Valdés-Ramos, Roxana; Benítez-Arciniega, Alejandra D. The British Journal of Nutrition 98.S1 Gizi dan Kekebalan pada Kanker Penerjemah : Fika Shafiana Nadia G2B013007 S1 ILMU GIZI FAKULTAS ILMU KEPERAWATAN DAN KESEHATAN UNIVERSITAS MUHAMMADIYAH SEMARANG 2

  

  Gizi dan Kekebalan pada Kanker Penerjemah :

  Fika Shafiana Nadia G2B013007 S1 ILMU GIZI FAKULTAS ILMU KEPERAWATAN DAN KESEHATAN UNIVERSITAS MUHAMMADIYAH SEMARANG

  2015

  

Gizi dan Kekebalan pada Kanker

  Valdés-Ramos, Roxana; Benítez-Arciniega, Alejandra D. British Journal of Nutrition98.S1 (Oktober 2007): S127-32.

  ABSTRAK Tujuan artikel ini adalah untuk memberikan gambaran umum tentang dampak gizi pada perkembangan kanker serta sebagai bagian dari pendekatan terapi. Ada banyak bukti bahwa diet dan gaya hidup dapat mengubah risiko perkembangan kanker seperti halnya bagi banyak penyakit kronis lainnya. Ini mungkin melalui tindakan langsung pada sistem kekebalan tubuh, baik dengan meningkatkan atau menekan itu, serta pada pengembangan tumor itu sendiri, oleh modulasi ekspresi gen atau oleh aktivitas antioksidan. Efek protektif dapat dicapai dengan asupan yang memadai dari vitamin A dan C, β-karoten, selenium dan asam n-3 asam lemak antara lain, sementara efek negatif yang ditemukan terutama dengan intake tinggi n-6 dan asam lemak jenuh. Berat badan, obesitas dan kurangnya aktivitas fisik secara teratur juga telah dikaitkan dengan peningkatan risiko kanker. Efek perlindungan yang terbaik diamati ketika diet dan gaya hidup yang memadai yang hadir bersama-sama. Sehubungan dengan peran terapi gizi pada kanker, telah diamati bahwa penggunaan nutrisi enteral atau parenteral pra atau pasca operasi dapat meningkatkan tingkat kelangsungan hidup pasien dan kualitas hidup; Namun, penelitian lebih lanjut diperlukan di daerah tertentu.

  Payudara, usus besar, rektum, prostat, perut dan paru-paru adalah jenis kanker yang paling sering dikaitkan dengan diet atau komponen makanan.

  Sebuah sel kanker adalah salah satu yang telah mengubah morfologi serta fungsinya. Secara khusus ia telah kehilangan kemampuan bahwa semua sel harus mengontrol pertumbuhan mereka sendiri, baik dengan apoptosis atau dengan mengurangi tingkat reproduksi mereka. Mutasi dan mengakibatkan perubahan morfologi sel terjadi di seluruh individu hidup-waktu. Sebuah sistem kekebalan tubuh yang utuh harus dapat menghancurkan sel-sel kanker segera setelah mereka muncul. Kanker sebagai penyakit muncul ketika sistem kekebalan tubuh tidak mampu mempertahankan pengawasan organisme.

  Hubungan antara gizi dan kanker adalah bi-directional dan sangat kompleks. Komponen makanan telah ditemukan untuk menginduksi perubahan mutagenik atau, sebaliknya, untuk melindungi terhadap faktor mutagenik atau untuk meningkatkan efisiensi sistem kekebalan tubuh. Setelah proses kanker telah dimulai dalam individu, pangan dan gizi dapat menghasilkan efek penting pada pertumbuhan atau involusi tumor.

  Awal kanker. Kanker biasanya penyakit usia tua dan peningkatan harapan hidup di sebagian besar negara, dan khususnya di yang maju, jelas meningkatkan kejadian sebagian besar jenis cancers1. Pola penyakit tidak sepenuhnya dijelaskan oleh faktor risiko yang diketahui. Banyak kemajuan telah dibuat dalam memahami dasar molekuler dari karsinogenesis, terutama konsensus dekat yang timbul hampir semua kanker dari akumulasi mutasi genetik dan pengakuan yang lebih baru dari peran peradangan dan lingkungan mikro jaringan, khususnya untuk kanker tergantung hormon . Namun, mutasi paling genetik yang berkontribusi terhadap kanker tidak diwariskan, dan dengan demikian harus disebabkan akumulasi mutasi somatik dan perubahan epigenetik, dari faktor lingkungan belum kurang dipahami, yang pasti tidak dapat dijelaskan sepenuhnya oleh tembakau, menggunakan dan timbul selama kursus seumur hidup 2. Pemeliharaan normal setiap organisme berarti bahwa sel-sel mereplikasi dengan pembagian untuk menggantikan sel-sel tua dan memperbaiki daerah jaringan yang rusak. Pembelahan sel dimulai dengan replikasi DNA, yang berlangsung seumur hidup manusia normal sekitar 1.016 kali. Meskipun sistem replikasi DNA sangat akurat, peluang untuk terjadi kesalahan dan ini dapat menyebabkan mutasi. Selain kesalahan yang terjadi selama replikasi DNA yang normal, paparan beberapa agen kimia atau radiasi, serta infeksi virus, dapat menyebabkan perubahan lebih lanjut dalam DNA. 1

  Kanker dapat berkembang ketika sel terakumulasi mutasi pada gen yang berhubungan dengan pertumbuhan sel dan kelangsungan hidup. Gen-gen ini adalah baik proto-onkogen yang biasanya membantu memulai dan melaksanakan pembelahan sel atau supresor tumor gen yang mencegah proliferasi sel mutan. Akumulasi mutasi muncul dengan penuaan canggih tubuh dan jika sistem kekebalan tubuh tidak mampu mengidentifikasi dan menghancurkan sel-sel bermutasi.

