Current evidence linking polyunsaturated fatty acids with cancer risk and progression

Frontiers in Oncology

Volumn 3 SEP, Issue , 2013, Pages

  Azrad, Maria ^a   Turgeon, Chelsea ^b   Demark Wahnefried, Wendy ^a  

^a UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

^b UNIVERSITY OF ALABAMA SCHOOL OF MEDICINE   (United States)

Author keywords

Cancer; Clinical trials; Clinical trials as topic; Epidemiologic studies; Phase II as topic; Polyunsaturated fatty acids; Pre clinical testing; Review of literature

Indexed keywords

13 S HYDROXYOCTADECADIENOIC ACID; ACYL COENZYME A DESATURASE 1; ARACHIDONATE 15 LIPOXYGENASE; ARACHIDONATE 5 LIPOXYGENASE; ARACHIDONIC ACID; C REACTIVE PROTEIN; CYCLOOXYGENASE 2; DOCOSAHEXAENOIC ACID; DOCOSAPENTAENOIC ACID; FISH OIL; HLA DR ANTIGEN; ICOSAPENTAENOIC ACID; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 6; LEUKOTRIENE B4; LINOLEIC ACID; LINOLENIC ACID; LINOLEOYL COENZYME A DESATURASE; LYCOPENE; MITOGEN ACTIVATED PROTEIN KINASE; OLIVE OIL; PLACEBO; POLYUNSATURATED FATTY ACID; PROSTAGLANDIN E2; SOMATOMEDIN C RECEPTOR; SOYBEAN OIL; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; UNINDEXED DRUG; VASCULOTROPIN;

ANGIOGENESIS; APOPTOSIS; BREAST CANCER; CANCER CONTROL; CANCER GROWTH; CANCER RISK; CELL PROLIFERATION; COLORECTAL CANCER; DIET SUPPLEMENTATION; FATTY ACID METABOLISM; HUMAN; INFLAMMATION; LINSEED; LOW FAT DIET; LUNG CANCER; NEOPLASM; NONHUMAN; PANCREAS CANCER; PHASE 2 CLINICAL TRIAL (TOPIC); PROSTATE CANCER; PROTEIN EXPRESSION; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM;

EID: 84891086024     PISSN: None     EISSN: 2234943X     Source Type: Journal    
DOI: 10.3389/fonc.2013.00224     Document Type: Review

References (83)

