Lifestyle modifications and colorectal cancer

Current Colorectal Cancer Reports

Volumn 10, Issue 1, 2014, Pages 45-54

  Durko, Lukasz ^a   Malecka Panas, Ewa ^a  

^a MEDICAL UNIVERSITY OF LODZ   (Poland)

Author keywords

Colorectal cancer; Lifestyle modification; Obesity; Physical activity; Phytochemicals; Prevention

Indexed keywords

PLANT MEDICINAL PRODUCT;

ALCOHOL CONSUMPTION; ARTICLE; CANCER INCIDENCE; CANCER RISK; COLON CARCINOGENESIS; COLORECTAL CANCER; DIETARY FIBER; DIETARY INTAKE; FRUIT; GRAIN; HUMAN; INDUSTRIALIZATION; LIFESTYLE MODIFICATION; OBESITY; PHYSICAL ACTIVITY; RED MEAT; SLEEP DEPRIVATION; TOBACCO; VEGETABLE;

EID: 84896543427     PISSN: 15563790     EISSN: 15563804     Source Type: Journal    
DOI: 10.1007/s11888-013-0203-4     Document Type: Article

References (100)

1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127(12):2893-917.
2. Bretthauer M. Evidence for colorectal cancer screening. Best Pract Res Clin Gastroenterol. 2010;24:417-25.
3. Huxley RR, Ansary-Moghaddam A, Clifton P, Czernichow S, Parr CL, Woodward M. The impact of dietary and lifestyle risk factors on risk of colorectal cancer: a quantitative overview of the epidemiological evidence. Int J Cancer. 2009;125:171-80.
4. Center MM, Jemal A, Ward E. International trends in colorectal cancer incidence rates. Cancer Epidemiol Biomarkers Prev. 2009;18:1688-94.
5. Gingras D, Beliveau R. Colorectal cancer prevention through dietary and lifestyle modifications. Cancer Microenviron. 2011;4(2):133-9.
6. Slomka M, Kaczka A, Malecka-Panas E. Environmental factors and the risk of colorectal adenomas and cancer. Clin Exp Med Lett. 2008;49(2):77-81.
7. Derry MM, Raina K, Agarwal C, Agarwal R. Identifying molecular targets of lifestyle modifications in colon cancer prevention. Front Oncol. 2013;3:119.
8. Burkitt DP. Related disease - related cause? Lancet. 1969;2:1229-31.
9. Scharlau D, Borowicki A, Habermann N, et al. Mechanisms of primary cancer prevention by butyrate and other products formed during gut flora-mediated fermentation of dietary fibre. Mutat Res. 2009;682:39-53.
10. Vergara-Castaneda HA, Guevara-Gonzalez RG, Ramos-Gomez M, Reynoso-Camacho R, Guzman-Maldonado H, Feregrino-Perez AA, et al. Non-digestible fraction of cooked bean (Phaseolus vulgaris L.) cultivar Bayo Madero suppresses colonic aberrant crypt foci in azoxymethane-induced rats. Food Funct. 2010;1:294-300.
11. Reddy BS, Hirose Y, Cohen LA, Simi B, Cooma I, Rao CV. Preventive potential of wheat bran fractions against experimental colon carcinogenesis: implications for human colon cancer prevention. Cancer Res. 2000;60:4792-7.
12. Kaczmarczyk MM, Miller MJ, Freund GG. The health benefits of dietary fiber: beyond the usual suspects of type 2 diabetesmellitus, cardiovascular disease and colon cancer. Metab Clin Exp. 2012;61:1058-66.
13. Feregrino-Perez AA, Berumen LC, Garcia-Alcocer G, Guevara-Gonzalez RG, Ramos-Gomez M, Reynoso-Camacho R, et al. Composition and chemopreventive effect of polysaccharides from common beans (Phaseolus vulgaris L.) on azoxymethane-induced colon cancer. J Agric Food Chem. 2008;56:8737-44.
14. Howe GR, Benito E, Castelleto R, et al. Dietary intake of fiber and decreased risk of cancers of the colon and rectum: evidence from the combined analysis of 13 case-control studies. J Natl Cancer Inst. 1992;84:1887-96. (Pubitemid 23004616)
15. Willett WC, Stampfer MJ, Colditz GA, et al. Relation of meat, fat, and fiber intake to the risk of colon cancer in a prospective study among women. N Engl J Med. 1990;323:1664-72.
16. Fuchs CS, Giovannucci EL, Colditz GA, et al. Dietary fiber and the risk of colorectal cancer and adenoma in women. N Engl J Med. 1999;340:169-76. (Pubitemid 29063212)
17. Surh YJ. Cancer chemoprevention with dietary phytochemicals. Nat Rev Cancer. 2003;3:768-80.
