Nütrigenetik ve Kanser

Öz

Sağlıklı bir yaşamın sürdürülebilmesi için dengeli ve yeterli beslenmek elzemdir. Yapılan çalışmalar neticesinde, bulaşıcı olmayan hastalıklar ve beslenme arasındaki ilişki ortaya konulmuştur. Kanser, küresel sağlık sorunlarından biridir ve dünya çapında ikinci önde gelen ölüm nedeni olarak kabul edilir. Epidemiyolojik çalışmalarda, kanserin büyük bir kısmının yaşam tarzı ve diyet ile ilişkili olduğu saptanmıştır. Kanserin önlenmesi ve tedavi sürecindeki başarı oranının arttırılması açısından, kanser ve beslenme ilişkisinin incelenmesi önem arz etmektedir. Nütrigenetik, beslenmeyi gen düzeyinde inceler ve besinlerin genler üzerindeki etkileşimine odaklanır. Beslenmenin kanser gelişimindeki rolü ve kanserde gerçekleşen epigenetik değişiklikler, nütrigenetik ve kanser arasındaki ilişkiyi ilgi çekici kılmaktadır. Mikro besin öğeleri ve bazı biyoaktif gıda bileşenlerinin kanser üzerindeki koruyucu ve terapotik etkileri, yapılan in vivo ve in vitro çalışmalarla ortaya konulmuştur. Beslenmenin, kanser üzerindeki etkileri DNA metilasyonu, apoptoz, otofaji, gen ekspresyonundaki değişiklikler ile gözlemlenebilmektedir. Bu derlemenin amacı, nütrigenetik açıdan bazı temel mikro besin ögelerinin (A vitamini, C vitamini, D vitamini), polifenollerin (epigallokateşin-3-gallat, kurkumin, resveratrol, genistein) ve bazı makro besin ögelerinin (çoklu doymamış yağ asitleri) farklı kanser türlerinin önlemesinde ve/veya tedavisinde sahip olabileceği etki mekanizmalarını değerlendirmek ve sunmaktır.

Anahtar Kelimeler

• beslenme
• nütrigenetik
• kanser ve beslenme

Nutrigenetics and Cancer

Öz

A balanced and adequate diet is essential for a healthy life. Studies have shown a link between non-communicable diseases and nutrition. Cancer is a global health problem and is recognised as the second leading cause of death worldwide. Epidemiological studies have shown that a large proportion of cancers are related to lifestyle and diet. In order to prevent cancer and increase the success rate of treatment, it is important to investigate the relationship between cancer and diet. Nutrigenetics studies diet at the gene level and focuses on the interaction of nutrients with genes. The role of diet in cancer development and epigenetic changes in cancer make the relationship between nutrigenetics and cancer interesting. The protective and therapeutic effects of micronutrients and some bioactive food constituents on cancer have been demonstrated by in vivo and in vitro studies. Dietary effects on cancer can be observed through changes in DNA methylation, apoptosis, autophagy and gene expression. The aim of this review is to evaluate and present the mechanisms of action of some essential micronutrients (vitamin A, vitamin C, vitamin D), polyphenols (epigallocatechin-3-gallate, curcumin, resveratrol, genistein) and some macronutrients (polyunsaturated fatty acids) in the prevention and/or treatment of different types of cancer.

Anahtar Kelimeler

• nutrition
• nutrigetics
• cancer and nutrition

Kaynakça

1. Al Binali, H. H. (2014). Night blindness and ancient remedy. Heart Views: The Official Journal of the Gulf Heart Association, 15(4), 136.
2. Alizadeh, F., Bolhassani, A., Khavari, A., Bathaie, S. Z., Naji, T., & Bidgoli, S. A. (2014). Retinoids and their biological effects against cancer. International immunopharmacology, 18(1), 43-49.
3. Al Yousef, N., Shinwari, Z., Al Shahrani, B., Al Showimi, M., & Al Moghrabi, N. (2020). Curcumin induces re expression of BRCA1 and suppression of γ synuclein by modulating DNA promoter methylation in breast cancer cell lines. Oncology reports, 43(3), 827-838.
4. Andreescu, N., Puiu, M., & Niculescu, M. (2018). Effects of dietary nutrients on epigenetic changes in cancer. Cancer Epigenetics for Precision Medicine, 121-139.
5. Ardekani, A. M., & Jabbari, S. (2009). Nutrigenomics and cancer. Avicenna journal of medical biotechnology, 1(1), 9.
6. Azrad, M., Turgeon, C. E., & Demark-Wahnefried, W. (2013). Current evidence linking polyunsaturated fatty acids with cancer risk and progression. Frontiers in oncology, 3, 60076.
7. Bag, A., & Bag, N. (2018). Tea polyphenols and prevention of epigenetic aberrations in cancer. Journal of natural science, biology, and medicine, 9(1), 2.