  Sel kanker mereplikasi pada tingkat yang lebih tinggi dari sel normal, sehingga meningkatkan kemungkinan mutasi lebih lanjut, dan beberapa sel yang rusak dapat bermigrasi ke jaringan lain, menyebabkan metastasis atau pertumbuhan tumor dalam jaringan lain dari yang asal. Semakin lama kanker diperbolehkan untuk terus tumbuh, semakin sedikit kemungkinan sistem kekebalan tubuh untuk dapat mengenali sel yang rusak dan menghancurkan mereka. Ketika sel-sel bermutasi beberapa, sistem kekebalan tubuh dapat mengenali dan melanjutkan untuk menghancurkan mereka karena akan infeksi bakteri atau virus. Namun ketika kanker tumbuh, sel-sel yang rusak yang berbeda mungkin begitu banyak bahwa sistem ini mampu menghancurkan mereka semua dan gagal dalam pekerjaan pengawasan yang 1.

  Studi pada hewan telah menunjukkan bahwa penyesuaian epigenetik dan metabolisme yang disebabkan oleh modifikasi di lingkungan gizi selama tahap- tahap embrionik atau janin pembangunan mungkin memiliki efek penting pada genetika kanker di antara penyakit kronis lainnya. Interaksi antara polimorfisme nukleotida tunggal dalam berbagai gen telah dikaitkan dengan respon metabolik untuk diet mempengaruhi perkembangan penyakit kronis seperti obesitas, penyakit jantung dan kanker. Warisan genetik memungkinkan individu untuk mengembangkan salah satu dari beberapa fenotipe yang ditentukan oleh kondisi metabolik dan lingkungan, seperti gizi 3-5.

  Salah satu asosiasi yang paling dievaluasi secara menyeluruh antara nutrisi dan sistem kekebalan tubuh yang berkaitan dengan diet lemak. Meskipun asupan adalah jenis lemak yang memiliki efek yang lebih penting pada respon kekebalan tubuh dan akibatnya pada perkembangan kanker 6,7. Asam lemak tak jenuh ganda (PUFA) telah ditunjukkan untuk memodulasi produksi sitokin, proliferasi limfosit, ekspresi molekul permukaan, fagositosis, apoptosis dan aktivitas sel pembunuh alami; dua efek terakhir terkait erat dengan perkembangan kanker. Peningkatan n

• 3 PUFA membantu mengontrol produksi eikosanoid proinflamasi serta sitokin production8. Telah terbukti secara in vitro bahwa asam palmitat mampu mempotensiasi keracunan besi-dimediasi sel endotel, menyebabkan disfungsi mitokondria, kematian sel, apoptosis, dan mutation9-14 DNA.

  Peran gizi dalam perkembangan kanker

  Sistem kekebalan tubuh, ketika bertindak sebagai pertahanan utama tubuh terhadap patogen dan sel-sel kanker, menggunakan sitokin pro-inflamasi, serta oksigen dan nitrogen spesies reaktif. Ketika produksi zat ini adalah berlebihan dapat menyebabkan peradangan kronis dan peningkatan risiko kanker, peradangan telah dikaitkan dengan fase promosi karsinogenesis, dengan menghambat sel untuk komunikasi sel antara sel normal dan kanker terpengaruh. Dalam hal ini, kemampuan organisme untuk serangan balik efek ini sangat penting untuk menghentikan produksi sel-sel kanker. Nutrisi seperti seng, selenium, vitamin A dan C, n -3 PUFA dan probiotik memodulasi respon imun atau bertindak sebagai antioksidan, membantu sistem kekebalan tubuh untuk bekerja secara khusus terhadap sel kanker dan tidak melawan cells15,16 berdekatan normal.

  Apoptosis atau kematian sel terprogram adalah mekanisme yang paling penting untuk pemeliharaan jaringan normal dan organ. Sel kanker yang telah kehilangan kemampuan untuk menyeimbangkan proliferasi sel. Banyak komponen makanan dapat bertindak sebagai agen kemopreventif, berinteraksi pada tingkat molekuler dan seluler untuk memodulasi apoptosis, melalui selektif mengaktifkan atau menonaktifkan ekspresi gen. Meskipun banyak penelitian terbaru telah difokuskan pada identifikasi efek spesifik nutrisi tunggal atau komponen makanan pada ekspresi gen, perlu diingat bahwa individu mengkonsumsi kombinasi nutrisi dalam makanan dalam diet, dan bahwa interaksi komponen ini mungkin tidak memiliki efek positif atau negatif yang sama. Pemahaman yang lebih baik dari interaksi ini dapat membantu mengidentifikasi kombinasi ideal makanan untuk pencegahan kanker. Rendah serat dan tinggi asupan daging merah, serta ketidakseimbangan n -3 dan n -6 asam lemak telah dikaitkan dengan peningkatan risk17-19 kanker. Komponen makanan dapat mengubah ekspresi gen dan fenotip sel melalui berbagai langkah, sehingga mempengaruhi cancer20-24.

  Studi epidemiologi telah menunjukkan bahwa 30 sampai 40% dari semua kanker dapat dicegah dengan mempertahankan gaya hidup sehat dan diet yang memadai. Meningkatkan asupan buah dan sayuran dapat menurunkan risiko kanker, terutama payudara, usus besar, rektum, prostat dan paru-paru 25,26. Efek ini mungkin karena penurunan sehingga asupan lemak total dan melalui peningkatan vitamin dan mineral seperti selenium, asam folat, vitamin B12, vitamin D, antioksidan seperti karotenoid (alpha-carotene, beta-karoten, likopen, lutein , cryptoxanthin), serta phytochemical (senyawa fenolik, terpenoid, steroid, indoles dan serat) dan pra dan probiotik 22,27-30.