1. Siegel R, Naishadham D, Jemal A. Cancer statistics. CA Cancer J Clin (2013) 63:11-30. doi:10.3322/caac.21166
2. Willett WC. Diet and cancer: one view at the start of the millennium. Cancer Epidemiol Biomarkers Prev (2001) 10:3-8.
3. Gerber M. N-3 fatty acids and cancers: a systematic update review of epidemiological studies. Br J Nutr (2012) 107(Suppl 2):S228-39. doi:10.1017/S0007114512001614
4. de Lorgeril M, Salen P. New insights into the health effects of dietary saturated and n-6 and n-3 polyunsaturated fatty acids. BMC Med (2012) 10:50. doi:10.1186/1741-7015-10-50
5. Wright JD, Kennedy-Stephenson J, Wang CY, McDowell MA, Johnson CL, National Center for Health Statistics CDC. Trends in intake of energy and macronutrients-United States, 1971-2000. MMWR Morb Mortal Wkly Rep (2004) 53(04):80-2.
6. Available from: www.cdc.gov/nchs/data/ad/ad348.pdf [cited 2013 May 23].
7. Astorg P. Dietary N-6 and N-3 polyunsaturated fatty acids and prostate cancer risk: a review of epidemiological and experimental evidence. Cancer Causes Control (2004) 15:367-86. doi:10.1023/B:CACO.0000027498.94238.a3
8. Berger MF, Lawrence MS, Demichelis F, Drier Y, Cibulskis K, Sivachenko AY, et al. The genomic complexity of primary human prostate cancer. Nature (2011) 470:214-20. doi:10.1038/nature09744
9. Schaeffer L, Gohlke H, Muller M, Heid IM, Palmer LJ, Kompauer I, et al. Common genetic variants of the FADS1 FADS2 gene cluster and their reconstructed haplotypes are associated with the fatty acid composition in phospholipids. Hum Mol Genet (2006) 15:1745-56. doi:10.1093/hmg/ddl117
10. Blasbalg TL, Hibbeln JR, Ramsden CE, Majchrzak SF, Rawlings RR. Changes in consumption of omega-3 and omega-6 fatty acids in the United States during the 20th century. Am J Clin Nutr (2011) 2011(93):950-62. doi:10.3945/ajcn.110.006643
11. Mathias RA, Sergeant S, Ruczinski I, Torgerson DG, Hugenschmidt CE, Kubala M, et al. The impact of FADS genetic variants on ?6 polyunsaturated fatty acid metabolism in African Americans. BMC Genet (2011) 20(12):50. doi:10.1186/1471-2156-12-50
12. Merino DM, Johnston H, Clarke S, Roke K, Nielsen D, Badawi A, et al. Polymorphisms in FADS1 and FADS2 alter desaturase activity in young Caucasian and Asian adults. Mol Genet Metab (2011) 103:171-8. doi:10.1016/j.ymgme.2011.02.012
13. Simopoulos AP. Evolutionary aspects of diet, the omega-6/omega-3 ratio and genetic variation: nutritional implications for chronic diseases. Biomed Pharmacother (2006) 60:502-7. doi:10.1016/j.biopha.2006.07.080
14. Balkwill F, Coussens LM. Cancer: an inflammatory link.Cancer: an inflammatory link. Nature (2004) 431:405-6. doi:10.1038/431405a
15. Harnack K, Andersen G, Somoza V. Quantitation of alpha-linolenic acid elongation to eicosapentaenoic and docosahexaenoic acid as affected by the ratio of n6/n3 fatty acids. Nutr Metab (2009) 6:83. doi:10.1186/1743-7075-6-8
16. Carey AM, Pramanik R, Nicholson LJ, Dew TK, Martin FL, Muir GH, et al. Ras-MEK-ERK signaling cascade regulates androgen receptor element-inducible gene transcription and DNA synthesis in prostate cancer cells. Int J Cancer (2007) 121:520-7. doi:10.1002/ijc.22715
17. Deshpande R, Mansara P, Suryavanshi S, Kaul-Ghanekar R. Alpha-linolenic acid regulates the growth of breast and cervical cancer cell lines through regulation of NO release and induction of lipid peroxidation. J Mol Biochem (2013) 2:6-17.
18. Kim JY, Park HD, Park E, Chon JW, Park YK. Growth-inhibitory and proapoptotic effects of alpha-linolenic acid on estrogen-positive breast cancer cells. Ann N Y Acad Sci (2009) 1171:190-5. doi:10.1111/j.1749-6632.2009.04897.x