8. Banikazemi, Z., Haji, H. A., Mohammadi, M., Taheripak, G., Iranifar, E., Poursadeghiyan, M., ... & Mirzaei, H. (2018). Diet and cancer prevention: Dietary compounds, dietary MicroRNAs, and dietary exosomes. Journal of cellular biochemistry, 119(1), 185-196

9. Bentley, R., & Haslam, E. (1990). The shikimate pathway—a metabolic tree with many branche. Critical reviews in biochemistry and molecular biology, 25(5), 307-384.
10. Berger, S. H., Pittman, D. L., & Wyatt, M. D. (2008). Uracil in DNA: consequences for carcinogenesis and chemotherapy. Biochemical pharmacology, 76(6), 697-706.
11. Bikle, D. D. (2014). Vitamin D metabolism, mechanism of action, and clinical applications. Chemistry & biology, 21(3), 319-329.
12. Braconi, C., Kogure, T., Valeri, N., Huang, N., Nuovo, G., Costinean, S., ... & Patel, T. (2011). microRNA-29 can regulate expression of the long non-coding RNA gene MEG3 in hepatocellular cancer. Oncogene, 30(47), 4750-4756.
13. Braicu, C., Mehterov, N., Vladimirov, B., Sarafian, V., Nabavi, S. M., Atanasov, A. G., & Berindan-Neagoe, I. (2017, October). Nutrigenomics in cancer: Revisiting the effects of natural compounds. In Seminars in cancer biology (Vol. 46, pp. 84-106). Academic Press.
14. Bui, A. Q., Gunathilake, M., Lee, J., Oh, J. H., Chang, H. J., Sohn, D. K., ... & Kim, J. (2023). Interaction between retinol intake and ISX rs5755368 polymorphism in colorectal cancer risk: a case–control study in a Korean population. Scientific Reports, 13(1), 10187.
15. Bull, C., & Fenech, M. (2008). Genome-health nutrigenomics and nutrigenetics: nutritional requirements or ‘nutriomes’ for chromosomal stability and telomere maintenance at the individual level: Symposium on ‘Diet and cancer’. Proceedings of the Nutrition Society, 67(2), 146-156.
16. Castilho, R. M., Squarize, C. H., & Almeida, L. O. (2017). Epigenetic modifications and head and neck cancer: implications for tumor progression and resistance to therapy. International journal of molecular sciences, 18(7), 1506.
17. Charoenngam, N., & Holick, M. F. (2020). Immunologic effects of vitamin D on human health and disease. Nutrients, 12(7), 2097. Chen, Q., Polireddy, K., Chen, P., & Dong, R. (2015). The unpaved journey of vitamin C in cancer treatment. Canadian journal of physiology and pharmacology, 93(12), 1055-1063.
18. Cheng, X., & Blumenthal, R. M. (2008). Mammalian DNA methyltransferases: a structural perspective. Structure, 16(3), 341-350.
19. Choi, E. J., Jung, J. Y., & Kim, G. H. (2014). Genistein inhibits the proliferation and differentiation of MCF-7 and 3T3-L1 cells via the regulation of ERα expression and induction of apoptosis. Experimental and therapeutic medicine, 8(2), 454-458.
20. Crew, K. D., Ho, K. A., Brown, P., Greenlee, H., Bevers, T. B., Arun, B., ... & Hershman, D. L. (2015). Effects of a green tea extract, Polyphenon E, on systemic biomarkers of growth factor signalling in women with hormone receptor‐negative breast cancer. Journal of Human Nutrition and Dietetics, 28(3), 272-282.
21. Cui, X., Jin, Y., Hofseth, A. B., Pena, E., Habiger, J., Chumanevich, A., ... & Hofseth, L. J. (2010). Resveratrol suppresses colitis and colon cancer associated with colitis. Cancer prevention research, 3(4), 549-559.
22. Çelik, F., & Köksal, G. (2013). Kanser ve Sülforafan. Beslenme ve Diyet Dergisi, 41(3), 266-273.
23. D'Addario, C., Di Francesco, A., Pucci, M., Finazzi Agrò, A., & Maccarrone, M. (2013). Epigenetic mechanisms and endocannabinoid signalling. The FEBS journal, 280(9), 1905-1917.
24. Daniel, M., & Tollefsbol, T. O. (2015). Epigenetic linkage of aging, cancer and nutrition. Journal of Experimental Biology, 218(1), 59-70.
25. Donovan, M. G., Selmin, O. I., Doetschman, T. C., & Romagnolo, D. F. (2019). Epigenetic activation of BRCA1 by genistein in vivo and triple negative breast cancer cells linked to antagonism toward aryl hydrocarbon receptor. Nutrients, 11(11), 2559.
26. Ducasse M, Brown M.A. (2006). Epigenetic aberrations and cancer. Molecular cancer, 5, 1-10.
27. Duverger, O., & Morasso, M. I. (2008). Role of homeobox genes in the patterning, specification, and differentiation of ectodermal appendages in mammals. Journal of cellular physiology, 216(2), 337-346.
