Coffee in Cancer Chemoprevention

Česká verzia

Authors: J. Neuwirthová; B. Gál ; P. Smilek; P. Urbánková
Authors place of work: Klinika otorinolaryngologie a chirurgie hlavy a krku LF MU a FN u sv. Anny v Brně
Published in the journal: Klin Onkol 2017; 30(2): 106-114
Category: Přehledy
doi: https://doi.org/doi: 10.14735/amko2017106

Summary

Coffee consumption is associated with a reduced risk of several diseases including cancer. Its chemopreventive effect has been studied in vitro, in animal models, and more recently in humans. Several modes of action have been proposed, namely, inhibition of oxidative stress and damage, activation of metabolizing liver enzymes involved in carcinogen detoxification processes, and anti-inflammatory effects. The antioxidant activity of coffee relies partly on its chlorogenic acid content and is increased during the roasting process. Maximum antioxidant activity is observed for medium-roasted coffee. The roasting process leads to the formation of several components, e.g., melanoidins, which have antioxidant and anti-inflammatory properties. Coffee also contains two specific diterpenes, cafestol and kahweol, which have anticarcinogenic properties. Roasted coffee is a complex mixture of various chemicals. Previous studies have reported that the chemopreventive components present in coffee induce apoptosis, inhibit growth and metastasis of tumor cells, and elicit antiangiogenic effects. A meta-analysis of epidemiological studies showed that coffee consumption is associated with a lower risk of developing various malignant tumors. This review summarizes the molecular mechanisms and the experimental and epidemiological evidence supporting the chemopreventive effect of coffee.

Key words:
coffee – chemoprevention – antioxidative enzyme – detoxification enzyme – anti-inflammatory effect

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

Submitted:
11. 9. 2016

Accepted:
24. 11. 2016

Zdroje

1. Faustmann G, Cavin CH, Nerseyan A et al. Chemopreventive properties of coffee and its constituents. In: Knasmüller S, DeMarini DM, Jihnson I et al. Chemoprevention of cancer and DNA demage by dietary factors. Wiley-VCH 2009: 579.

2. Bichler J, Cavin C, Simic T et al. Coffee consumption protects human lymphocytes against oxidative and 3-amino-1-methyl-5H-pyrido[4,3-b]indole acetate (Trp-P-2) induced DNA-damage: results of an experimental study with human volunteers. Food Chem Toxicol 2007; 45 (8): 1428–1436.

3. Bøhn SK, Blomhoff R, Paur I. Coffee and cancer risk, epidemiological evidence, and molecular mechanisms. Mol Nutr Food Res 2014; 58 (5): 915–930. doi: 10.1002/mnfr.201300526.

4. Esposito F, Morisco F, Verde V et al. Moderate coffee consumption increases plasma glutathione but not homocysteine in healthy subjects. Aliment Pharmacol Ther 2003; 17 (4): 595–601.

5. Huber WW, Scharf G, Rossmanith W et al. The coffee components kahweol and cafestol induce gamma-glutamylcysteine synthetase, the rate limiting enzyme of chemoprotective glutathione synthesis, in several organs of the rat. Arch Toxicol 2002; 75 (11–12): 685–694.

6. Hayes JD, Flanagan JU, Jowsey IR. Glutathione transferases. Annu Rev Pharmacol Toxicol 2005; 45: 51–88.

7. Richelle M, Tavazzi I, Offord E. Comparison of the antioxidant activity of commonly consumed polyphenolic beverages (coffee, cocoa, and tea) prepared per cup serving. J Agric Food Chem 201l; 49 (7): 3438–3442.

8. Moreira DP, Monteiro MC, Ribeiro-Alves M et al. Contribution of chlorogenic acids to the iron-reducing activity of coffee beverages. J Agric Food Chem 2005; 53 (5): 1399–1402.

