PUFA appear to possess some carcinogenic properties. However, conjugated linoleic acid (CLA), a naturally occurring n-6 fatty acid found primarily in ruminant meat and dairy products, has been demonstrated to protect against cancer in animal models of chemical carcinogenesis and to inhibit the proliferation of human cancer cell lines [44]. Different mechanisms may be suggested for how CLA inhibits carcinogenesis. First, it is incorporated into the cell membrane as oleic acid and metabolized as linoleic acid, influencing linoleic acid desaturation and elongation. Thereby, it modulates prostaglandin metabolism. Second, it can decrease synthesis of insulin-like growth factor (IGF) II and down-regulate extracellular signal-regulated kinase-1/2 pathway and IGF-I receptor signaling [45]. Third, CLA may increase free retinol levels by enhancing the level of cellular retinol-binding protein (CRBP) mediated by activation of peroxisome proliferator-activated receptor (PPAR)-alpha (PPAR-alpha), known to be a transcription factor for CRBP [46]. In addition, CLA, particularly the t10c12 isomer, suppresses cell proliferation, and induces apoptosis and expression of the pro-apoptotic gene nonsteroidal anti-inflammatory drug-activated gene 1 in human colorectal cancer cells [47]. Furthermore, there are indications that CLA may inhibit growth of cancer cells through induction of cyclin-dependent kinase inhibitor p21CIP1/WAF1, a tumor suppressor protein [48].

4. Fat-soluble vitamins

There are four families of fat-soluble vitamins: A, D, E, and K. These vitamins have been studied in animals and in humans to assess their influence on the growth of cancer cells of different origins. Ohlsson, et al, studied the effect of fat-soluble vitamins on seven cell lines that were obtained from patients with pancreatic adenocarcinoma. They found that the number of pancreatic cancer cells decreased after treatment with vitamin A and D analogues, especially when high concentrations were used. However, combining retinoids with the vitamin D analogue EB 1089 did not enhance its effect. Moreover, vitamin E succinate repressed cell growth in three out of seven cell lines, whereas vitamin K1 increased the number of pancreatic cancer cells in three out of seven cell lines. This study concluded that high concentrations of vitamin A and D analogues attenuated the cell numbers in pancreatic cancer cell lines, whereas vitamins E succinate and K1 had little if any effect [49]. Vitamin K analogues have also been shown to inhibit cancer cell growth through increased protein kinase phosphorylation, a process important in modulation of cellular transduction signals [50].

Vitamin E has been linked to inhibition of the growth of cancer cells [51] as well as to inhibition of UV-induced DNA damage and carcinogenesis in animal models [52], probably by enhancing the glutathione-dependent enzyme system [53]. Following a secondary analysis of the α-tocopherol, Beta-Carotene Cancer Prevention Study (ATBC), it was reported that male smokers who daily received 50 µg of vitamin E (α-tocopherol) had a 41% decline in prostate cancer mortality and a 36% decline in its incidence [54]. In the same line, a large epidemiologic cohort study found that daily intake of 100 µg vitamin E by smokers and those who had recently quit smoking reduced the risk of metastatic or fatal prostate cancer by 44% compared with others who did not receive the vitamin E supplement [55].

Similarly, high values of serum provitamin A and carotenoids were associated with low risks of mortality from lung, stomach, colorectal and liver cancer among a group of Japanese aged from 39 to 85 years and followed for 11.7 years [56]. Vitamin A may attenuate carcinogenesis through its essential role in controlling cell proliferation and differentiation [57]. Taken together, mechanisms underlying the protective effect of fat-soluble vitamins remain uncertain. However, the antioxidant properties of some vitamins and their ability to induce apoptosis may play a significant role in prevention or inhibition of cancer cell growth, respectively. Retinol and provitamin A carotenoids may also decrease cancer risk through other mechanisms, such as inducing cellular differentiation [58].

Conclusion

The studies described here and elsewhere indicate that monounsaturated fat, n-3 PUFA, and fat soluble vitamins may have a profound influence on the prevention and/or suppression of cancer, whereas saturated fat and n-6 PUFA may increase the risk of carcinogenesis. Monounsaturated fat and n-3 fatty acids should be preferred over animal fats and other vegetable fats in the diet. Inconsistency in the literature with regards to the impact of n-3 PUFA on cancer might be due to a) the frequent lack of proper design in studies on humans, b) the supplement dose is often too low or too high, c) inability to define the target populations due to collection of insufficient data from the participants, so that they may not adequately represent the target populations of interest, d) inadequate sample size. Further studies are needed to determine the inductive or protective mechanisms of dietary fats on carcinogenesis in well-designed human studies.