18. Krebs-Smith SM, Kantor LS. Choose a variety of fruits and vegetables daily: understanding the complexities. J Nutr. 2001;131:487S-501S. (Pubitemid 32115353)
19. Johnston CS, Taylor CA, Hampl JS. More Americans are eating "5 a day" but intakes of dark green and cruciferous vegetables remain low. J Nutr. 2000;130:3063-7. (Pubitemid 32005341)
20. Bingham SA, Day NE, Luben R, et al. Dietary fibre in food and protection against colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC): an observational study. Lancet. 2003;361:1496-501. (Pubitemid 36566339)
21. van Duijnhoven FJ, Bueno-De-Mesquita HB, Ferrari P, et al. Fruit, vegetables, and colorectal cancer risk: the European Prospective Investigation into Cancer and Nutrition. Am J Clin Nutr. 2009;89:1441-52.
22. Powers HJ. Interaction among folate, riboflavin, genotype, and cancer, with reference to colorectal and cervical cancer. J Nutr. 2005;135:2960S-6S. (Pubitemid 43156573)
23. Wang TP, Hsu SH, Feng HC, Huang RF. Folate deprivation enhances invasiveness of human colon cancer cells mediated by activation of sonic hedgehog signaling through promoter hypomethylation and cross action with transcription nuclear factor-kappa B pathway. Carcinogenesis. 2012;33(6):1158-68.
24. Giovannucci E. Epidemiologic studies of folate and colorectal neoplasia: a review. J Nutr. 2002;132:2350S-5S. (Pubitemid 34848106)
25. Cole BF, Baron JA, Sandler RS, et al. Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. JAMA. 2007;297:2351-9. (Pubitemid 46883748)
26. Mason JB, Kim SJ. Am J Gastroenterol. 2010;105:1914-6.
27. Majumdar AP, Kodali U, Jaszewski R. Chemopreventive role of folic acid in colorectal cancer. Front Biosci. 2004;9:2725-32.
28. Larsson SC, Orsini N, Wolk A. Vitamin B6 and risk of colorectal cancer. A meta-analysis of prospective studies. JAMA. 2010;303:1077-83.
29. Daniel CR, Cross AJ, Koebnick C, Sinha R. Trends in meat consumption in the USA. Public Health Nutr. 2011;14:575-83.
30. .•• Chan DS, Lau R, Aune D, Vieira R, Greenwood DC, Kampman E, et al. Red and processed meat and colorectal cancer incidence: meta-analysis of prospective studies. PLoS ONE. 2011;6:e20456. The article is a meta-analysis of 24 prospective cohort studies conducted in the USA, in ten European countries as part of EPIC, and in Finland, Sweden, the Netherlands, Japan, Australia, China, and Singapore. The data presented provide very strong evidence that " the risk increase in colorectal cancer estimated in linear dose-response models was 14% for every 100 g/day increase of total red and processed meats, 25% in colon cancer, and 31% in rectal cancer." The authors suggest that limiting red meat consumption could be a primary preventive measure in CRC..
31. Ishikawa S, Tamaki S, Ohata M, Arihara K, Itoh M. Heme induces DNA damage and hyperproliferation of colonic epithelial cells via hydrogen peroxide produced by heme oxygenase: a possible mechanism of heme-induced colon cancer. Mol Nutr Food Res. 2010;54:1182-91.
32. Knobel Y, Weise A, Glei M, Sendt W, Claussen U, Pool-Zobel BL. Ferric iron is genotoxic in non-transformed and pre-neoplastic human colon cells. Food Chem Toxicol. 2007;45:804-11. (Pubitemid 46452878)
33. O'Callaghan NJ, Toden S, Bird AR, Topping DL, Fenech M, Conlon MA. Colonocyte telomere shortening is greater with dietary red meat than white meat and is attenuated by resistant starch. Clin Nutr. 2012;31:60-4.
34. Biasi F, Mascia C, Poli G. The contribution of animal fat oxidation products to colon carcinogenesis, through modulation of TGF-β1 signaling. Carcinogenesis. 2008;29:890-4. (Pubitemid 351982231)
35. Sugimura T, Wakabayashi K, Nakagama H, Nagao M. Heterocyclic amines: mutagens/carcinogens produced during cooking of meat and fish. Cancer Sci. 2004;95:290-9. (Pubitemid 38519467)