9. Wei F, Furihata K, Koda M et al. Roasting process of coffee beans as studied by nuclear magnetic resonance: time course of changes in composition. J Agric Food Chem 2012; 60 (4): 1005–1012. doi: 10.1021/jf205315r.

10. del Castillo MD, Ames JM, Gordon MH. Effect of roasting on the antioxidant activity of coffee brews. J Agric Food Chem 2002; 50 (13): 3698–3703.

11. Paur I, Balstad TR, Blomhoff R. Degree of roasting is the main determinant of the effects of coffee on NF-kappaB and EpRE. Free Radic Biol Med 2010; 48 (9): 1218–1227. doi: 10.1016/j.freeradbiomed.2010.02.005.

12. Cavin C, Marin-Kuan M, Langouët S et al. Induction of Nrf2-mediated cellular defenses and alteration of phase I activities as mechanisms of chemoprotective effects of coffee in the liver. Food Chem Toxicol 2008; 46 (4): 1239–1248.

13. Higgins LG, Cavin C, Itoh K et al. Induction of cancer chemopreventive enzymes by coffee is mediated by transcription factor Nrf2. Evidence that the coffee-specific diterpenes cafestol and kahweol confer protection against acrolein. Toxicol Appl Pharmacol 2008; 226 (3): 328–337.

14. Juge N, Mithen RF, Traka M. Molecular basis for chemoprevention by sulforaphane: a comprehensive review. Cell Mol Life Sci 2007; 64 (9): 1105–1127.

16. Balstad TR, Carlsen H, Myhrstad MC et al. Coffee, broccoli and spices are strong inducers of electrophile response element-dependent transcription in vitro and in vivo – studies in electrophile response element transgenic mice. Mol Nutr Food Res 2011; 55 (2): 185–197. doi: 10.1002/mnfr.201000204.

17. Boettler U, Volz N, Teller N et al. Induction of antioxidative Nrf2 gene transcription by coffee in humans: depending on genotype? Mol Biol Rep 2012; 39 (6): 7155–7162. doi: 10.1007/s11033-012-1547-6.

18. Bichler J, Cavin C, Simic T et al. Coffee consumption protects human lymphocytes against oxidative and 3-amino-1-methyl-5H-pyrido[4,3-b]indole acetate (Trp-P-2) induced DNA-damage: results of an experimental study with human volunteers. Food Chem Toxicol 2007; 45 (8): 1428–1436.

19. Xu C, Li CY, Kong AN. Induction of phase I, II and III drug metabolism/transport by xenobiotics. Arch Pharm Res 2005; 28 (3): 249–268.

20. Huber WW, Parzefall W. Modification of N-acetyltransferases and glutathione S-transferases by coffee components: possible relevance for cancer risk. Methods Enzymol 2005; 401: 307–341.

21. Huber WW, Rossmanith W, Grusch M et al. Effects of coffee and its chemopreventive components kahweol and cafestol on cytochrome P450 and sulfotransferase in rat liver. Food Chem Toxicol 2008; 46 (4): 1230–1238.

22. Wattenberg LW. Inhibition of neoplasia by minor dietary constituents. Cancer Res 1983; 43 (Suppl 5): 2448s–2453s.

23. Majer BJ, Hofer E, Cavin C et al. Coffee diterpenes prevent the genotoxic effects of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and N-nitrosodimethylamine in a human derived liver cell line (HepG2). Food Chem Toxicol 2005; 43 (3): 433–441.

24. Ganmaa D, Willett WC, Li TY et al. Coffee, tea, caffeine and risk of breast cancer: a 22-year follow-up. Int J Cancer 2008; 122 (9): 2071–2076. doi: 10.1002/ijc.23336.

25. Hirose M, Nishikawa A, Shibutani M et al. Chemoprevention of heterocyclic amine-induced mammary carcinogenesis in rats. Environ Mol Mutagen 2002; 39 (2–3): 271–278.