  Misalnya, telah menunjukkan bahwa asupan selenium dalam dosis farmakologis (> atau = 200 [mu] g / hari) dapat melindungi terhadap prostat, usus, dan paru-paru cancers31. Metabolisme besi juga telah dikaitkan dengan kanker payudara dan usus besar cancer32-35. Vitamin E selain terkenal fungsi anti- oksidan, memodulasi aktivitas enzim mikrosomal, menghambat protein kinase C dan menginduksi apoptosis, sehingga bertindak atas pertumbuhan tumor dan proliferation36-40 seluler. Vitamin D memiliki efek antiproliferatif, mempromosikan diferensiasi selular mirip dengan proses neoplasic; juga telah dikaitkan untuk protection41 UV-radiasi.

  

Tabel 1 menyajikan daftar nutrisi yang telah dikaitkan dengan perkembangan

  berbagai jenis kanker baik dengan meningkatkan sistem kekebalan tubuh atau dengan mengerahkan efek imunosupresif. Itu selalu penting untuk dicatat bahwa meskipun beberapa dari efek ini telah diamati dengan penggunaan suplemen, sebagian besar dari mereka terkait dengan asupan makanan yang mengandung ini nutrients.

  Table 1 Komponen makanan terkait dengan perkembangan kanker atau pencegahan

  Peran berat dalam risiko kanker Sebagai konsekuensi dari yang berlebihan dan sebagian besar tidak seimbang asupan makanan, serta gaya hidup menetap, kelebihan berat badan dan obesitas meningkat di seluruh dunia, sehingga meningkatkan risiko untuk semua penyakit kronis, termasuk kanker. Bahkan, masalah berat badan terkait juga telah dikaitkan dengan pengembangan berbagai jenis kanker 42. Ada banyak bukti yang menunjukkan bahwa kelebihan berat badan merupakan faktor risiko untuk pengembangan dan prognosis dari beberapa jenis kanker termasuk kanker usus besar, payudara, endometrium, ginjal dan esofagus, serta mungkin sites43-45 tambahan. Misalnya, kanker prostat telah berhubungan dengan BMI yang lebih tinggi dan berat dewasa gain, sementara payudara, ovarium dan kanker endometrium telah ditemukan terkait dengan kelebihan berat badan dan berat badan di life45,46 dewasa. Penurunan berat badan setelah menopause dikaitkan dengan risiko substansial mengurangi kanker payudara, sehingga menunjukkan bahwa akuisisi dan pemeliharaan berat badan yang sesuai atau BMI sepanjang masa dewasa juga dapat mengakibatkan pengurangan penting dari risk47-50 kanker.

  Peran gizi dalam terapi kanker

  Sebagian besar penelitian yang telah dilakukan di bidang gizi dan kanker berhubungan dengan mengidentifikasi penyebab dan cara mencegah timbulnya peristiwa neoplasic. Namun, penelitian juga telah dilakukan pada penggunaan nutrisi untuk meningkatkan hasil pasien setelah perawatan bedah tumor. n -3 asam lemak, arginin, dan nukleotida untuk formula dinyatakan gizi lengkap. Ada beberapa uji coba menunjukkan bahwa imunonutrisi pra-operasi meningkatkan hasil pada pasien dengan gastrointestinal (GI) operasi kanker atas dan hemat biaya, komplikasi berkurang 50-52.

  Pra-operasi imunonutrisi dapat menyebabkan perubahan yang memodulasi respons stres dan meningkatkan hasil pasien yang menjalani operasi kanker perut. Imunonutrisi enteral pra-operasi pada pasien dengan kanker GI meningkatkan status gizi dan kekebalan dan mengurangi timbulnya komplikasi pasca operasi dan infeksi, oleh modulasi reaksi inflamasi. Imunonutrisi pra-operasi telah disarankan untuk memperbaiki gangguan keseimbangan Th1 / Th2 yang ditemukan pada kanker 53-57.

  Sebuah pra-operasi rumus khusus lisan dengan arginin, n -3 asam lemak, dan RNA telah terbukti sama efektifnya dengan pemberian pra dan pasca-operasi dari imunonutrisi dalam menurunkan kejadian infeksi pasca operasi dan lama tinggal di rumah sakit. Nutrisi enteral pra-operasi telah disarankan untuk memberikan regulasi yang lebih baik dari pemulihan sistem kekebalan tubuh pasca-operasi dari nutrisi parenteral. Di sisi lain, awal nutrisi enteral pasca-operasi dilengkapi dengan arginin, omega-3 asam lemak dan RNA telah terbukti meningkatkan sintesis hidroksiprolin dan meningkatkan penyembuhan luka operasi pada pasien yang menjalani gastrektomi untuk kanker 58-60.

  Kesimpulan

  Ada banyak literatur yang menunjukkan bahwa diet dan beberapa komponen gizi dapat membantu mencegah perkembangan kanker dalam jangka panjang. Hal ini penting bagi penyedia layanan kesehatan untuk kedua mengakui dan menerapkan prinsip-prinsip gizi untuk pencegahan kanker, dan sebagai bagian dari rejimen terapi untuk meningkatkan prognosis setelah kanker telah didiagnosis. Sehubungan dengan pencegahan, pilihan terbaik adalah untuk mempertahankan gaya hidup sehat, mengikuti rekomendasi umum dari World Cancer Research Fund / American Institute for Cancer Research 1997 laporan 61, yang telah diringkas dalam Tabel 2. Sayangnya, meskipun banyak penelitian telah dilakukan sejak rekomendasi ini diterbitkan, tidak ada pedoman resmi telah dipublikasikan sejak saat itu. Untuk yang terbaik dari pengetahuan kita, WCRF / AICR berencana untuk menerbitkan laporan baru mereka pada November 2007. Namun, sampai telah dirilis ada rekomendasi lain dapat dibuat. Sehubungan dengan efek terapi gizi pada kanker, banyak pekerjaan yang diperlukan karena ada beberapa studi yang benar-benar longitudinal untuk menyelidiki ini 60 .