References

  • 1.Cohen LA. Lipid in cancer: An introduction. J Am Oil Chem Soc Cham II. 1992;27(10):791–792. doi: 10.1007/BF02535851. [DOI] [PubMed] [Google Scholar]
  • 2.Platz. EA, Willett WC, Colditz GA, et al. Proportion of colon cancer risk that might be preventable in a cohort of middle-aged US men. Cancer Causes Control. 2000;11:579–588. doi: 10.1023/a:1008999232442. [DOI] [PubMed] [Google Scholar]
  • 3.Quiles JL, Huertas J, Wahle KWJ, Battino M, Mataix J. Granada: Universidad de Granada y Puleva Food; 2001. Aceite de oliva y cáncer. En: Aceite de oliva y salud (J. Mataix) pp. 155–188. [Google Scholar]
  • 4.Caygill CPJ, Charlett A, Hill MJ. Fat, fish, fish oil and cancer. Br J Cancer. 1996;74:159–164. doi: 10.1038/bjc.1996.332. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Singh J, Hamid R, Reddy BS. Dietary Fat and Colon Cancer: Modulation of cyclooxygenase-2 by types and amount of dietary fat during the postinitiation stage of colon carcinogenesis. Cancer research. 1997;57:3465–3470. [PubMed] [Google Scholar]
  • 6.Williams D, Verghese M, Walker LT, Boateng L, et al. Flax seed oil and.ax seed meal reduce the formation of aberrant crypt foci (ACF) in azoxymethane-induced colon cancer in Fisher 344 male rats. Food Chem Toxicol. 2007;45:153–159. doi: 10.1016/j.fct.2006.08.014. [DOI] [PubMed] [Google Scholar]
  • 7.Giovunncci F, Willett WC. Dietary factors and risk of colon cancer. Ann Med. 1994;26:443–452. doi: 10.3109/07853899409148367. [DOI] [PubMed] [Google Scholar]
  • 8.Ames BN, Gold LS, Willett WC. The causes and prevention of cancer. Proc. Natl. Acad. Sci. USA. 1995;92:5258–5265. doi: 10.1073/pnas.92.12.5258. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.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. Am J Clin Nutr. 2004;79:935–945. doi: 10.1093/ajcn/79.6.935. [DOI] [PubMed] [Google Scholar]
  • 10.Escrich E, Solanas M, Moral R, Costa I, Grau L. Are the olive oil and other dietary lipids related to cancer? Experimental evidence. Clin Transl Oncol. 2006;8(12):868–883. doi: 10.1007/s12094-006-0150-5. [DOI] [PubMed] [Google Scholar]
  • 11.Minami Y, Nishino Y, Tsubono Y, Tsuji I, Hisamichi S. Increase of colon and rectal cancer rates in Japan: Trends in incidence rates in Miyagi Prefecture J Epidemiol. 2006;16:240–248. doi: 10.2188/jea.16.240. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Do MH, Lee SS, Jung PJ, Lee MH. Intake of dietary fat and vitamin in correlation to breast cancer risk in Korean women: a case control study. J Korean Med Sci. 2003;18:534–540. doi: 10.3346/jkms.2003.18.4.534. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Giovannucci E. Diet, body weight, and colorectal cancer: a summary of the epidemiologic evidence. J Womens Health. 2003;12:173–181. doi: 10.1089/154099903321576574. [DOI] [PubMed] [Google Scholar]
  • 14.Wei EK, Giovannucci E, Wu K, Rosner B, Fuchs CS, Willett WC, et al. Comparison of risk factors for colon and rectal cancer. Int J Cancer. 2004;108:433–442. doi: 10.1002/ijc.11540. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Vimalachandran D, Ghaneh P, Costello E, Neoptolemos JP. Genetics and prevention of pancreatic cancer. Cancer Control. 2004;11:6–14. doi: 10.1177/107327480401100102. [DOI] [PubMed] [Google Scholar]
  • 16.Coughlin SS, Calle EE, Patel AV, Thun MJ. Predictors of pancreatic cancer mortality among a large cohort of United States adults. Cancer Causes Control. 2000;11:915–923. doi: 10.1023/a:1026580131793. [DOI] [PubMed] [Google Scholar]