26. Ganmaa D, Willett WC, Li TY et al. Coffee, tea, caffeine and risk of breast cancer: a 22-year follow-up. Int J Cancer 2008; 122 (9): 2071–2076. doi: 10.1002/ijc.23336.

27. Huber WW, McDaniel LP, Kaderlik KR et al. Chemoprotection against the formation of colon DNA adducts from the food-borne carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in the rat. Mutat Res 1997; 376 (1–2): 115–122.

28. Cavin C, Mace K, Offord EA et al. Protective effects of coffee diterpenes against aflatoxin B1-induced genotoxicity: mechanisms in rat and human cells. Food Chem Toxicol 2001; 39 (6): 549–556.

29. Cavin C, Bezencon C, Guignard G et al. Coffee diterpenes prevent benzo[a]pyrene genotoxicity in rat and human culture systems. Biochem Biophys Res Commun 2003; 306 (2): 488–495.

30. Miller EG, McWhorter K, Rivera-Hidalgo F et al. Kahweol and cafestol: inhibitors of hamster buccal pouch carcinogenesis. Nutr Cancer 1991; 15 (1): 41–46.

31. Yagasaki K, Miura Y, Okauchi R et al. Inhibitory effects of chlorogenic acid and its related compounds on the invasion of hepatoma cells in culture. Cytotechnology 2000; 33 (1–3): 229–235. doi: 10.1023/A: 1008141918852.

32. Shimizu M, Yoshimi N, Yamada Y et al. Suppressive effects of chlorogenic acid on N-methyl-N-nitrosourea-induced glandular stomach carcinogenesis in male F344 rats. J Toxicol Sci 1999; 24 (5): 433–439.

33. Tanaka T, Kojima T, Kawamori T et al. Inhibition of 4-nitroquinoline-1-oxide-induced rat tongue carcinogenesis by the naturally occurring plant phenolics caffeic, ellagic, chlorogenic and ferulic acids. Carcinogenesis 1993; 14 (7): 1321–1325.

34. Andersen LF, Jacobs DR Jr, Carlsen MH et al. Consumption of coffee is associated with reduced risk of death attributed to inflammatory and cardiovascular diseases in the Iowa Women‘s Health Study. Am J Clin Nutr 2006; 83 (5): 1039–1046.

35. Lopez-Garcia E, van Dam RM, Qi L et al. Coffee consumption and markers of inflammation and endothelial dysfunction in healthy and diabetic women. Am J Clin Nutr 2006; 84 (4): 888–893.

36. Kempf K, Herder C, Erlund I et al. Effects of coffee consumption on subclinical inflammation and other risk factors for type 2 diabetes: a clinical trial. Am J Clin Nutr 2010; 91 (4): 950–957. doi: 10.3945/ajcn.2009.28548.

37. Shi H, Dong L, Jiang J et al. Chlorogenic acid reduces liver inflammation and fibrosis through inhibition of toll-like receptor 4 signaling pathway. Toxicology 2013; 303: 107–114. doi: 10.1016/j.tox.2012.10.025.

38. Lee CH, Yoon SJ, Lee SM. Chlorogenic acid attenuates high mobility group box 1 (HMGB1) and enhances host defense mechanisms in murine sepsis. Mol Med 2013; 18: 1437–1448. doi: 10.2119/molmed.2012.00279.

39. Kwak SC, Lee C, Kim JY et al. Chlorogenic acid inhibits osteoclast differentiation and bone resorption by down-regulation of receptor activator of nuclear factor kappa-B ligand-induced nuclear factor of activated T cells c1 expression. Biol Pharm Bull 2013; 36 (11): 1779–1786.

40. Búfalo MC, Ferreira I, Costa G et al. Propolis and its constituent caffeic acid suppress LPS-stimulated pro-inflammatory response by blocking NF-κB and MAPK activation in macrophages. J Ethnopharmacol 2013; 149 (1): 84–92. doi: 10.1016/j.jep.2013.06.004.