  Table 2. World Cancer Research Fund / Institut Amerika untuk Penelitian Kanker 1997 Pedoman untuk Pencegahan Kanker Dunia

  Dari: World Cancer Research Fund / American Institute of Cancer Diet Penelitian, Nutrisi dan Pencegahan Kanker Manusia: Sebuah Perspektif Global London, WCRF, 199.761.

  Kemajuan dalam analisis dan pemahaman urutan DNA, RNA transkrip dan metabolisme melalui genomik, proteomik dan metabolomik, kemungkinan mungkin berkembang menjadi profil metabolik yang akan menyebabkan terapi diet individual untuk kanker dan penyakit kronis lainnya 62. Gambar. 1 menunjukkan cara yang mungkin di mana gizi dapat memiliki efek pada perkembangan kanker sama sekali stages.Fig. 1 Kemungkinan efek nutrisi pada tahap perkembangan kanker (Diadaptasi dari ref.1 Parham P (2005)).

  References 1 P Parham (2005) Cancer and interactions with the immune system.

  Manipulation of the immune response. In The Immune System, 2nd ed., pp. 412- 430 New York: Garland Science.

  2 D Davis, M Donovan, R Herberman, M Gaynor, D Axelrod, N Van Larebeke & R Sasco, The need to develop centers for environmental oncology. doi 101016/ jbiopha.2007.06.006.

  3 PJ Stover & C Garza (2006) Nutrition and developmental biology - implications for public health. Nut Rev 64, 5 Pt 2, S60-S71.10.1301/nr.2006.may.S60-S71

  4 IR Ferguson (2006) Nutrigenomics: integrating genomic approaches into nutrition research. Mol Diagn Ther 10, 101-108.16669608

  5 WN Lee & VL Go (2005) Nutrient-gene interactions: tracer-based metabolomics. J Nutr 132, Suppl 12, 3027S-3032S.

  6 MA De Pablo, MA Puertollano & G Alvarez de Cienfuegos (2002) Biological and clinical significance of lipids as modulators of immune system functions. Clin. Diagn. Lab Immunol. 9, 945-950.10.1128/CDLI.9.5.945-950.200212204942

  7 S Granados, JL Quiles, A Gil & MC Ramírez-Tortosa (2006) Dietary lipids and cancer. Nutr Hosp 21, suppl 2, 44-54.

  8 B Sweeney, P Puri & DJ Reen (2005) Modulation of immune cell function by polyunsaturated fatty acids. Pediatr Surg Int 21, 335-340.10.1007/s00383-005- 1385-x15834730

  9 D Yao, W Shi, Y Gou, X Zhou, T Yee-Aw, Y Zhou & Z Liu (2005) Fatty acid- mediated intracellular iron translocation: a synergistic mechanism of oxidative injury. Free Radic Biol Med 39, 1305-1310.10.1016/ j.freeradbiomed.2005.07.01516257639

  10 MA Azevedo, A Monteiro, C Lima, S Lenzen & R Curi (2006) Fatty acid- induced toxicity and neutral lipid accumulation in insulin-producing RINm5F

  11 S Srivastava & C Chan (2007) Hydrogen peroxide and hydroxyl radicals mediate palmitate-induced cytotoxicity to hepatoma cells: relation to mithocondrial permeability transition. Free Radic Res 41(1), 38- 49.10.1080/1071576060094390017164177

  12 N Borradaile, X Han, J Harp, S Gale, D Ory & J Schaffer (2006) Disruption of endoplasmic reticulum structure and integrity in lipotoxic cell death. J Lipid Res 47(12), 2726-2737.10.1194/jlr.M600299-JLR20016960261

  13 A Busch, E Guriski, D Cordery, M Sudlow, G Denver, D Laybutt, W Hughes & T Biden (2005) Increased fatty acid desaturation and enhanced expression of stearoyl coenzyme A desaturase protects pancreatic beta-cells from lipoapoptosis.

  Diabetes 54(10), 2917-2924.10.2337/diabetes.54.10.291716186393

  14 B Atshaver, S Storey, A Petrescu, C Greenberg, O Lyuksvutova, R Smith & F Schroeder (2002) Expression of fatty acid binding proteins inhibits lipid accumulation and alters toxicity in L cell fibrobalsts. Am J Physiol Cell Physiol.

  283(3), C688-C703.12176726 15 M Philpott & LR Ferguson (2004) Immunonutrition and cancer. Mutat Res. 551, 29-42.15225579

  16 JE Trosko (2006) Dietary modulation of the multistage, multimechanisms of human carcinogenesis: effects on initiated stem cells and cell-cell communication. Nutr Cancer 54, 102-110.10.1207/s15327914nc5401_1216800778

  17 I Beruin, Y Min, R Wu, J Wu, D Perry, J Cline, M Thomas, T Thornburg, G Kulik, A Smith, I Edwarrds, R D'Agostino, H Zhang, H Wu, J Kang & Y Chen (2007) Modulation of prostate cancer genetic risk by omega-3 and omega-6 fatty acids. J Clin Invest. 117(7), 1866-1875.10.1172/JCI3149417607361

  18 J Chavarro, M Stampfer, H Li, H Campos, T Kurth & J Ma (2007) A prospective study of polyunsaturated fatty acid levels in blood and prostate cancer risk. Cancer Epidemiol Biomarkers Prev. 16(17), 1364-1370.10.1158/1055- 9965.EPI-06-103317585059

  19 L Neuhouser, J Barnett, A Kristal, C Ambrosone, I King, M Thornquist & G Goodman (2007) (n-6) PUFA increase and dairy foods decrease prostate cancer risk in heavy smokers. J Nutr. 137(7), 1821-1827.17585037

  20 CD Davis & SA Ross (2007) Dietary components impact histone modifications and cancer risk. Nutr Rev. 65, 88-94.10.1301/nr.2007.aug.S71- S7417345961

  21 CD Davis (2007) Nutritional interactions: credentialing of molecular targets for cancer prevention. Exp Biol Med 232, 176-183.