36. Martinez ME, Jacobs ET, Ashbeck EL, et al. Meat intake, preparation methods, mutagens and colorectal adenoma recurrence. Carcinogenesis. 2007;28:2019-27. (Pubitemid 47500618)
37. Velmurugan B, Gangar SC, Kaur M, Tyagi A, Deep G, Agarwal R. Silibinin exerts sustained growth suppressive effect against human colon carcinoma SW480 xenograft by targeting multiple signaling molecules. Pharm Res. 2010;27:2085-97.
38. Derry M, Raina K, Agarwal R, Agarwal C. Differential effects of grape seed extract against human colorectal cancer cell lines: the intricate role of death receptors and mitochondria. Cancer Lett. 2013;334:69-78.
39. Rajamanickam S, Agarwal R. Natural products and colon cancer: current status and future prospects. Drug Dev Res. 2008;69:460-71.
40. Kaur M, Velmurugan B, Tyagi A, Agarwal C, Singh RP, Agarwal R. Silibinin suppresses growth of human colorectal carcinoma SW480 cells in culture and xenograft through down-regulation of beta-catenin-dependent signaling. Neoplasia. 2010;12:415-24.
41. Kauntz H, Bousserouel S, Gosse F, Raul F. The flavonolignin silibinin potentiates TRAIL-induced apoptosis in human colon adenocarcinoma and in derived TRAIL-resistant metastatic cells. Apoptosis. 2012;17:797-809.
42. Raina K, Agarwal C, Agarwal R. Effect of silibinin in human colorectal cancer cells: targeting the activation of NF-κB signaling. Mol Carcinog. 2013;52:195-206.
43. Hoh C, Boocock D, Marczylo T, Singh R, Berry DP, Dennison AR, et al. Pilot study of oral silibinin, a putative chemopreventive agent, in colorectal cancer patients: silibinin levels in plasma, colorectum, and liver and their pharmacodynamics consequences. Clin Cancer Res. 2006;12:2944-50.
44. Hatcher H, Planalp R, Cho J, Torti FM, Torti SV. Curcumin: from ancient medicine to current clinical trials. Cell Mol Life Sci. 2008;65:1631-52.
45. .• Shehzad A, Wahid F, Lee YS. Curcumin in cancer chemoprevention: molecular targets, pharmacokinetics, bioavailability, and clinical trials. Arch Pharm. 2010;343(9):489-99. Curcumin is a phenolic extract of the spice turmeric (Curcuma longa) with chemopreventive potential. The article presents recent data regarding the molecular background on the interaction curcumin with numerous signaling pathways. Additionally, the authors describe promising results of early-phase clinical trials of this substance in the treatment of neoplasms (multiple myeloma, pancreatic cancer, and colon cancer).
46. Ye SF, Hou ZQ, Zhong LM, Zhang QQ. Effect of curcumin on the induction of glutathione S-transferases and NADP(H):quinone oxidoreductase and its possible mechanism of action. Yao Xue Xue Bao. 2007;42:376-80.
47. Yogosawa S, Yamada Y, Yasuda S, Sun Q, Takizawa K, Sakai T. Dehydrozingerone, a structural analogue of curcumin, induces cell-cycle arrest at the G2/M phase and accumulates intracellular ROS in HT-29 human colon cancer cells. J Nat Prod. 2012;75:2088-93.
48. Camacho-Barquero L, Villegas I, Sanchez-Calvo JM, Talero E, Sanchez-Fidalgo S, Motilva V, et al. Curcumin, a Curcuma longa constituent, acts on MAPK p38 pathway modulating COX-2 and iNOS expression in chronic experimental colitis. Int Immunopharmacol. 2007;7:333-42. (Pubitemid 46186172)
49. Tu SP, Jin H, Shi JD, Zhu LM, Suo Y, Lu G, et al. Curcumin induces the differentiation ofmyeloid-derived suppressor cells and inhibits their interaction with cancer cells and related tumor growth. Cancer Prev Res (Phila). 2012;5:205-15.
50. Chen C, Liu Y, Chen Y, Xu J. C086, a novel analog of curcumin, induces growth inhibition and down-regulation of NFκB in colon cancer cells and xenograft tumors. Cancer Biol Ther. 2011;12:797-807.
51. Giladi N, Kazanov D, Shpitz B, Aroch I, Kraus S, Arber N. Curcumin potentiates the pro-apoptotic effects of sulindac sulfone in colorectal cancer. Expert Opin Investig Drugs. 2010;19 Suppl 1: S117-24.