41. Kim SR, Jung YR, Kim DH et al. Caffeic acid regulates LPS-induced NF-κB activation through NIK/IKK and c-Src/ERK signaling pathways in endothelial cells. Arch Pharm Res 2014; 37 (4): 539–547. doi: 10.1007/s12272-013-0211-6.

42. Chang WC, Chen CH, Lee MF et al. Chlorogenic acid attenuates adhesion molecules upregulation in IL-1 beta-treated endothelial cells. Eur J Nutr 2010; 49 (5): 267–275. doi: 10.1007/s00394-009-0083-1.

43. Chung TW, Moon SK, Chang YC et al. Novel and therapeutic effect of caffeic acid and caffeic acid phenyl ester on hepatocarcinoma cells: complete regression of hepatoma growth and metastasis by dual mechanism. FASEB J 2004; 18 (14): 1670–1681.

44. Kang CH, Jayasooriya RG, Dilshara MG et al. Caffeine suppresses lipopolysaccharide-stimulated BV2 microglial cells by suppressing Akt-mediated NF-κB activation and ERK phosphorylation. Food Chem Toxicol 2012; 50 (12): 4270–4276. doi: 10.1016/j.fct.2012.08.041.

45. Kim JY, Jung KS, Jeong HG. Suppressive effects of the kahweol and cafestol on cyclooxygenase-2 expression in macrophages. FEBS Lett 2004; 569 (1–3): 321–326.

46. Kim HG, Kim JY, Hwang YP et al. The coffee diterpene kahweol inhibits tumor necrosis factor-alpha-induced expression of cell adhesion molecules in human endothelial cells. Toxicol Appl Pharmacol 2006; 217 (3): 332–341.

47. Anton PM, Craus A, Niquet-Léridon C et al. Highly heated food rich in Maillard reaction products limit an experimental colitis in mice. Food Funct 2012; 3 (9): 941–949. doi: 10.1039/c2fo30045a.

48. Vitaglione P, Morisco F, Mazzone G et al. Coffee reduces liver damage in a rat model of steatohepatitis: the underlying mechanisms and the role of polyphenols and melanoidins. Hepatology 2010; 52 (5): 1652–1661. doi: 10.1002/hep.23902.

49. Lou Y, Peng Q, Li T et al. Cancer. Oral caffeine during voluntary exercise markedly inhibits skin carcinogenesis and decreases inflammatory cytokines in UVB-treated mice. Nutr Cancer 2013; 65 (7): 1002–1013. doi: 10.1080/01635581.2013.812224.

50. Conney AH, Lu YP, Lou YR et al. Mechanisms of Caffeine-Induced Inhibition of UVB Carcinogenesis. Front Oncol 2013; 3: 144. doi: 10.3389/fonc.2013.00144.

51. Liu JD, Song LJ, Yan DJ et al. Caffeine inhibits the growth of glioblastomas through activating the caspase-3 signaling pathway in vitro. Eur Rev Med Pharmacol Sci 2015; 19 (16): 3080–3088.

52. Oh JH, Lee JT, Yang ES et al. The coffee diterpene kahweol induces apoptosis in human leukemia U937 cells through down-regulation of Akt phosphorylation and activation of JNK. Apoptosis 2009; 14 (11): 1378–1386. doi: 10.1007/s10495-009-0407-x.

53. Um HJ, Oh JH, Kim YN et al. The coffee diterpene kahweol sensitizes TRAIL-induced apoptosis in renal carcinoma Caki cells through down-regulation of Bcl-2 and c-FLIP. Chem Biol Interact 2010; 186 (1): 36–42. doi: 10.1016/j.cbi.2010.04.013.

54. Choi DW, Lim MS, Lee JW et al. The Cytotoxicity of Kahweol in HT-29 Human Colorectal Cancer Cells Is Mediated by Apoptosis and Suppression of Heat Shock Protein 70 Expression. Biomol Ther (Seoul) 2015; 23 (2): 128–133. doi: 10.4062/biomolther.2014.133.