  22 D Divisi, S Di Tommaso, S Salvemini, M Garramone & R Crisci (2006) Diet and cancer. Acta Biomed. 77, 118-123.17172193

  23 N Khan, F Afaq & H Mukhtar (2007) Apoptosis by dietary factors: the suicide solution for delaying cancer growth. Carcinogenesis 28, 233-239, Epub 2006 Dec 6.10.1093/carcin/bgl24317151090

  24 KR Martin (2006) Targeting apoptosis with dietary bioactive agents. Exp Biol Med 231, 117-129.

  25 E Theodoratou, G McNeill, R Cetnarskyj, S Farrington, A Tenesa, R Barnetson, M Porteous, M Dunlop & H Campbell (2007) Dietary fatty acids and colorectal cancer: a case-control study. Am J Epidemiol 166(2), 181-195.10.1093/ aje/kwm06317493949

  26 Y Kimura, S Kono, K Toyomura, J Nagano, T Mizoue, MA Moore, R Mibu, M Tanaka, Y Kakeji, Y Maehara, T Okamura, K Ikejiri, K Futami, Y Yasunami, T Maekawa, K Takenaka, H Ichimiya & N Imaizumi (2007) Meat, fish and fat intake in relation to subsite-specific risk of colorectal cancer: The Fukuoka Colorectal Cancer Study. Cancer Sci 98(4), 590-597.10.1111/j.1349- 7006.2007.00425.x17425596

  27 E Fernandez, S Gallus & C La Vecchia (2006) Nutrition and cancer risk: an overview. J Br Menopause Soc 12, 139- 142.10.1258/13621800677916048117178013

  28 CA Gonzalez (2006) Nutrition and cancer: the current epidemiological evidence. Br J Nutr 91, Suppl 1, 42S-45S.

  29 H Vainio & E Weiderpass (2006) Fruit and vegetables in cancer prevention. Nutr Cancer 54, 111-142.10.1207/s15327914nc5401_1316800779

  30 H Nishino, M Murakoshi, XY Mou, S Wada, M Masuda, Y Ohsaka, Y Satomi & K Jinno (2005) Cancer prevention by phytochemicals. Oncology 69, Suppl 1,

  38S-40S, Epub 2005 Sep 19.10.1159/000086631

  31 Y Cui, S Vogt, N Olson, A Glass & T Rohan (2007) Levels of zinc, selenium, calcium, and iron in benign breast tissue and risk of subsequent breast cancer. Cancer Epidemiol Biomarkers Prev. 16(8), 1682-1685.10.1158/1055-9965.EPI- 07-018717684146

  32 D Raje, H Mukhtar, A Oshowo & C Ingham Clark (2007) What proportion of cancer? Dis Colon Rectum. 50(8), 1211-1214.10.1007/s10350-007-0249- y17587088

  33 G Kabat, A Miller, M Jain & T Rohan (2007) Dietary iron and heme iron intake and risk of breast cancer: a prospective cohort study. Cancer Epidemiol Biomarkers Prev. 16(6), 1306-1308.10.1158/1055-9965.EPI-07-008617548704

  34 Y Knöbel, A Weise, M Glei, W Sendt, U Claussen & B Pool-Zobel (2007) Ferric iron is genotoxic in non-transformed and preneoplastic human colon cells. Food Chem Toxicol 45(5), 804-811.10.1016/j.fct.2006.10.02817157427

  35 K Hance, C Rogers, S Hursting & J Greiner (2007) Combination of physical activity, nutrition, or other metabolic factors and vaccine response. Front Biosci. 12, 4997-5029.10.2741/244417569626

  36 SJ Weinstein, ME Wright, KA Lawson, K Snyder, S Männistö, PR Taylor, J Virtamo & D Albanes (2007) Serum and dietary vitamin E in relation to prostate cancer risk. Cancer Epidemiol Biomarkers Prev. 16(6), 1253-1259.10.1158/1055- 9965.EPI-06-108417548693

  37 ME Wright, SJ Weinstein, KA Lawson, D Albanes, AF Subar, LB Dixon, T Mouw, A Schatzkin & MF Leitzmann (2007) Supplemental and dietary vitamin E intakes and risk of prostate cancer in a large prospective study. Cancer Epidemiol Biomarkers Prev. 16(6), 1128-1135.10.1158/1055-9965.EPI-06-107117548674

  38 J Guz, T Dziaman & A Szpila (2007) Do antioxidant vitamins influence carcinogenesis? Postepy Hig Med Dosw (Online) 61, 185-198.17507866

  39 P Greenwald (2007) A favorable view: progress in cancer prevention and screening. Recent Results Cancer Res. 174, 3-17.