  • 17.Stolzenberg-Solomon RZ, Pietinen P, Taylor PR, Virtamo J, Albanes D. Prospective study of diet and pancreatic cancer in male smokers. Am J Epidemiol. 2002;155:783–792. doi: 10.1093/aje/155.9.783. [DOI] [PubMed] [Google Scholar]
  • 18.Nöthlings U, Wilkens LR, Murphy SP, Hankin JH, Henderson BE, Kolonel LN. Meat and Fat Intake as Risk Factors for Pancreatic Cancer: The Multiethnic Cohort Study. J Nat Cancer Inst. 2005;97:1458–1465. doi: 10.1093/jnci/dji292. [DOI] [PubMed] [Google Scholar]
  • 19.Norat T, Riboli E. Meat consumption and colorectal cancer: a review. Nutr Rev. 2001;59:37–47. doi: 10.1111/j.1753-4887.2001.tb06974.x. [DOI] [PubMed] [Google Scholar]
  • 20.O'Keefe SJD, Chung D, Mahmoud N, Sepulveda AR, Manafe M, et al. Why Do African Americans Get More Colon Cancer than Native Africans? J. Nutr. 2007;137:175S–182S. doi: 10.1093/jn/137.1.175S. [DOI] [PubMed] [Google Scholar]
  • 21.Rao CV, Hirose Y, Indranie C, Reddy BS. Modulation of experimental colon tumorigenesis by types and amounts of dietary fatty acids. Cancer Res. 2001;61:1927–1933. [PubMed] [Google Scholar]
  • 22.Geter DR, George MH, Moore TM, Kilburn SR, et al. The effects of a high animal fat diet on the induction of aberrant crypt foci in the colons of male F344/N rats exposed to trihalomethanes in the drinking water. Toxicol Lett. 2004;7;147(3):245–252. doi: 10.1016/j.toxlet.2003.11.006. [DOI] [PubMed] [Google Scholar]
  • 23.Granados S, Quiles J L, Gil A, Ramírez-Tortosa M. C. Dietary lipids and cancer. Nutr Hosp. 2006;21:42–52. [PubMed] [Google Scholar]
  • 24.Mason J. Nutritional chemopreventive of colon cancer. Semin Gastrointest Dis. 2002;13(3):143–153. [PubMed] [Google Scholar]
  • 25.Corrêa Lima MP, Gomes-da-Silva MHG. Colorectal cancer: lifestyle and dietary factors. Nutr Hosp. 2005;20:235–241. [PubMed] [Google Scholar]
  • 26.Terry P, Hu FB, Hansen H, Wolk A. Prospective study of major dietary patterns and colorectal cancer risk in women. Am J Epidemiol. 2001;154(12):1143–1149. doi: 10.1093/aje/154.12.1143. [DOI] [PubMed] [Google Scholar]
  • 27.Sugimura T. Nutrition and dietary carcinogens. Carcinogenesis. 2000;21:387–395. doi: 10.1093/carcin/21.3.387. [DOI] [PubMed] [Google Scholar]
  • 28.Wolk A. Diet, lifestyle and risk of prostate cancer. Acta Oncologica. 2005;44:277–281. doi: 10.1080/02841860510029572. [DOI] [PubMed] [Google Scholar]
  • 29.Garcia-Segovia P, Sanchez-Villegas A, Doreste J, et al. Olive oil consumption and risk of breast cancer in the Canary Islands: a population-based case-control study. Public Health Nutr. 2006;9(1A):163–167. doi: 10.1079/phn2005940. [DOI] [PubMed] [Google Scholar]
  • 30.Trichopoulou A, Katsouyanni K, Stuver S, et al. Consumption of olive oil and specific food groups in relation to breast cancer risk in Greece. J Natl Cancer Inst. 1995;87:110–116. doi: 10.1093/jnci/87.2.110. [DOI] [PubMed] [Google Scholar]
  • 31.Galeone C, Talamini R, Pelucchi C, Negri E, Giacosa A, et al. Fried foods, olive oil and colorectal cancer. Ann Oncol. 2007;18(1):36–39. doi: 10.1093/annonc/mdl328. [DOI] [PubMed] [Google Scholar]