55. Chae JI, Jeon YJ, Shim JH. Anti-proliferative properties of kahweol in oral squamous cancer through the regulation specificity protein 1. Phytother Res 2014; 28 (12): 1879–1886. doi: 10.1002/ptr.5217.

56. Choi MJ, Park EJ, Oh JH et al. Cafestol, a coffee-specific diterpene, induces apoptosis in renal carcinoma Caki cells through down-regulation of anti-apoptotic proteins and Akt phosphorylation. Chem Biol Interact 2011; 190 (2–3): 102–108. doi: 10.1016/j.cbi.2011.02.013.

57. Kotowski U, Heiduschka G, Seemann R et al. Effect of the coffee ingredient cafestol on head and neck squamous cell carcinoma cell lines. Strahlenther Onkol 2015; 191 (6): 511–517. doi: 10.1007/s00066-014-0807-x.

58. Merighi S, Benini A, Mirandola P et al. Caffeine inhibits adenosine-induced accumulation of hypoxia-inducible factor-1alpha, vascular endothelial growth factor, and interleukin-8 expression in hypoxic human colon cancer cells. Mol Pharmacol 2007; 72 (2): 395–406.

59. Moeenfard M, Cortez A, Machado V et al. Anti-angiogenic properties of cafestol and kahweol palmitate diterpene esters. J Cell Biochem 2016; 117 (12): 2748–2756. doi: 10.1002/jcb.25573.

60. Chung TW, Moon SK, Chang YC et al. Novel and therapeutic effect of caffeic acid and caffeic acid phenyl ester on hepatocarcinoma cells: complete regression of hepatoma growth and metastasis by dual mechanism. FASEB J 2004; 18 (14): 1670–1681.

61. Kim HG, Kim JY, Hwang YP et al. The coffee diterpene kahweol inhibits tumor necrosis factor-alpha-induced expression of cell adhesion molecules in human endothelial cells. Toxicol Appl Pharmacol 2006; 217 (3): 332–341.

62. Honn KV, Tang DG, Crissman JD. Platelets and cancer metastasis: a causal relationship? Cancer Metastasis Rev 1992; 11 (3–4): 325–351.

63. Bhaskar S, Rauf AA. Modulatory effect of coffee on platelet function. Indian J Physiol Pharmacol 2010; 54 (2): 141–148.

64. Natella F, Nardini M, Belelli F et al. Effect of coffee drinking on platelets: inhibition of aggregation and phenols incorporation. Br J Nutr 2008; 100 (6): 1276–1282. doi: 10.1017/S0007114508981459.

65. Arab L. Epidemiologic evidence on coffee and cancer. Nutr Cancer 2010; 62 (3): 271–283. doi: 10.1080/01635580903407122.

66. Yu X, Bao Z, Zou J et al. Coffee consumption and risk of cancers: a meta-analysis of cohort studies. BMC Cancer 2011; 11 (1): 96. doi: 10.1186/1471-2407-11-96.

67. Bravi F, Bosetti C, Tavani A et al. Coffee reduces risk for hepatocellular carcinoma: an updated meta-analysis. Clin Gastroenterol Hepatol 2013; 11 (11): 1413–1421. doi: 10.1016/j.cgh.2013.04.039.

68. Larsson SC, Wolk A. Coffee consumption and risk of liver cancer: a meta-analysis. Gastroenterology 2007; 132 (5): 1740–1745.

69. Sang LX, Chang B, Li XH et al. Consumption of coffee associated with reduced risk of liver cancer: a meta-analysis. BMC Gastroenterol 2013; 13 (1): 34. doi: 10.1186/1471-230X-13-34.