  40 S Flora (2007) Role of free radicals and antioxidants in health and disease. Cell Mol Biol. 53(1), 1-2.

  41 G Mullin & A Dobs (2007) Vitamin D and its role in cancer and immunity: a prescription for sunlight. Nutr Clin Pract. 22(3), 305-322.17507731

  42 M Ceschi, F Gutzwiller, H Moch, M Eichholzer & NM Probst-Hensch (2007) Epidemiology and pathophysiology of obesity as cause of cancer. Swiss Med Wkly. 137, 50-56.17299670

  43 ME Wright, SC Chang, A Schatzkin, D Albanes, V Kipnis, T Mouw, P Hurwitz, A Hollenbeck & MF Leitzmann (2007) Prospective study of adiposity and weight change in relation to prostate cancer incidence and mortality. Cancer 109, 675-684.10.1002/cncr.2244317211863

  44 E Linos, MD Holmes & WC Willett (2007) Diet and breast cancer. Curr Oncol Rep. 9, 31-41.17164045

  45 AR Carmichael (2006) Obesity and prognosis of breast cancer. Obes Rev. 7, 333-340.10.1111/j.1467-789X.2006.00261.x17038127

  46 D Han, J Nie, MR Bonner, SE McCann, P Muti, M Trevisan, FA Ramirez- Marrero, D Vito & JL Freudenheim (2006) Lifetime adult weight gain, central adiposity, and the risk of pre- and postmenopausal breast cancer in the Western New York exposures and breast cancer study. Int J Cancer. 119, 2931- 2937.10.1002/ijc.2223617016824

  47 C Samanic, WH Chow, G Gridley, B Jarvholm & JF Fraumeni Jr (2006) Relation of body mass index to cancer risk in 362,552 Swedish men. Cancer Causes Control. 17, 901-909.10.1007/s10552-006-0023-916841257

  48 JB Greer, F Modugno, RB Ness & GO Allen (2006) Anthropometry and the risk of epithelial ovarian cancer. Cancer 106, 2247-2257.10.1002/ cncr.2183016596653

  49 A Trentham-Dietz, HB Nichols, JM Hampton & PA Newcomb (2006) Weight change and risk of endometrial cancer. Int J Epidemiol 35, 151-158, Epub 2005 Nov 8.10.1093/ije/dyi22616278243

  50 KC McCowen & BR Bistrian (2003) Immunonutrition: problematic or problem solving? Am J Clin Nutr 77, 764-770.12663270

  51 HC Sax (2005) Immunonutrition and upper gastrointestinal surgery: what really matters. Nutr Clin Pract. 20, 540-543.16207695

  52 A Malik, F Afaq, S Sarfaraz, VM Adhami, DN Syed & H Mukhtar (2005) Pomegranate fruit juice for chemoprevention and chemotherapy of prostate cancer. Proc Natl Acad Sci USA 102, 14813-14818, Epub 2005 Sep 28.10.1073/ pnas.050587010216192356

  53 T Tsujinaka, M Hirao, K Fujitani, H Mishima, M Ikenaga, T Sawamura & M Kurata (2007) Effect of preoperative immunonutrition on body composition in patients undergoing abdominal cancer surgery. Surg Today 37, 118-121, Epub 2007 Jan 25.10.1007/s00595-006-3332-417243029

  54 J Xu, Y Zhong, D Jing & Z Wu (2006) Preoperative enteral immunonutrition improves post-operative outcome in patients with gastrointestinal cancer. World J Surg 30, 1284-1289.10.1007/s00268-005-0756-8

  55 DW Chen, Z Wei Fei, YC Zhang, JM Ou & J Xu (2005) Role of enteral immunonutrition in patients with gastric carcinoma undergoing major surgery. Asian J Surg. 28, 121-124.15851366

  56 A Matsuda, K Furukawa, H Takasaki, H Suzuki, H Kan, H Tsuruta, S Shinji & T Tajiri (2006) Preoperative oral immune-enhancing nutritional supplementation corrects TH1/TH2 imbalance in patients undergoing elective surgery for colorectal cancer. Dis Colon Rectum. 49, 507-516.10.1007/s10350-005-0292- 516421661

  57 DN Moskovitz & YI Kim (2004) Does perioperative immunonutrition reduce postoperative complications in patients with gastrointestinal cancer undergoing operations? Nutr Rev. 62, 443-447.10.1301/nr.2004.nov.443-44715622717

  58 E Ates, S Yilmaz, S Erkasap, E Ihtiyar, Y Kaya, T Pehlivan, Z Ustuner, B Yasar & H Kiper (2004) Perioperative immunonutrition ameliorates the postoperative immune depression in patients with gastrointestinal system cancer (prospective clinical study in 42 patients). Acta Gastroenterol Belg. 67, 250- 254.15587331

  59 N Farreras, V Artigas, D Cardona, X Rius, M Trias & JA Gonzalez (2005) Effect of early postoperative enteral immunonutrition on wound healing in patients undergoing surgery for gastric cancer. Clin Nutr. 24, 55-65.10.1016/ j.clnu.2004.07.00215681102

  60 K Sanford (2005) Reintroduction to nutrition and cancer treatment. Semin Oncol Nurs. 21, 164-172.10.1016/j.soncn.2005.04.00416092803

  61 World Cancer Research Fund/American Institute of Cancer Research Diet (1997) Nutrition and Prevention of Human Cancer. A Global Perspective London: WCRF.

  62 VL Go, CT Nguyen, DM Harris & WN Lee (2005) Nutrient-gene interaction: metabolic genotype-phenotype relationship. J Nutr 132, Suppl 12, 3016S-3020S. AuthorAffiliation Facultad de Medicina, Universidad Autónoma del Estado de México, Jesús Carranza esq. Paseo Tollocan, Col. Moderna de la Cruz, Toluca, Estado de México, 50180, Mexico

  JURNAL ASLI ProQuest :

Nutrition and immunity in cancer

  

ct 2007): S127-32.

  

Abstract

  The purpose of this article is to give a general overview of the effects of

nutrition on the development of cancer as well as part of a therapeutic approach.