52. Aroch I, Kraus S, Naumov I, et al. Chemopreventive effects of Coltect, a novel dietary supplement, alone and in combination with 5-aminosalicylic acid in 1,2-dimethylhydrazine-induced colon cancer in rats. Ther Adv Gastroenterol. 2010;3(5):281-9.
53. Yang CS, Wang X, Lu G, Picinich SC. Cancer prevention by tea: animal studies, molecular mechanisms and human relevance. Nat Rev Cancer. 2009;9:429-39.
54. Roy S, Yu Y, Padhye SB, Sarkar FH, Majumdar AP, et al. Difluorinated-curcumin (CDF) restores PTEN expression in colon cancer cells by down-regulating miR-21. PLoS One. 2013. doi:10.1371/journal.pone.0068543.
55. Patel BB, Gupta D, Elliot AA, Sengupta V, Yu Y, Majumdar AP. Curcumin targets FOLFOX-surviving colon cancer cells via inhibition of EGFRs and IGF-1R. Anticancer Res. 2010;30(2):319-25.
56. Khan N, Mukhtar H. Multitargeted therapy of cancer by green tea polyphenols. Cancer Lett. 2008;269:269-80.
57. Larsen CA, Dashwood RH. (-)-Epigallocatechin-3-gallate inhibits Met-signaling, proliferation, and invasiveness in human colon cancer cells. Arch Biochem Biophys. 2010;501:52-7.
58. Thakur VS, Ruhul Amin AR, Paul RK, Gupta K, Hastak K, Agarwal MK, et al. p53-dependent p21-mediated growth arrest pre-empts and protects HCT116 cells from PUMA-mediated apoptosis induced by EGCG. Cancer Lett. 2010;296:225-32.
59. Trudel D, Labbe DP, Araya-Farias M, et al. A two stage singe arm, phase II study of EGCG-enriched green tea drink as amaintenance therapy in women with advanced stage ovarian cancer. Gynecol Oncol. 2013;13(2):357-61.
60. .• Grivennikov SI, Wang K, Mucida D, et al. Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth. Nature. 2012;491(7423):254-8. The authors present a very detailed molecular analysis of the role of microbial colonic flora in the development of adenomas. The results indicate the importance of IL-17 and IL-23 signaling and mucosal barrier integrity in colon adenoma and cancer growth..
61. Kostic AD, Gevers D, Pedamallu CS, et al. Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res. 2012;22(2):292-8.
62. Arthur JC, Perez-Chanona E, Muhlbauer M, et al. Intestinal inflammation targets cancer-inducing activity of the microbiota. Science. 2012;338(6103):120-3.
63. Chong ES. A potential role of probiotics in colorectal cancer prevention: review of possible mechanisms of action. World J Microbiol Biotechnol. 2013. doi:10.1007/s11274-013-1499-6.
64. Chen X, Kokkotou EG, Mustafa N, Bhaskar KR, Sougioultzis S, O'Brien M, et al. Saccharomyces boulardii inhibits ERK1/2 mitogen-activated protein kinase activation both in vitro and in vivo and protects against Clostridium difficile toxin A-induced enteritis. J Biol Chem. 2006;281:24449-54. (Pubitemid 44274218)
65. Matsumoto M, Kurihara S, Kibe R, Ashida H, Benno Y. Longevity in mice is promoted by probiotic-induced suppression of colonic senescence dependent on up regulation of gut bacterial polyamine production. PLoS ONE. 2011;6:e23652.
66. Park E, Jeon GI, Park JS, Paik HD. A probiotic strain of Bacillus polyfermenticus reduces DMH induced precancerous lesions in F344 male rat. Biol Pharm Bull. 2007;30:569-74. (Pubitemid 46355951)
67. Cho E, Smith-Warner SA, Ritz J, et al. Alcohol intake and colorectal cancer: a pooled analysis of 8 cohort studies. Ann Intern Med. 2004;140:603-13.
68. .• Haas SL, Ye W, Lohr JM. Alcohol consumption and digestive tract cancer. Curr Opin Clin Nutr Metab Care. 2012;15:457-67. This review summarizes recent evidence on the impact of alcohol consumption on the risk of gastrointestinal neoplasms. It presents current knowledge of the molecular bases of ethanol-induced carcinogenesis, mostly through oxidative stress mechanisms and DNA damage caused by the ethanol metabolite acetaldehyde. The authors also present the results of recent systematic reviews which indicate that alcohol intake is strongly related to increased risk of gastrointestinal cancers (including colon cancer).