19. Vecchini A, Ceccarelli V, Susta F, Caligiana P, Orvietani P, Binaglia L, et al. Dietary alpha-linolenic acid reduces COX-2 expression and induces apoptosis of hepatoma cells. J Lipid Res (2004) 45:308-16. doi:10.1194/jlr.M300396-JLR200
20. Hardman WE, Ion G. Suppression of implanted MDA-MB 231 human breast cancer growth in nude mice by dietary walnut. Nutr Cancer (2008) 60:666-74. doi:10.1080/01635580802065302
21. Hardman WE, Ion G, Akinsete JA, Witte TR. Dietary walnut suppressed mammary gland tumorigenesis in the C931 Tag mouse. Nutr Cancer (2011) 2011(63):960-70. doi:10.1080/01635581.2011.589959
22. Davis PA, Vasu VT, Gohil K, Kim H, Khan IH, Cross CE, et al. A high-fat diet containing whole walnuts (Juglans regia) reduces tumour size and growth along with plasma insulin-like growth factor 1 in the transgenic adenocarcinoma of the mouse prostate model. Br J Nutr (2012) 108:1764-72. doi:10.1017/S0007114511007288
23. Nagel JM, Brinkoetter M, Magkos F, Liu X, Chamberland JP, Shah S, et al. Dietary walnuts inhibit colorectal cancer growth in mice by suppressing angiogenesis. Nutrition (2012) 28:67-75. doi:10.1016/j.nut.2011.03.004
24. Power KA, Thompson LU. Can the combination of flaxseed and its lignans with soy and its isoflavones reduce the growth stimulatory effect of soy and its isoflavones on established breast cancer? Mol Nutr Food Res (2007) 51:845-56. doi:10.1002/mnfr.200600218
25. Serhan CN. Resolution phase of inflammation: novel endogenous anti-inflammatory and proresolving lipid mediators and pathways. Annu Rev Immunol (2007) 25:101-37. doi:10.1146/annurev.immunol.25.022106.141647
26. Umar A. Is 15-LOX-1 a tumor suppressor? J Natl Cancer Inst (2012) 104:645-7. doi:10.1093/jnci/djs192
27. Yuan H, Li MY, Ma LT, Hsin MK, Mok TS, Underwood MJ, et al. 15-Lipoxygenases and its metabolites 15(S)-HETE and 13(S)-HODE in the development of non-small cell lung cancer. Thorax (2010) 65:321-6. doi:10.1136/thx.2009.122747
28. Il Lee S, Zuo X, Shureiqi I. 15-Lipoxygenase-1 as a tumor suppressor gene in colon cancer: is the verdict in? Cancer Metastasis Rev (2011) 30:481-91. doi:10.1007/s10555-011-9321-0
29. Vaiopoulos AG, Papachroni KK, Papavassiliou AG. Colon carcinogenesis: learning from NF-kappaB and AP-1. Int J Biochem Cell Biol (2010) 42:1061-5. doi:10.1016/j.biocel.2010.03.018
30. Calder PC. Omega-3 polyunsaturated fatty acids and inflammatory processes: nutrition or pharmacology? Br J Clin Pharmacol (2013) 75:645-62. doi:10.1111/j.1365-2125.2012.04374.x
31. Wang D, Dubois RN. Eicosanoids and cancer. Nat Rev Cancer (2010) 10:181-93. doi:10.1038/nrc2809
32. Tong WG, Ding XZ, Talamonti MS, Bell RH, Adrian TE. LTB4 stimulates growth of human pancreatic cancer cells via MAPK and PI-3 kinase pathways. Biochem Biophys Res Commun (2005) 335:949-56. doi:10.1016/j.bbrc.2005.07.166
33. Rola-Pleszczynski M, Stankova J. Cytokine gene regulation by PGE(2), LTB(4) and PAF. Mediators Inflamm (1992) 1:5-8. doi:10.1155/S0962935192000024
34. Kim GY, Lee JW, Cho SH, Seo JM, Kim JH. Role of the low-affinity leukotriene B4 receptor BLT2 in VEGF-induced angiogenesis. Arterioscler Thromb Vasc Biol (2009) 29:915-20. doi:10.1161/ATVBAHA.109.185793
35. Seo JM, Park S, Kim JH. Leukotriene B4 receptor-2 promotes invasiveness and metastasis of ovarian cancer cells through signal transducer and activator of transcription 3 (STAT3)-dependent up-regulation of matrix metalloproteinase 2. J Biol Chem (2012) 287:13840-9. doi:10.1074/jbc.M111.317131
36. Lee JW, Kim GY, Kim JH. Androgen receptor is up-regulated by a BLT2-linked pathway to contribute to prostate cancer progression. Biochem Biophys Res Commun (2012) 420:428-33. doi:10.1016/j.bbrc.2012.03.012