28. Elsamanoudy, A. Z., Neamat-Allah, M. A. M., Mohammad, F. A. H., Hassanien, M., & Nada, H. A. (2016). The role of nutrition related genes and nutrigenetics in understanding the pathogenesis of cancer. Journal of Microscopy and Ultrastructure, 4(3), 115-122.
29. Esteller, M. (2007). Cancer epigenomics: DNA methylomes and histone-modification maps. Nature reviews genetics, 8(4), 286-298.
30. Fabbri, M., Garzon, R., Cimmino, A., Liu, Z., Zanesi, N., Callegari, E., ... & Croce, C. M. (2007). MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proceedings of the National Academy of Sciences, 104(40), 15805-15810.
31. Fang L, Robertson KD, Wolffe AP. (2007). DNA methylation in health anddisease. Nat Rev Genet, 1:11.
32. Fatemeh Rezaiian, Sayed Hossein Davoodi, Bahareh Nikooyeh et al. Vitamin D status and its relation with insulin resistance and VDR-FokI polymorphism in Iranian non-melanoma skin cancer (NMSC) patients: a case-control study, 14 June 2019, PREPRINT (Version 1) available at Research Square [https://doi.org/10.21203/rs.2.10291/v1]
33. Feil, R., & Fraga, M. F. (2012). Epigenetics and the environment: emerging patterns and implications. Nature reviews genetics, 13(2), 97-109.
34. Fenech, M. (2008). Genome health nutrigenomics and nutrigenetics–diagnosis and nutritional treatment of genome damage on an individual basis. Food and Chemical Toxicology, 46(4), 1365-1370.
35. Food, N. (2007). Physical Activity, and the Prevention of Cancer: a Global Perspective. Washington, DC.
36. Fujiki, H., Watanabe, T., Sueoka, E., Rawangkan, A., & Suganuma, M. (2018). Cancer prevention with green tea and its principal constituent, EGCG: From early investigations to current focus on human cancer stem cells. Molecules and cells, 41(2), 73.
37. Gao, Y., & Tollefsbol, T. O. (2018). Combinational proanthocyanidins and resveratrol synergistically inhibit human breast cancer cells and impact epigenetic–mediating machinery. International journal of molecular sciences, 19(8), 2204.
38. Garzon, R., Liu, S., Fabbri, M., Liu, Z., Heaphy, C. E., Callegari, E., ... & Marcucci, G. (2009). MicroRNA-29b induces global DNA hypomethylation and tumor suppressor gene reexpression in acute myeloid leukemia by targeting directly DNMT3A and 3B and indirectly DNMT1. Blood, The Journal of the American Society of Hematology, 113(25), 6411-6418.
39. Gillberg, L., Ørskov, A. D., Nasif, A., Ohtani, H., Madaj, Z., Hansen, J. W., ... & Grønbæk, K. (2019). Oral vitamin C supplementation to patients with myeloid cancer on azacitidine treatment: Normalization of plasma vitamin C induces epigenetic changes. Clinical epigenetics, 11(1), 1-11.
40. Gloria, N. F., Soares, N., Brand, C., Oliveira, F. L., Borojevic, R., & Teodoro, A. J. (2014). Lycopene and beta-carotene induce cell-cycle arrest and apoptosis in human breast cancer cell lines. Anticancer research, 34(3), 1377-1386.
41. Gomez-Casati, D. F., Zanor, M. I., & Busi, M. V. (2013). Metabolomics in plants and humans: applications in the prevention and diagnosis of diseases. BioMed research international, 2013.
42. Grimm, M., Cetindis, M., Biegner, T., Lehman, M., Munz, A., Teriete, P., & Reinert, S. (2015). Serum vitamin D levels of patients with oral squamous cell carcinoma (OSCC) and expression of vitamin D receptor in oral precancerous lesions and OSCC. Medicina oral, patologia oral y cirugia bucal, 20(2), e188.
43. Guo, Y., Wu, R., Gaspar, J. M., Sargsyan, D., Su, Z. Y., Zhang, C., ... & Kong, A. N. (2018). DNA methylome and transcriptome alterations and cancer prevention by curcumin in colitis-accelerated colon cancer in mice. Carcinogenesis, 39(5), 669-680.
44. Henning, S. M., Wang, P., Carpenter, C. L., & Heber, D. (2013). Epigenetic effects of green tea polyphenols in cancer. Epigenomics, 5(6), 729-741.
45. Herrmann, K. M. (1995). The shikimate pathway: early steps in the biosynthesis of aromatic compounds. The Plant Cell, 7(7), 907.