There is much evidence that diet and lifestyle can alter the risk of cancer development as is the case for many other chronic diseases. This may be through a direct action on the immune system, either by enhancing or suppressing it, as well as on the development of the tumour itself, by modulating gene expression or by antioxidant activity. Protective effects can be achieved by adequate intakes of vitamins A and C, β-carotene, selenium and n-3 fatty acids among others, while negative effects are found mainly with high intakes of n-6 and saturated fatty acids. Weight gain, obesity and lack of regular physical activity have also been associated with an increased risk of cancer . The protective effects are best observed when adequate diet and lifestyle are present together. With respect to the therapeutic role of nutrition in cancer , it has been observed that the use of pre- or post-operative enteral or parenteral nutrition may improve patients' survival rates and quality of life; however, more research is needed in this particular area. Breast, colon, rectum, prostate, stomach and lung are the types of cancer most commonly associated with diet or dietary components.

  A cancerous cell is one which has changed its morphology as well as its function. In particular it has lost the ability that all cells have to control their own growth, either by apoptosis or by decreasing their reproduction rate. Mutations and resulting changes in cell morphology occur throughout an individual's life- time. An intact immune system should be able to destroy cancer cells as soon as they appear. Cancer as a disease appears when the immune system is not capable of maintaining the organism's surveillance.

  The association between nutrition and cancer is bi-directional and very complex. Components of foods have been found to induce mutagenic changes or, conversely, to protect against mutagenic factors or to improve the efficiency of the immune system. Once a cancerous process has started in an individual, food and

  

nutrition may exert an important effect on the growth or involution of the tumour.

  The beginnings of cancer Cancer is typically a disease of old age and the increase in life expectancy

  in most countries, and particularly in developed ones, is clearly increasing the

  1

  incidence of most types of cancers . Patterns of the disease are not fully explained by known risk factors. Much progress has been made in understanding the molecular basis of carcinogenesis, particularly the near consensus that virtually all

  

cancers arise from an accumulation of genetic mutations and the more recent recognition of the role of inflammation and the tissue microenvironment, in particular for hormone-dependant cancers . However, most genetic mutations that contribute to cancer are not inherited, and thus must be attributable to accumulation of somatic mutations and epigenetic changes, from as yet poorly understood environmental factors, that certainly cannot be explained entirely by

  2

  tobacco, use and arise over the course of a lifetime . Normal maintenance of any organism means that cells replicate by division to replace old cells and repair any damaged tissue areas. Cell division starts with DNA replication, which takes place

  16

  in a normal human's lifetime approximately 10 times. Even though the DNA replication system is extremely accurate, opportunities for errors occur and these may cause mutations. In addition to errors occurring during normal DNA replication, exposure to some chemical agents or radiation, as well as viral

  1 infections, may induce further changes in DNA.

  Cancer may develop when a cell accumulates mutations in genes related to

  cell multiplication and survival. These genes are either proto-oncogenes that normally help initiate and execute cell division or tumour suppressor genes that prevent mutant cell proliferation. The accumulation of mutations appears with advanced ageing of the body and if the immune system is incapable of identifying and destroying the mutated cells.

  Cancerous cells replicate at a higher rate than normal cells, thus increasing the likelihood of further mutations, and some of the damaged cells may migrate to other tissues, causing metastasis or tumour growth in a tissue other than the one of origin. The longer a cancer is allowed to continue growing, the fewer the possibilities for the immune system to be able to recognise the damaged cells and destroy them. When mutated cells are few, the immune system may recognise and proceed to destroy them as it would any bacterial or viral infection. However when a cancer grows, the different damaged cells may be so many that the system

  1 is incapable of destroying them all and it fails in its surveillance job .

  Studies in animals have shown that epigenetic and metabolic adjustments caused by modifications in the nutritional environment during embryonic or foetal stages of development may have important effects on the genetics of cancer among other chronic diseases. Interactions between single nucleotide polymorphisms in various genes have been associated with metabolic responses to diet influencing the development of chronic diseases such as obesity, cardiovascular disease and cancer . Genetic inheritance allows individuals to develop any one of multiple phenotypes that are determined by metabolic and

  3-5 environmental conditions, such as nutrition .

  One of the most thoroughly evaluated associations between nutrition and the immune system is that related to dietary fat. Although total fat intake has been found to increase the risk of various types of cancer , it is the type of fat that has a more important effect on the immune response and consequently on cancer

  6,7 modulate cytokine production, lymphocyte proliferation, expression of surface molecules, phagocytosis, apoptosis and natural killer cell activity; these last two effects are closely related to cancer development. An increase in n -3 PUFAs helps control the production of proinflammatory eicosanoids as well as cytokine

  8

  production . It has been shown in vitro that palmitic acid is able to potentiate iron-mediated toxicity in endothelial cells, causing mitochondrial dysfunction, cell

  9-14 death, apoptosis, and DNA mutation .

  The role of nutrition in cancer development

  The immune system, when acting as the body's primary defence against pathogens and cancer cells, utilises pro-inflammatory cytokines, as well as reactive oxygen and nitrogen species. When the production of these substances is excessive it may lead to chronic inflammation and an increased risk of cancer , as inflammation has been linked to the promotion phase of carcinogenesis, by inhibiting cell to cell communication between normal and cancer affected cells. In this case, the organism's ability to counter-attack this effect is very important to stop the production of cancerous cells. Nutrients such as zinc, selenium, vitamins A and C, n -3 PUFAs and probiotics modulate the immune response or act as antioxidants, helping the immune system to work specifically against the

  15,16 cancerous cell and not against normal adjacent cells .

  Apoptosis or programmed cell death is the most important mechanism for the maintenance of normal tissues and organs. Cells that are cancerous have lost this ability to balance cell proliferation. Many dietary components may act as chemopreventive agents, interacting at the molecular and cellular level to modulate apoptosis, through selectively activating or inactivating gene expression. Although much of the recent research has been focused on identifying the specific effects of single nutrients or dietary components on gene expression, it is necessary to remember that the individual consumes a combination of nutrients within foods in the diet, and that the interaction of these components may not have the same positive or negative effect. A better understanding of these interactions may help identify the ideal combination of foods for cancer prevention. Low fibre and high red meat intakes, as well as an imbalance of n -3

  17-19 and n -6 fatty acids have been associated with an increase in cancer risk .