70. Dušek L, Mužík J, Malúšková D et al. Epidemiologie zhoubných nádorů se zavedeným screeningem v mezinárodním srovnání. Klin Onkol 2014; 27 (Suppl 2): 2S40–2S48. doi: 10.14735/amko20142S40.

71. Galeone C, Turati F, La Vecchia C et al. Coffee consumption and risk of colorectal cancer: a meta-analysis of case-control studies. Cancer Causes Control 2010; 21 (11): 1949–1959. doi: 10.1007/s10552-010-9623-5.

72. Li G, Ma D, Zhang Y et al. Coffee consumption and risk of colorectal cancer: a meta-analysis of observational studies. Public Health Nutr 2013; 16 (2): 346–357. doi: 10.1017/S1368980012002601.

73. Tian C, Wang W, Hong Z et al. Coffee consumption and risk of colorectal cancer: a dose-response analysis of observational studies. Cancer Causes Control 2013; 24 (6): 1265–1268.

74. Wang ZJ, Ohnaka K, Morita M et al. Dietary polyphenols and colorectal cancer risk: the Fukuoka colorectal cancer study. World J Gastroenterol 2013; 19 (17): 2683–2690. doi: 10.3748/wjg.v19.i17.2683.

75. Crippa A, Discacciati A, Larsson SC et al. Coffee consumption and mortality from all causes, cardiovascular disease, and cancer: a dose-response meta-analysis. Am J Epidemiol 2014; 180 (8): 763–775. doi: 10.1093/aje/kwu194.

76. Groessl EJ, Allison MA, Larson JC et al. Coffee consumption and the incidence of colorectal cancer in women. J Cancer Epidemiol 2016; 2016: 6918431. doi: 10.1155/2016/6918431.

77. Guercio BJ, Sato K, Niedzwiecki D et al. coffee intake, recurrence, and mortality in stage III colon cancer: results from CALGB 89803 (Alliance). J Clin Oncol 2015; 33 (31): 3598–3607. doi: 10.1200/JCO.2015.61.5062.

78. Zheng JS, Yang J, Fu YQ et al. Effects of green tea, black tea, and coffee consumption on the risk of esophageal cancer: a systematic review and meta-analysis of observational studies. Nutr Cancer 2013; 65 (1): 1–16. doi: 10.1080/01635581.2013.741762.

79. Turati F, Galeone C, La Vecchia C et al. Coffee and cancers of the upper digestive and respiratory tracts: meta-analyses of observational studies. Ann Oncol 2011; 22 (3): 536–544. doi: 10.1093/annonc/mdq603.

80. Li YM, Peng J, Li LZ. Coffee consumption associated with reduced risk of oral cancer: a meta-analysis. Oral Surg Oral Med Oral Pathol Oral Radiol 2016; 121 (4): 381–389. doi: 10.1016/j.oooo.2015.12.006.

81. Liu J, Shen B, Shi M et al. Higher caffeinated coffee intake is associated with reduced malignant melanoma risk: a meta-analysis study. PLoS One 2016; 11 (1): e0147056. doi: 10.1371/journal.pone.0147056.

82. Vatten LJ, Solvoll K, Løken EB. Coffee consumption and the risk of brest cancer. A prospective study of 14,593 Norwegian women. Br J Cancer 1990; 62 (2): 267–270.

83. Li J, Seibold P, Chang-Claude J et al. Coffee consumption modifies risk of estrogen-receptor negative breast cancer. Breast Cancer Res 2011; 13 (3): R49. doi: 10.1186/bcr2879.

84. Nkondjock A, Ghadirian P, Kotsopoulos J et al. Coffee consumption and breast cancer risk among BRCA1 and BRCA2 mutation carriers. Int J Cancer 2006; 118 (1): 103–107.

85. Jiang W, Wu Y, Jiang X. Coffee and caffeine intake and breast cancer risk: an updated dose-response meta-analysis of 37 published studies. Gynecol Oncol 2013; 129 (3): 620–629. doi: 10.1016/j.ygyno.2013.03.014.