46. Herrmann, K. M., & Weaver, L. M. (1999). The shikimate pathway. Annual review of plant biology, 50(1), 473-503.
47. Holick, C. N., Stanford, J. L., Kwon, E. M., Ostrander, E. A., Nejentsev, S., & Peters, U. (2007). Comprehensive association analysis of the vitamin D pathway genes, VDR, CYP27B1, and CYP24A1, in prostate cancer. Cancer Epidemiology and Prevention Biomarkers, 16(10), 1990-1999.
48. Holick, M. F. (2008). Vitamin D and sunlight: strategies for cancer prevention and other health benefits. Clinical journal of the American Society of Nephrology: CJASN, 3(5), 1548.
49. Huang, C. Y., Han, Z., Li, X., Xie, H. H., & Zhu, S. S. (2017). Mechanism of EGCG promoting apoptosis of MCF-7 cell line in human breast cancer. Oncology letters, 14(3), 3623-3627.
50. Hughes, L. A., van den Brandt, P. A., De Bruïne, A. P., Wouters, K. A., Hulsmans, S., Spiertz, A., ... & van Engeland, M. (2009). Early life exposure to famine and colorectal cancer risk: a role for epigenetic mechanisms. PloS one, 4(11), e7951.
51. Hulbert, A. J., Turner, N., Storlien, L. H., & Else, P. L. (2005). Dietary fats and membrane function: implications for metabolism and disease. Biological Reviews, 80(1), 155-169. Irimie, A. I., Braicu, C., Cojocneanu-Petric, R., Berindan-Neagoe, I., & Campian, R. S. (2015). Novel technologies for oral squamous carcinoma biomarkers in diagnostics and prognostics. Acta Odontologica Scandinavica, 73(3), 161-168.
52. Irimie, A. I., Braicu, C., Pasca, S., Magdo, L., Gulei, D., Cojocneanu, R., ... & Berindan-Neagoe, I. (2019). Role of key micronutrients from nutrigenetic and nutrigenomic perspectives in cancer prevention. Medicina, 55(6), 283.
53. Issa, J. P. (2004). CpG island methylator phenotype in cancer. Nature Reviews Cancer, 4(12), 988-993.
54. Jang, Y. G., Go, R. E., Hwang, K. A., & Choi, K. C. (2019). Resveratrol inhibits DHT-induced progression of prostate cancer cell line through interfering with the AR and CXCR4 pathway. The Journal of steroid biochemistry and molecular biology, 192, 105406.
55. Kang, J. X. (2013). Nutrigenomics and cancer therapy. Lifestyle Genomics, 6(3), I-II.
56. Kazemian, E., Akbari, M. E., Moradi, N., Gharibzadeh, S., Mondul, A. M., Jamshidi-Naeini, Y., ... & Rozek, L. S. (2019). Vitamin D receptor genetic variation and cancer biomarkers among breast cancer patients supplemented with vitamin D3: a single-arm non-randomized before and after trial. Nutrients, 11(6), 1264.
57. Khan, M. A., Hussain, A., Sundaram, M. K., Alalami, U., Gunasekera, D., Ramesh, L., ... & Quraishi, U. (2015). (-)-Epigallocatechin-3-gallate reverses the expression of various tumor-suppressor genes by inhibiting DNA methyltransferases and histone deacetylases in human cervical cancer cells. Oncology reports, 33(4), 1976-1984.
58. Khan, N., & Mukhtar, H. (2015). Dietary agents for prevention and treatment of lung cancer. Cancer letters, 359(2), 155-164.
59. Komduur, R. H., Korthals, M., & Te Molder, H. (2008). The good life: living for health and a life without risks? On a prominent script of nutrigenomics. British Journal of Nutrition, 101(3), 307-316.
60. Kyle, U. G., & Pichard, C. (2006). The Dutch Famine of 1944–1945: a pathophysiological model of long-term consequences of wasting disease. Current Opinion in Clinical Nutrition & Metabolic Care, 9(4), 388-394.
61. Landis-Piwowar KR, Milacic V, Dou Q.P. (2008). Relationship between the methylation status of dietary flavonoids and their growthinhibitory and apoptosis-inducing activities in human cancer cells. J Cell Biochem 105 (2):514–523. Lee, W. J., Cheng, T. C., Yen, Y., Fang, C. L., Liao, Y. C., Kuo, C. C., ... & Ho, Y. S. (2021). Tea polyphenol epigallocatechin-3-gallate inhibits cell proliferation in a patient-derived triple-negative breast cancer xenograft mouse model via inhibition of proline-dehydrogenase-induced effects. Journal of Food and Drug Analysis, 29(1), 113.
62. Li Y, Tollefsbol T.O. (2010). Impact on DNA methylation in cancer prevention and therapy by bioactive dietary components. Curr Med Chem 17(20):2141–2151.
63. Liao, Y. P., Chen, L. Y., Huang, R. L., Su, P. H., Chan, M. W., Chang, C. C., ... & Lai, H. C. (2014). Hypomethylation signature of tumor-initiating cells predicts poor prognosis of ovarian cancer patients. Human molecular genetics, 23(7), 1894-1906.