37. Ihara A, Wada K, Yoneda M, Fujisawa N, Takahashi H, Nakajima A. Blockade of leukotriene B4 signaling pathway induces apoptosis and suppresses cell proliferation in colon cancer. J Pharmacol Sci (2007) 103:24-32. doi:10.1254/jphs.FP0060651
38. Kundu JK, Surh YJ. Emerging avenues linking inflammation and cancer. Free Radic Biol Med (2012) 52:2013-37. doi:10.1016/j.freeradbiomed.2012.02.035
39. Cathcart MC, Lysaght J, Pidgeon GP. Eicosanoid signalling pathways in the development and progression of colorectal cancer: novel approaches for prevention/intervention. Cancer Metastasis Rev (2011) 30:363-85. doi:10.1007/s10555-011-9324-x
40. Bagga D, Wang L, Farias-Eisner R, Glaspy JA, Reddy ST. Differential effects of prostaglandin derived from omega-6 and omega-3 polyunsaturated fatty acids on COX-2 expression and IL-6 secretion. Proc Natl Acad Sci U S A (2003) 100:1751-6. doi:10.1073/pnas.0334211100
41. Xia D, Wang D, Kim SH, Katoh H, DuBois RN. Prostaglandin E2 promotes intestinal tumor growth via DNA methylation. Nat Med (2012) 18:224-6. doi:10.1038/nm.2608
42. Díaz-Cruz ES, Shapiro CL, Brueggemeier RW. Cyclooxygenase inhibitors suppress aromatase expression and activity in breast cancer cells. J Clin Endocrinol Metab (2005) 90:2563-70. doi:10.1210/jc.2004-2029
43. Subbaramaiah K, Hudis C, Chang SH, Hla T, Dannenberg AJ. EP2 and EP4 receptors regulate aromatase expression in human adipocytes and breast cancer cells. J Biol Chem (2008) 283:3433-44. doi:10.1074/jbc.M705409200
44. Chang SH, Liu CH, Conway R, Han DK, Nithipatikom K, Trifan OC, et al. Role of prostaglandin E2-dependent angiogenic switch in cyclooxygenase 2-induced breast cancer progression. Proc Natl Acad Sci U S A (2004) 101:591-6. doi:10.1073/pnas.2535911100
45. Reader J, Holt D, Fulton A. Prostaglandin E2 EP receptors as therapeutic targets in breast cancer. Cancer Metastasis Rev (2011) 30:449-63. doi:10.1007/s10555-011-9303-2
46. Vo BT, Morton D Jr., Komaragiri S, Millena AC, Leath C, Khan SA. TGF-β effects on prostate cancer cell migration and invasion are mediated by PGE2 through activation of PI3K/AKT/mTOR pathway. Endocrinology (2013) 154:1768-79. doi:10.1210/en.2012-2074
47. Wang X, Klein RD. Prostaglandin E2 induces vascular endothelial growth factor secretion in prostate cancer cells through EP2 receptor-mediated cAMP pathway. Mol Carcinog (2007) 46:912-23. doi:10.1002/mc.20320
48. Hawcroft G, Volpato M, Marston G, Ingram N, Perry SL, Cockbain AJ, et al. The omega-3 polyunsaturated fatty acid eicosapentaenoic acid inhibits mouse MC-26 colorectal cancer cell liver metastasis via inhibition of PGE2-dependent cell motility. Br J Pharmacol (2012) 166:1724-37. doi:10.1111/j.1476-5381.2012.01882.x
49. Szymczak M, Murray M, Petrovic N. Modulation of angiogenesis by omega-3 polyunsaturated fatty acids is mediated by cyclooxygenases. Blood (2008) 111:3514-21. doi:10.1182/blood-2007-08-109934
50. Devchand PR, Keller H, Peters JM, Vazquez M, Gonzalez FJ, Wahli W. The PPARalpha-leukotriene B4 pathway to inflammation control. Nature (1996) 384:39-43. doi:10.1038/384039a0
51. Bachi AL, Kim FJ, Nonogaki S, Carneiro CR, Lopes JD, Jasiulionis MG, et al. Leukotriene B4 creates a favorable microenvironment for murine melanoma growth. Mol Cancer Res (2009) 7:1417-24. doi:10.1158/1541-7786.MCR-09-0038
52. El-Mesery M, Al-Gayyar M, Salem H, Darweish M, El-Mowafy A. Chemopreventive and renal protective effects for docosahexaenoic acid (DHA): implications of CRP and lipid peroxides. Cell Div (2009) 4:6. doi:10.1186/1747-1028-4-6
53. Colas S, Maheo K, Denis F, Goupille C, Hoinard C, Champeroux P, et al. Sensitization by dietary docosahexaenoic acid of rat mammary carcinoma to anthracycline: a role for tumor vascularization. Clin Cancer Res (2006) 12:5879-86. doi:10.1158/1078-0432.CCR-06-0386