86. Bartoňková H, Foretová L, Helmichová E. Doporučené zásady péče o nemocné s nádory prsu a vaječníků a zdravé osoby se zárodečnými mutacemi genů BRCA1 nebo BRCA2. Klin Onkol 2003; 16 (1): 28–34.

87. Bhoo-Pathy N, Peeters PH, Uiterwaal CS et al. Coffee and tea consumption and risk of pre-and postmenopausal breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort study. Breast Cancer Res 2015; 17 (1): 15. doi: 10.1186/s13058-015-0521-3.

88. Hashibe M, Galeone C, Buys SS et al. Coffee, tea, caffeine intake, and the risk of cancer in the PLCO cohort. Br J Cancer 2015; 113 (5): 809–816. doi: 10.1038/bjc.2015.276.

89. Nagata C, Kabuto M, Shimizu H. Association of coffee, green tea, and caffeine intakes with serum concentrations of estradiol and sex hormone-binding globulin in premenopausal Japanese women. Nutr Cancer 1998; 30 (1): 21–24.

90. Wierzejska R. Coffee consumption vs. cancer risk – a review of scientific data. Rocz Panstw Zakl Hig 2015; 66 (4): 293–298.

91. Jernstrom H, Klug TL, Sepkovic DW et al. Predictors of the plasma ratio of 2-hydroxyestrone to 16-alpha-hydroxyestrone among pre-menopausal, nulliparous women from four ethnic groups. Carcinogenesis 2003; 24 (5): 991–1005.

92. Falt P, Hanousek M, Kundrátová E. Prekancerózy žaludku. Klin Onkol 2013; 26 (Suppl): S22–S28. doi: 10.14735/amko2013S22.

93. Deng W, Yang H, Wang J et al. Coffee consumption and the risk of incident gastric cancer – a meta-analysis of prospective cohort studies. Nutr Cancer 2016; 68 (1): 40–47. doi: 10.1080/01635581.2016.1115093.

94. Xie F, Wang D, Huang Z et al. Coffee consumption and risk of gastric cancer: a large updated meta-analysis of prospective studies. Nutrients 2014; 6 (9): 3734–3746. doi: 10.3390/nu6093734.

95. Abnet CC, Corley DA, Freedman ND et al. Diet and upper gastrointestinal malignancies. Gastroenterology 2015; 148 (6): 1234–1243. doi: 10.1053/j.gastro.2015.02.007.

96. MacMahon B, Yen S, Trichopoulos D et al. Coffee and cancer of the pancreas. N Engl J Med 1981; 304 (11): 630–633.

97. Coffee, tea, mate, methylxanthines and methylglyoxal. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Lyon, 27 February to 6 March 1990. IARC Monogr Eval Carcinog Risks Hum 1991; 51: 1–513.

98. Hart AR, Kennedy H, Harvey I. Pancreatic cancer: a review of the evidence on causation. Clin Gastroenterol Hepatol 2008; 6 (3): 275–282.

99. Luo J, Inoue M, Iwasaki M et al. JPHC Study Group. Green tea and coffee intake and risk of pancreatic cancer in a large-scale, population-based cohort study in Japan (JPHC study). Eur J cancor Prev 2007; 16 (6): 542–548.

100. Guertin KA, Freedman ND, Loftfield E et al. A prospective study of coffee intake and pancreatic cancer: results from the NIH-AARP Diet and Health Study. Br J Cancer 2015; 113 (7): 1081–1085. doi: 10.1038/bjc.2015. 235.

101. Lee JE, Hunter DJ, Spiegelman D et al. Intakes of coffee, tea, milk, soda and juice and renal cell cancer in a pooled analysis of 13 prospective studies. Int J Cancer 2007; 121 (10): 2246–2253.

102. Klener P. Chemoprevence nádorových onemocnění. Klin Onkol 1999; 12 (3): 78–81.