64. Lillycrop, K. A., & Burdge, G. C. (2012). Epigenetic mechanisms linking early nutrition to long term health. Best practice & research clinical endocrinology & metabolism, 26(5), 667-676.
65. Liu, J., Shao, T., Zhang, J., Liu, Q., Hua, H., Zhang, H., ... & Jiang, Y. (2022). Gamma synuclein promotes cancer metastasis through the MKK3/6-p38MAPK cascade. International Journal of Biological Sciences, 18(8), 3167.
66. Liu, L. D., Pang, Y. X., Zhao, X. R., Li, R., Jin, C. J., Xue, J., ... & Liu, P. S. (2019). Curcumin induces apoptotic cell death and protective autophagy by inhibiting AKT/mTOR/p70S6K pathway in human ovarian cancer cells. Archives of Gynecology and Obstetrics, 299, 1627-1639.
67. Mahmoudi, Z., Jahani, M., & Nekouian, R. (2023). Role of curcumin on miR-26a and its effect on DNMT1, DNMT3b, and MEG3 expression in A549 lung cancer cell. Journal of Cancer Research and Therapeutics.
68. Maiani, G., Periago Castón, M. J., Catasta, G., Toti, E., Cambrodón, I. G., Bysted, A., ... & Schlemmer, U. (2009). Carotenoids: actual knowledge on food sources, intakes, stability and bioavailability and their protective role in humans. Molecular nutrition & food research, 53(S2), S194-S218.
69. Majid S, Kikuno N, Nelles J, Noonan E, Tanaka Y, Kawamoto K, Hirata H, Li LC, Zhao H, Okino ST, Place RF, Pookot D, Dahiya R. (2008). Genistein induces the p21WAF1/CIP1 and p16INK4a tumor suppressor genes in prostate cancer cells by epigenetic mechanisms involving active chromatin modification. Cancer Res 68(8):2736–2734.
70. Marques-Rocha, J. L., Garcia-Lacarte, M., Samblas, M., Bressan, J., Martínez, J. A., & Milagro, F. I. (2018). Regulatory roles of miR-155 and let-7b on the expression of inflammation-related genes in THP-1 cells: effects of fatty acids. Journal of physiology and biochemistry, 74, 579-589.
71. Maruti, S. S., Ulrich, C. M., & White, E. (2009). Folate and one-carbon metabolism nutrients from supplements and diet in relation to breast cancer risk. The American journal of clinical nutrition, 89(2), 624-633.
72. Mastrangelo, D., Pelosi, E., Castelli, G., Lo-Coco, F., & Testa, U. (2018). Mechanisms of anti-cancer effects of ascorbate: Cytotoxic activity and epigenetic modulation. Blood Cells, Molecules, and Diseases, 69, 57-64.
73. Meeran SM, Ahmed A, Tollefsbol T.O. (2010). Epigenetic targets of bioactive dietary components for cancer prevention and therapy. Clin Epigenetics 1(3–4):101–116.
74. Micale, V., Mazzola, C., & Drago, F. (2007). Endocannabinoids and neurodegenerative diseases. Pharmacological Research, 56(5), 382-392.
75. Mustafi, S., Camarena, V., Volmar, C. H., Huff, T. C., Sant, D. W., Brothers, S. P., ... & Wang, G. (2018). Vitamin C sensitizes melanoma to BET inhibitors. Cancer research, 78(2), 572-583.
76. Nasir, A., Bullo, M. M. H., Ahmed, Z., Imtiaz, A., Yaqoob, E., Jadoon, M., ... & Yaqoob, S. (2020). Nutrigenomics: Epigenetics and cancer prevention: A comprehensive review. Critical reviews in food science and nutrition, 60(8), 1375-1387.
77. NCBI. (2021).ISX Intestine Specific Homeobox [Homo sapiens (Human)]. https://www.ncbi.nlm.nih.gov/gene/91464.
78. Niculescu, M. D., & Lupu, D. S. (2011). Nutritional influence on epigenetics and effects on longevity. Current Opinion in Clinical Nutrition & Metabolic Care, 14(1), 35-40.
79. Notarnicola, M., Tutino, V., De Nunzio, V., Dituri, F., Caruso, M. G., & Giannelli, G. (2017). Dietary ω-3 polyunsaturated fatty acids inhibit tumor growth in transgenic ApcMin/+ mice, correlating with CB1 receptor up-regulation. International Journal of Molecular Sciences, 18(3), 485.
80. Omenn, G.S.; Goodman, G.E.; Thornquist, M.D.; Balmes, J.; Cullen, M.R.; Glass, A.; Keogh, J.P.; Meyskens, F.L., Jr.; Valanis, B.;Williams, J.H., Jr.; et al. (1996). Risk factors for lung cancer and for intervention e_ects in CARET, the Beta-Carotene and Retinol E_cacy Trial. J. Natl. Cancer Inst., 88(21), 1550–1559.