54. Colas S, Paon L, Denis F, Prat M, Louisot P, Hoinard C, et al. Enhanced radiosensitivity of rat autochtonous mammary tumors by dietary docosahexaenoic acid. Int J Cancer (2004) 109:449-54. doi:10.1002/ijc.11725
55. Pelser C, Mondul AM, Hollenbeck AR, Park Y. Dietary fat, fatty acids, and risk of prostate cancer in the NIH-AARP diet and health study. Cancer Epidemiol Biomarkers Prev (2013) 22:697-707. doi:10.1158/1055-9965.EPI-12-1196-T
56. Thiébaut AC, Jiao L, Silverman DT, Cross AJ, Thompson FE, Subar AF, et al. Dietary fatty acids and pancreatic cancer in the NIH-AARP diet and health study. J Natl Cancer Inst (2009) 101:1001-11. doi:10.1093/jnci/djp168
57. Park SY, Kolonel LN, Henderson BE, Wilkens LR. Dietary fat and breast cancer in postmenopausal women according to ethnicity and hormone receptor status: the Multiethnic Cohort Study. Cancer Prev Res (2012) 5:216-28. doi:10.1158/1940-6207.CAPR-11-0260
58. Daniel CR, McCullough ML, Patel RC, Jacobs EJ, Flanders WD, Thun MJ, et al. Dietary intake of n-6 and n-3 fatty acids and risk of colorectal cancer in a prospective cohort of U.S. men and women. Cancer Epidemiol Biomarkers Prev (2009) 18:516-25. doi:10.1158/1055-9965.EPI-08-0750
59. Sczaniecka AK, Brasky TM, Lampe JW, Patterson RE, White E. Dietary intake of specific fatty acids and breast cancer risk among postmenopausal women in the VITAL cohort. Nutr Cancer (2012) 64:1131-42. doi:10.1080/01635581.2012.718033
60. Thiébaut AC, Chajès V, Gerber M, Boutron-Ruault MC, Joulin V, Lenoir G, et al. Dietary intakes of n-6 and n-3 polyunsaturated fatty acids and the risk of breast cancer. Int J Cancer (2009) 124:924-31. doi:10.1002/ijc.23980
61. Murff HJ, Shu XO, Li H, Yang G, Wu X, Cai H, et al. Dietary polyunsaturated fatty acids and breast cancer risk in Chinese women: a prospective cohort study. Int J Cancer (2011) 128:1434-41. doi:10.1002/ijc.25703
62. Murff HJ, Shu XO, Li H, Dai Q, Kallianpur A, Yang G, et al. A prospective study of dietary polyunsaturated fatty acids and colorectal cancer risk in Chinese women. Cancer Epidemiol Biomarkers Prev (2009) 18:2283-91. doi:10.1158/1055-9965.EPI-08-1196
63. 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. Int J Cancer (2011) 129:1718-29. doi:10.1002/ijc.25802
64. Available from: http://nccam.nih.gov/health/omega3/introduction.htm#use [cited 2013 May 29].
65. Cheng L, Eng C, Nieman LZ, Kapadia AS, Du XL. Trends in colorectal cancer incidence by anatomic site and disease stage in the United States from 1976 to 2005. Am J Clin Oncol (2011) 34:573-80. doi:10.1097/COC.0b013e3181fe41ed
66. Aronson WJ, Kobayashi N, Barnard RJ, Henning S, Huang M, Jardack PM, et al. Phase II prospective randomized trial of a low-fat diet with fish oil supplementation in men undergoing radical prostatectomy. Cancer Prev Res (2011) 4(12):2062-71. doi:10.1158/1940-6207.CAPR-11-0298
67. Demark-Wahnefried W, Polascik TJ, George SL, Switzer BR, Madden JF, Ruffin MT, et al. Flaxseed supplementation (not dietary fat restriction) reduces prostate cancer proliferation rates in men presurgery. Cancer Epidemiol Biomarkers Prev (2008) 17(12):3577-87. doi:10.1158/1055-9965.EPI-08-0008
68. Magbanua MJ, Roy R, Sosa EV, Weignberg V, Federman S, Mattie MD, et al. Gene expression and biological pathways in tissue of men with prostate cancer in randomized clinical trial of lycopene and fish oil supplementation. PLoS ONE (2011) 6(9): doi:10.1371/journal.pone.0024004
69. Finocchiaro C, Segre O, Fadda M, Monge T, Scigliano M, Schena M, et al. Effect of n-3 fatty acids on patients with advanced lung cancer: a double-blind, placebo-controlled study. Br J Nutr (2012) 108(2):327-33. doi:10.1017/S0007114511005551