  Dietary components can alter gene expression and phenotypes of cells through

  20-24 various steps, thus influencing cancer .

  Epidemiologic studies have shown that 30 to 40 % of all cancers may be preventable by maintaining a healthy lifestyle and adequate diet. Increasing fruit and vegetable intake may lower the risk of cancer , particularly breast, colon,

  25,26

  rectum, prostate and lung . This effect may be due to a resulting decrease in total fat intake and through an increase in vitamins and minerals such as selenium, folic acid, vitamin B12, vitamin D, antioxidants such as carotenoids (alpha- carotene, beta-carotene, lycopene, lutein, cryptoxanthin), as well as phytochemicals (phenolic compounds, terpenoids, steroids, indoles and fibres)

  22,27-30 and pre- and probiotics .

  For instance, it has been shown that intake of selenium in pharmacological doses ( > or = 200 [mu]g/day) may be protective against prostate, colon, and lung

  31 32-35 cancers . Iron metabolism has also been associated to breast and colon cancer

  . Vitamin E in addition to its well known anti-oxidant functions, modulates the activity of microsomal enzymes, inhibits protein kinase C and induces apoptosis,

  36-40

  thus acting on tumour growth and cellular proliferation . Vitamin D has antiproliferative effects, promoting cellular differentiation similar to neoplasic

  41 processes; it has also been associated to UV-radiation protection .

  

Table 1 presents a list of nutrients that have been associated with the development

  of different types of cancers either by enhancing the immune system or by exerting an immunosuppressive effect. It is always important to note that although some of these effects have been observed with the use of supplements, most of them are related to the intake of the foods that contain these nutrients.Table 1

  Dietary components associated with cancer development or prevention The role of weight in cancer risk

  As a consequence of excessive and mostly unbalanced food intakes, as well as sedentary lifestyles, overweight and obesity are increasing worldwide, thus increasing the risk for all chronic diseases, including cancer . In fact, weight related issues have also been associated with the development of various types of

  42

cancer . There is much evidence suggesting that excess body weight is a risk

  factor for development and prognosis of several cancer types including cancer of the colon, breast, endometrium, kidney and oesophagus, as well as possible

  43-45

  additional sites . For instance, prostate cancer has been related to higher BMI and adult weight gain, while breast, ovarian and endometrial cancers have been

  45,46 found to be associated with excess weight and weight gain in adult life .

  Weight loss after menopause is associated with a substantially reduced risk of breast cancer , thus suggesting that acquisition and maintenance of appropriate weight or BMI throughout adulthood may well result in an important reduction of

  47-50 cancer risk .

  The role of nutrition in cancer therapy

  Most of the research that has been done in the area of nutrition and cancer is related to identifying the causes and ways of preventing the onset of a neoplasic event. However, research has also been done on the use of nutrition to improve the outcome of a patient after surgical treatment of a tumour. Enhancing immunity through diet is generally done by adding n -3 fatty acids, arginine, and nucleotides to an otherwise nutritionally complete formula. There are several trials suggesting gastrointestinal (GI) cancer surgery and is cost-effective, as complications are

  50-52 reduced .

  Pre-operative immunonutrition may induce changes that modulate stress responses and improve the outcome of patients undergoing abdominal cancer surgery. Pre-operative enteral immunonutrition in patients with GI cancer improves nutritional status and immunity and decreases the incidence of post- operative complications and infections, by modulating inflammatory reactions. Pre-operative immunonutrition has been suggested to correct the impaired Th1/

  53-57 Th2 balance found in cancer .

  A specialised pre-operative oral formula with arginine, n -3 fatty acids, and RNA has been shown to be as effective as pre- and post-operative administration of immunonutrition in decreasing the incidence of post-operative infections and length of hospital stay. Pre-operative enteral nutrition has been suggested to provide better regulation of post-operative immune system restoration than parenteral nutrition . On the other hand, early post-operative enteral nutrition supplemented with arginine, omega-3 fatty acids and RNA has been proven to increase hydroxyproline synthesis and improve surgical wound

  58-60 healing in patients undergoing gastrectomy for cancer .

  Conclusions

  There is much literature showing that diet and some nutritional components may help prevent the development of cancer in the long term. It is critical for health care providers to both acknowledge and apply the principles of nutrition for

  

cancer prevention, and as part of a therapeutic regimen to improve prognosis once

cancer has been diagnosed. With respect to prevention, the best option is to

  maintain a healthy lifestyle, following the general recommendations of the World

  61 Cancer Research Fund/American Institute for Cancer Research 1997 report ,

  which have been summarised in Table 2. Unfortunately, although much research has been undertaken since these recommendations were issued, no official guidelines have been published since then. To the best of our knowledge, the WCRF/AICR are planning to issue their new report in November 2007. However, until it has been released no other recommendations can be made. With respect to the therapeutic effects of nutrition on cancer , much work is needed as there are

  60

  few truly longitudinal studies to investigate these .Table 2 World Cancer Research Fund/American Institute for Cancer Research 1997 Guidelines for the Prevention of Global Cancer From: World Cancer Research Fund/American Institute of Cancer Research Diet,

  

Nutrition and Prevention of Human Cancer : A Global Perspective London,

  The advances in the analysis and understanding of DNA sequences, RNA transcripts and metabolism through genomics, proteomics and metabolomics, will most probably allow the identification of specific geno- and phenotypes, and possibly evolve into metabolic profiling that will lead to individualised dietary

  62

  therapies for cancer and other chronic diseases . Fig. 1 shows the possible ways in which nutrition may have an effect on cancer development at all stages.Fig. 1 Possible effects of nutrition on cancer developmental stages (Adapted from ref.1 Parham P (2005)).