81. Ong, T. P., Moreno, F. S., & Ross, S. A. (2012). Targeting the epigenome with bioactive food components for cancer prevention. Lifestyle Genomics, 4(5), 275-292. Paluszczak J, Krajka-Kuz´niak V, Baer- Dubowska W. (2010). The effect of dietary polyphenols on the epigenetic regulation of gene expression in MCF7 breast cancer cells. Toxicol Lett 192(2):119–125.
82. Pan, P., Skaer, C. W., Stirdivant, S. M., Young, M. R., Stoner, G. D., Lechner, J. F., ... & Wang, L. S. (2015). Beneficial regulation of metabolic profiles by black raspberries in human colorectal cancer patients. Cancer Prevention Research, 8(8), 743-750.
83. Patra, S. K., & Bettuzzi, S. (2009). Epigenetic DNA-(cytosine-5-carbon) modifications: 5-aza-2′-deoxycytidine and DNA-demethylation. Biochemistry (Moscow), 74, 613-619.
84. Peluso, I., & Serafini, M. (2017). Antioxidants from black and green tea: From dietary modulation of oxidative stress to pharmacological mechanisms. British journal of pharmacology, 174(11), 1195-1208.
85. Peng, D., Ge, G., Gong, Y., Zhan, Y., He, S., Guan, B., ... & Zhou, L. (2018). Vitamin C increases 5-hydroxymethylcytosine level and inhibits the growth of bladder cancer. Clinical epigenetics, 10, 1-13.
86. Peterlik, M., Grant, W. B., & Cross, H. S. (2009). Calcium, vitamin D and cancer. Anticancer research, 29(9), 3687-3698.
87. Reimers, L. L., Crew, K. D., Bradshaw, P. T., Santella, R. M., Steck, S. E., Sirosh, I., ... & Gammon, M. D. (2015). Vitamin D-related gene polymorphisms, plasma 25-hydroxyvitamin D, and breast cancer risk. Cancer causes & control, 26, 187-203.
88. Roberts, F., Roberts, C. W., Johnson, J. J., Kyle, D. E., Krell, T., Coggins, J. R., ... & McLeod, R. (1998). Evidence for the shikimate pathway in apicomplexan parasites. Nature, 393(6687), 801-805.
89. Robertson, K. D., & Wolffe, A. P. (2000). DNA methylation in health and disease. Nature Reviews Genetics, 1(1), 11-19.
90. Ross, S. A., & Davis, C. D. (2011). MicroRNA, nutrition, and cancer prevention. Advances in nutrition, 2(6), 472-485.
91. Rothwell, J. A., Knaze, V., & Zamora-Ros, R. (2017). Polyphenols: Dietary assessment and role in the prevention of cancers. Current Opinion in Clinical Nutrition and Metabolic Care, 20(6), 512-521.
92. Saffery, R. (2014). Epigenetic change as the major mediator of fetal programming in humans: are we there yet?. Annals of Nutrition and Metabolism, 64(3-4), 203-207.
93. Sanaei, M., Kavoosi, F., Valiani, A., & Ghobadifar, M. A. (2018). Effect of genistein on apoptosis and proliferation of hepatocellular Carcinoma Hepa1-6 Cell Line. International journal of preventive medicine, 9.
94. Sarabi, M. M., & Naghibalhossaini, F. (2018). The impact of polyunsaturated fatty acids on DNA methylation and expression of DNMTs in human colorectal cancer cells. Biomedicine & Pharmacotherapy, 101, 94-99.
95. Shafiee, G., Saidijam, M., Tavilani, H., Ghasemkhani, N., & Khodadadi, I. (2016). Genistein induces apoptosis and inhibits proliferation of HT29 colon cancer cells. International journal of molecular and cellular medicine, 5(3), 178.
96. Shankar, E., J. Montellano, and S. Gupta. (2016a). Green tea polyphenols in the prevention and therapy of prostate cancer. Complementary and alternative medicines in prostate cancer: A comprehensive approach, Boca Raton, FL: CRC Press.114–24.
97. Sharma, S., Stutzman, J. D., Kelloff, G. J., & Steele, V. E. (1994). Screening of potential chemopreventive agents using biochemical markers of carcinogenesis. Cancer research, 54(22), 5848-5855.
98. Spencer, J. P., Abd El Mohsen, M. M., Minihane, A. M., & Mathers, J. C. (2008). Biomarkers of the intake of dietary polyphenols: strengths, limitations and application in nutrition research. British Journal of Nutrition, 99(1), 12-22.
99. Teegarden, D., Romieu, I., & Lelievre, S. A. (2012). Redefining the impact of nutrition on breast cancer incidence: is epigenetics involved?. Nutrition research reviews, 25(1), 68-95.
100. Theodoratou, E., Timofeeva, M., Li, X., Meng, X., & Ioannidis, J. P. (2017). Nature, nurture, and cancer risks: genetic and nutritional contributions to cancer. Annual review of nutrition, 37, 293-320.