  • 32.Franceschi S, Favero A, Conti E, et al. Food groups, oils and butter and cancer of the oral cavity and pharynx. Br J Cancer. 1999;80:614–620. doi: 10.1038/sj.bjc.6690400. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Elahi-Saadatian M, Norat T, Goudable J, Riboli E. Biomarkers of dietary fat intake and the risk of breast cancer: a meta-analysis. Int J Cancer. 2004;111:584–591. doi: 10.1002/ijc.20284. [DOI] [PubMed] [Google Scholar]
  • 34.Romero C, Medina E, Vargas J, Brenes M, Castro AD. In Vitro Activity of Olive Oil Polyphenols against Helicobacter pylori. J Agric Food Chem. 2007;7;55(3):680–686. doi: 10.1021/jf0630217. [DOI] [PubMed] [Google Scholar]
  • 35.Colomer R, Menendez JA. Mediterranean diet, olive oil and cancer. Clin Transl Oncol. 2006;8(1):15–21. doi: 10.1007/s12094-006-0090-0. [DOI] [PubMed] [Google Scholar]
  • 36.Meschter CL, Connolly JM, Rose DP. Effect of dietary fat on human breast cancer growth and lung metastasis in nude mice. J Natl Cancer Inst. 1991;16;83(20):1491–1495. doi: 10.1093/jnci/83.20.1491. [DOI] [PubMed] [Google Scholar]
  • 37.Sammon AM, Iputo JE. Maize meal predisposes to endemic squamous cancer of the oesophagus in Africa: breakdown of esterified linoleic acid to the free form in stored meal leads to increased intragastric PGE2 production and a low-acid reflux. Med Hypotheses. 2006;67(6):1431–1436. doi: 10.1016/j.mehy.2006.05.037. [DOI] [PubMed] [Google Scholar]
  • 38.Smith LC, Dauchy EM, Dauchy RT, Sauer LA, Blask DE, Davidson LK, Krause JA, Lynch DT. Dietary fish oil deactivates a growth-promoting signaling pathway in hepatoma 7288CTC in Buffalorats. Nutr Cancer. 2006;56(2):204–213. doi: 10.1207/s15327914nc5602_11. [DOI] [PubMed] [Google Scholar]
  • 39.Bommareddy A, Arasada BL, Mathees DP, Dwivedi C. Chemopreventive effects of dietary flaxseed on colon tumor development. Nutr Cancer. 2006;54(2):216–222. doi: 10.1207/s15327914nc5402_8. [DOI] [PubMed] [Google Scholar]
  • 40.Courtney ED, Matthews S, Finlayson C, et al. Eicosapentaenoic acid (EPA) reduces crypt cell proliferation and increases apoptosis in normal colonic mucosa in subjects with a history of colorectal adenomas. Int J Colorectal Dis. 2007;22(7):765–76. doi: 10.1007/s00384-006-0240-4. [DOI] [PubMed] [Google Scholar]
  • 41.Cheng J, Ogawa K, Kuriki K, et al. Increased intake of n3 polyunsaturated fatty acids elevates the level of apoptosis in the normal sigmoid colon of patients polypectomized for adenomas/ tumors. Cancer Lett. 2003;193:17–24. doi: 10.1016/s0304383502007176. [DOI] [PubMed] [Google Scholar]
  • 42.Dommels YE, Heemskerk S, van den Berg H, et al. Effects of high fat fish oil and high fat corn oil diets on initiation of AOM-induced colonic aberrant crypt foci in male F344 rats. Food Chem Toxicol. 2003;41(12):1739–1747. doi: 10.1016/s0278-6915(03)00201-1. [DOI] [PubMed] [Google Scholar]
  • 43.Williams D, Verghese M, Walker LT, et al. Flax seed oil and flax seed meal reduce the formation of aberrant crypt foci (ACF) in azoxymethane-induced colon cancer in Fisher 344 male rats. Food and Chemical Toxicology. 2007;45:153–159. doi: 10.1016/j.fct.2006.08.014. [DOI] [PubMed] [Google Scholar]
  • 44.De La Torre A, Debiton E, Juaneda P, et al. Beef conjugated linoleic acid isomers reduce human cancer cell growth even when associated with other beef fatty acids. Br J Nutr. 2006;95(2):346–352. doi: 10.1079/bjn20051634. [DOI] [PubMed] [Google Scholar]
  • 45.Kim EJ, Kang IJ, Cho HJ, et al. Conjugated linoleic acid down regulates insulin-like growth factor- I receptor levels in HT-29 human colon cancer cells. J Nutr. 2003;133:2675–2681. doi: 10.1093/jn/133.8.2675. [DOI] [PubMed] [Google Scholar]