70. van der Meij BS, Langius JAE, Smit EF, Spreeuwenberg MD, von Blomberg ME, Heijboer AC, et al. Oral nutritional supplements containing n-3 polyunsaturated fatty acids affect the nutritional status of patients with stage III non-small cell lung cancer during multimodality treatment. J Nutr (2010) 140(10):1774-80. doi:10.3945/jn.110.121202
71. Sultan J, Griffin SM, Di Franco F, Kirby JA, Shenton BK, Seal CJ, et al. Randomized clinical trial of omega-3 fatty acid-supplemented enteral nutrition versus standard enteral nutrition in patients undergoing oesophagogastric cancer surgery. Br J Surg (2012) 99:346-55. doi:10.1002/bjs.7799
72. Murphy RA, Mourtzakis M, Chu QS, Baracos VE, Reiman T, Mazurak VC. Supplementation with fish oil increases first-line chemotherapy efficacy in patients with advanced nonsmall cell lung cancer. Cancer (2011) 117(16):3774-80. doi:10.1002/cncr.25933
73. Bonatto SJ, Oliveira HH, Nunes EA, Pequito D, Iagher F, Coelho I, et al. Fish oil supplementation improves neutrophil function during cancer chemotherapy. Lipids (2012) 47(4):383-9. doi:10.1007/s11745-011-3643-0
74. van der Meij BS, Langius JAE, Spreeuwenberg MD, Slootmaker SM, Paul MA, Smit EF, et al. Oral nutritional supplements containing n-3 polyunsaturated fatty acids affect quality of life and functional status in lung cancer patients during multimodality treatment: an RCT. Eur J Clin Nutr (2012) 66:399-404. doi:10.1038/ejcn.2011.214
75. Murphy RA, Mourtzakis M, Chu QS, Baracos VE, Reiman T, Mazurak VC. Nutritional intervention with fish oil provides a benefit over standard of care for weight and skeletal muscle mass in patients with nonsmall cell lung cancer receiving chemotherapy. Cancer (2011) 117:1775-82. doi:10.1002/cncr.25709
76. Chan JM, Weinberg V, Magbanua MJ, Sosa E, Simko J, Shinohara K, et al. Nutritional supplements, COX-2 and IGF-1 expression in men on active surveillance for prostate cancer. Cancer Causes Control (2011) 22:141-50. doi:10.1007/s10552-010-9684-5
77. Azrad M, Zhang K, Vollmer RT, Madden J, Polascik TJ, Snyder DC, et al. Prostatic alpha-linolenic acid (ALA) is positively associated with aggressive prostate cancer: a relationship which may depend on genetic variation in ALA metabolism. PLoS ONE (2012) 7(12):e53104. doi:10.1371/journal.pone.0053104
78. Lane J, Mansel RE, Jiang WG. Expression of human delta-6-desaturase is associated with aggressiveness of human breast cancer. Int J Mol Med (2003) 12:253-7.
79. Nakamura MT, Nara TY. Structure, function and dietary regulation of the human delta-5, delta5 and delta9 desaturases. Annu Rev Nutr (2004) 24:345-76. doi:10.1146/annurev.nutr.24.121803.063211
80. Thiébaut AC, Kipnis V, Schatzkin A, Freedman LS. The role of dietary measurement error in investigating the hypothesized link between dietary fat intake and breast cancer-a story with twists and turns. Cancer Invest (2008) 26:68-73. doi:10.1080/07357900701527918
81. Lemaitre RN, Tanaka T, Tang W, Manichaikul A, Foy M, Kabagambe EK, et al. Genetic loc associated with plasma phospholipid n-3 fatty acids: a meta-analysis of genome-wide association studies from the CHARGE consortium. PLoS Genet (2011) 7(7):e1002193. doi:10.1371/journal.pgen.1002193
82. Tanaka T, Shen J, Abecasis GR, Kisialiou A, Ordovas JM, Guralnik JM, et al. Genome-wide association study of plasma polyunsaturated fatty acids in the InCHIANTI Study. PLoS Genet (2009) 5:e1000338. doi:10.1371/journal.pgen.1000338
83. Simopoulos AP. 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 (2010) 235:785-95. doi:10.1258/ebm.2010.009298