101. Tuttis, K., Machado, A. R. T., Santos, P. W. D. S., & Antunes, L. M. G. (2023). Sulforaphane Combined with Vitamin D Induces Cytotoxicity Mediated by Oxidative Stress, DNA Damage, Autophagy, and JNK/MAPK Pathway Modulation in Human Prostate Tumor Cells. Nutrients, 15(12), 2742.
102. Ulrich, C. M. (2007). Folate and cancer prevention: a closer look at a complex picture. The American journal of clinical nutrition, 86(2), 271-273.
103. Verrax, J., & Calderon, P. B. (2008). The controversial place of vitamin C in cancer treatment. biochemical pharmacology, 76(12), 1644-1652.
104. Virtamo, J., Pietinen, P., Huttunen, J. K., Korhonen, P., Malila, N., Virtanen, M. J., ... & Albert, P. (2003). Incidence of Cancer and Mortality Following α-Tocopherol and β-Carotene Supplementation: A Postintervention Follow-up. JAMA: Journal of the American Medical Association, 290(4).
105. Wajed, S. A., Laird, P. W., & DeMeester, T. R. (2001). DNA methylation: an alternative pathway to cancer. Annals of surgery, 234(1), 10.
106. Wang, J., Dai, Y., Huang, Y., Chen, X., Wang, H., Hong, Y., ... & Cheng, B. (2013). All-trans retinoic acid restores gap junctional intercellular communication between oral cancer cells with upregulation of Cx32 and Cx43 expressions in vitro. Medicina oral, patologia oral y cirugia bucal, 18(4), e569.
107. Weng, Y. L., Liao, H. F., Li, A. F. Y., Chang, J. C., & Chiou, R. Y. Y. (2010). Oral administration of resveratrol in suppression of pulmonary metastasis of BALB/c mice challenged with CT26 colorectal adenocarcinoma cells. Molecular nutrition & food research, 54(2), 259-267.
108. Yamaji, T., Inoue, M., Sasazuki, S., Iwasaki, M., Kurahashi, N., Shimazu, T., ... & Japan Public Health Center‐based Prospective Study Group. (2008). Fruit and vegetable consumption and squamous cell carcinoma of the esophagus in Japan: the JPHC study. International journal of cancer, 123(8), 1935-1940.
109. YILMAZ, A. D. (2019). Vitamin D reseptör geni fokI polimorfizminin temporomandibular eklem dejenerasyonu ile ilişkisi. Mersin Üniversitesi Sağlık Bilimleri Dergisi, 12(1), 72-79.
110. Zeisel, S. H. (2009). Epigenetic mechanisms for nutrition determinants of later health outcomes. The American journal of clinical nutrition, 89(5), 1488S-1493S.
111. Zeljic, K., Supic, G., Stamenkovic Radak, M., Jovic, N., Kozomara, R., & Magic, Z. (2012). Vitamin D receptor, CYP27B1 and CYP24A1 genes polymorphisms association with oral cancer risk and survival. Journal of oral pathology & medicine, 41(10), 779-787.
112. Zhang, N. (2015). Epigenetic modulation of DNA methylation by nutrition and its mechanisms in animals. Animal nutrition, 1(3), 144-151.
113. Zhang, Z., Tang, H., Wang, Z., Zhang, B., Liu, W., Lu, H., ... & Li, G. (2011). MiR-185 targets the DNA methyltransferases 1 and regulates global DNA methylation in human glioma. Molecular cancer, 10(1), 1-16.
114. Zhou, H., Chen, J. X., Yang, C. S., Yang, M. Q., Deng, Y., & Wang, H. (2014). Gene regulation mediated by microRNAs in response to green tea polyphenol EGCG in mouse lung cancer. BMC genomics, 15, 1-10.
115. Zupančič, D., Korać-Prlić, J., Kreft, M. E., Franković, L., Vilović, K., Jeruc, J., ... & Terzić, J. (2020). Vitamin A rich diet diminishes early urothelial carcinogenesis by altering retinoic acid signaling. Cancers, 12(7), 1712.
116. expression of DNMTs in human colorectal cancer cells. Biomedicine & Pharmacotherapy, 101, 94-99.
117. Shafiee, G., Saidijam, M., Tavilani, H., Ghasemkhani, N., & Khodadadi, I. (2016). Genistein induces apoptosis and inhibits proliferation of HT29 colon cancer cells. International journal of molecular and cellular medicine, 5(3), 178.
118. Shankar, E., J. Montellano, and S. Gupta. (2016a). Green tea polyphenols in the prevention and therapy of prostate cancer. Complementary and alternative medicines in prostate cancer: A comprehensive approach, Boca Raton, FL: CRC Press.114–24.