  • 46.Carta G, Angioni E, Murru E, et al. Modulation of lipid metabolism and vitamin A by conjugated linoleic acid. Prostaglandins Leukot Essent Fatty Acids. 2002;67(2-3):187–191. doi: 10.1054/plef.2002.0417. [DOI] [PubMed] [Google Scholar]
  • 47.Lee SH, Yamaguchi K, Kim JS, et al. Conjugated linoleic acid stimulates an anti-tumorigenic protein NAG-1 in an isomer specific manner. Carcinogenesis. 2006;27(5):972–981. doi: 10.1093/carcin/bgi268. [DOI] [PubMed] [Google Scholar]
  • 48.Lim do Y, Tyner AL, Park JB, et al. Inhibition of colon cancer cell proliferation by the dietary compound conjugated linoleic acid is mediated by the CDK inhibitor p21CIP1/WAF1. J Cell Physiol. 2005;205:107–713. doi: 10.1002/jcp.20380. [DOI] [PubMed] [Google Scholar]
  • 49.Ohlsson B, Albrechtsson E, Axelson J. Vitamins A and D but not E and K decreased the cell number in human pancreatic cancer cell lines. Scand J Gastroenterol. 2004;39(9):882–885. doi: 10.1080/00365520410006701. [DOI] [PubMed] [Google Scholar]
  • 50.Osada S, Saji S, Osada K. Critical role of extracellular signal regulated kinase phosphorylation on menadione (vitamin K3) induced growth inhibition. Cancer. 2001;91:1156–1165. [PubMed] [Google Scholar]
  • 51.Malafa MP, Neitzel LT. Vitamin E succinate promotes breast cancer tumor dormancy. J Surg Res. 2000;93:163–170. doi: 10.1006/jsre.2000.5948. [DOI] [PubMed] [Google Scholar]
  • 52.Berton TR, Conti CJ, Mitchell DL, Aldaz CM, Lubet RA, Fischer SM. The effect of vitamin E acetate on ultravioletinduced mouse skin carcinogenesis. Mol Carcinog. 1998;23(3):175–184. doi: 10.1002/(sici)1098-2744(199811)23:3<175::aid-mc6>3.0.co;2-b. [DOI] [PubMed] [Google Scholar]
  • 53.Van Haaften RI, Haenen GR, Evelo CT, et al. Effect of vitamin E on glutathione-dependent enzymes. Drug Metab Rev. 2003;35(2-3):215–253. doi: 10.1081/dmr-120024086. [DOI] [PubMed] [Google Scholar]
  • 54.Heinonen OP, Albanes D, Virtamo J, Taylor P R, Huttunen J K, Hartman AM, Haapakoski J, Malila N, Rautalahti M, et al. Prostate cancer and supplementation with α-tocopherol and Beta -carotene: incidence and mortality in a controlled trial. J. Natl. Cancer. Inst. 1998;90:440–446. doi: 10.1093/jnci/90.6.440. [DOI] [PubMed] [Google Scholar]
  • 55.Chan JM, Stampfer MJ, Ma J, Rimm EB, Willett WC, Giovannucci E L. Supplemental vitamin E intake and prostate cancer risk in a large cohort of men in the United States. Cancer Epidemiol. Biomarkers Prev. 1999;8:893–899. [PubMed] [Google Scholar]
  • 56.Ito Y, Suzuki K, Ishii J, Hishida H, Tamakoshi A, Hamajima N, Aoki K. A population-based follow-up study on mortality from cancer or cardiovascular disease and serum carotenoids, retinol and tocopherols in Japanese inhabitants. Asian Pac J Cancer Prev. 2006;7(4):533–546. [PubMed] [Google Scholar]
  • 57.Larsson SC, Bergkvist L, Naslund I, et al. Vitamin A, retinol, and carotenoids and the risk of gastric cancer: a prospective cohort study. Am J Clin Nutr. 2007;85(2):497–503. doi: 10.1093/ajcn/85.2.497. [DOI] [PubMed] [Google Scholar]
  • 58.Fairfield KM, Fletcher RH. Vitamins for chronic disease prevention in adults: scientific review. AJMA. 2007;288(14):1720. doi: 10.1001/jama.287.23.3116. [DOI] [PubMed] [Google Scholar]

Articles from The Libyan Journal of Medicine are provided here courtesy of Taylor & Francis

RESOURCES