119. Sharma, S., Stutzman, J. D., Kelloff, G. J., & Steele, V. E. (1994). Screening of potential chemopreventive agents using biochemical markers of carcinogenesis. Cancer research, 54(22), 5848-5855.
120. Spencer, J. P., Abd El Mohsen, M. M., Minihane, A. M., & Mathers, J. C. (2008). Biomarkers of the intake of dietary polyphenols: strengths, limitations and application in nutrition research. British Journal of Nutrition, 99(1), 12-22.
121. Teegarden, D., Romieu, I., & Lelievre, S. A. (2012). Redefining the impact of nutrition on breast cancer incidence: is epigenetics involved?. Nutrition research reviews, 25(1), 68-95.
122. Theodoratou, E., Timofeeva, M., Li, X., Meng, X., & Ioannidis, J. P. (2017). Nature, nurture, and cancer risks: genetic and nutritional contributions to cancer. Annual review of nutrition, 37, 293-320.
123. Tuttis, K., Machado, A. R. T., Santos, P. W. D. S., & Antunes, L. M. G. (2023). Sulforaphane Combined with Vitamin D Induces Cytotoxicity Mediated by Oxidative Stress, DNA Damage, Autophagy, and JNK/MAPK Pathway Modulation in Human Prostate Tumor Cells. Nutrients, 15(12), 2742.
124. Ulrich, C. M. (2007). Folate and cancer prevention: a closer look at a complex picture. The American journal of clinical nutrition, 86(2), 271-273.
125. Verrax, J., & Calderon, P. B. (2008). The controversial place of vitamin C in cancer treatment. biochemical pharmacology, 76(12), 1644-1652.
126. Virtamo, J., Pietinen, P., Huttunen, J. K., Korhonen, P., Malila, N., Virtanen, M. J., ... & Albert, P. (2003). Incidence of Cancer and Mortality Following α-Tocopherol and β-Carotene Supplementation: A Postintervention Follow-up. JAMA: Journal of the American Medical Association, 290(4).
127. Wajed, S. A., Laird, P. W., & DeMeester, T. R. (2001). DNA methylation: an alternative pathway to cancer. Annals of surgery, 234(1), 10.
128. Wang, J., Dai, Y., Huang, Y., Chen, X., Wang, H., Hong, Y., ... & Cheng, B. (2013). All-trans retinoic acid restores gap junctional intercellular communication between oral cancer cells with upregulation of Cx32 and Cx43 expressions in vitro. Medicina oral, patologia oral y cirugia bucal, 18(4), e569.
129. Weng, Y. L., Liao, H. F., Li, A. F. Y., Chang, J. C., & Chiou, R. Y. Y. (2010). Oral administration of resveratrol in suppression of pulmonary metastasis of BALB/c mice challenged with CT26 colorectal adenocarcinoma cells. Molecular nutrition & food research, 54(2), 259-267.
130. Yamaji, T., Inoue, M., Sasazuki, S., Iwasaki, M., Kurahashi, N., Shimazu, T., ... & Japan Public Health Center‐based Prospective Study Group. (2008). Fruit and vegetable consumption and squamous cell carcinoma of the esophagus in Japan: the JPHC study. International journal of cancer, 123(8), 1935-1940.
131. YILMAZ, A. D. (2019). Vitamin D reseptör geni fokI polimorfizminin temporomandibular eklem dejenerasyonu ile ilişkisi. Mersin Üniversitesi Sağlık Bilimleri Dergisi, 12(1), 72-79.
132. Zeisel, S. H. (2009). Epigenetic mechanisms for nutrition determinants of later health outcomes. The American journal of clinical nutrition, 89(5), 1488S-1493S.
133. Zeljic, K., Supic, G., Stamenkovic Radak, M., Jovic, N., Kozomara, R., & Magic, Z. (2012). Vitamin D receptor, CYP27B1 and CYP24A1 genes polymorphisms association with oral cancer risk and survival. Journal of oral pathology & medicine, 41(10), 779-787.
134. Zhang, N. (2015). Epigenetic modulation of DNA methylation by nutrition and its mechanisms in animals. Animal nutrition, 1(3), 144-151.
135. Zhang, Z., Tang, H., Wang, Z., Zhang, B., Liu, W., Lu, H., ... & Li, G. (2011). MiR-185 targets the DNA methyltransferases 1 and regulates global DNA methylation in human glioma. Molecular cancer, 10(1), 1-16.
136. Zhou, H., Chen, J. X., Yang, C. S., Yang, M. Q., Deng, Y., & Wang, H. (2014). Gene regulation mediated by microRNAs in response to green tea polyphenol EGCG in mouse lung cancer. BMC genomics, 15, 1-10.
137. Zupančič, D., Korać-Prlić, J., Kreft, M. E., Franković, L., Vilović, K., Jeruc, J., ... & Terzić, J. (2020). Vitamin A rich diet diminishes early urothelial carcinogenesis by altering retinoic acid signaling. Cancers, 12(7), 1712.