69. Blasiak J, Trzeciak A, Malecka-Panas E, Drzewoski J, Wojewodzka M. In vitro genotoxicity of ethanol and acetaldehyde in human lymphocytes and the gastrointestinal tract mucosa cells. Toxicol In Vitro. 2000;14:287-95. (Pubitemid 30440596)
70. Jacobson JS, Neugut AI, Murray T, Garbowski GC, Forde KA, Treat MR, et al. Cigarette smoking and other behavioral risk factors for recurrence of colorectal adenomatous polyps (New York City, NY, USA). Cancer Causes Control. 1994;5:215-20. (Pubitemid 24186009)
71. Leufkens AM, Van Duijnhoven FJ, Siersema PD, et al. Cigarette smoking and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition study. Clin Gastroenterol Hepatol. 2011;9(2):137-44.
72. 7-nicotinicacetylcholine receptor and cross-talk between 5-lipoxygenase and cyclooxygenase-2 in colon cancer growth induced by4-(N-meth-yl- N-nitrosamino)-1-(3-pyridyl)-1-butanone. J Pharmacol Exp Ther. 2004;311:123-30.
73. Wong HP, Yu L, Lam EK, Tai EK, Wu WK, Cho CH. Nicotine promotes colon tumor growth and angiogenesis through β-adrenergic activation. Toxicol Sci. 2007;97:279-87. (Pubitemid 47073845)
74. Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M. Bodymass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet. 2008;371:569-78. (Pubitemid 351232031)
75. 2 were associated with 14%, 19%, 24% and 41% increased risks of colorectal cancer, respectively." Additionally "the association was stronger for colon than rectal cancer, for men than women," These valuable data strongly emphasize the impact of obesity on CRC risk..
76. Moghaddam AA, Woodward M, Huxley R. Obesity and risk of colorectal cancer: a meta-analysis of 31 studies with 70,000 events. Cancer Epidemiol Biomarkers Prev. 2007;16:2533-47. (Pubitemid 351196307)
77. 3) had a positive association with larger adenomas (>or=10 mm) and multiple adenomas." The results presented indicate that abdominal visceral adipose tissue volume is a better predictor of colorectal adenomas than BMI or waist circumference in men and women..
78. Gutierez DA, Puglisi MJ, Hasty AH. Impact of increased adipose tissue mass on inflammation, insulin resistance, and dyslipidemia. Curr Diabetes Rep. 2009;9(1):26-32.
79. Chavez JA, Summers SA. Lipid oversupply, selective insulin resistance, and lipotoxicity: molecular mechanisms. Biochim Biophys Acta. 1801;2010:252-65.
80. Calle EE, Kaaks R. Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer. 2004;4:579-91. (Pubitemid 39025053)
81. Kumor A, Daniel P, Pietruczuk M, Malecka-Panas E. Serum leptin, adiponectin, and resistin concentration in colorectal adenoma and carcinoma (CC) patients. Int J Colorectal Dis. 2009;24:275-81.
82. Booth FW, Chakravarthy MV, Gordon SE, Spangenburg EE. Waging war on physical inactivity: using modern molecular ammunition against an ancient enemy. J Appl Physiol. 2002;93:3-30. (Pubitemid 34686188)
83. Wolin KY, Yan Y, Colditz GA, et al. Physical activity and colon cancer prevention: a meta-analysis. Br J Cancer. 2009; 100:611-6.
84. •• Wolin KY, Yan Y, Colditz GA. Physical activity and risk of colon adenoma: a meta-analysis. Br J Cancer. 2011;104(5):882-5. This is ameta-analysis of 20 studies evaluating the association between physical activity and the prevalence of colon adenomas. The authors showed that "a significant inverse association between physical activity and colon adenomas was found with an overall RR of 0.84 (CI: 0.77-0.92). The association was similar in men (RR=0.81, CI: 0.67-0.98) and women (RR=0.87, CI: 0.74-1.02). The association appeared slightly stronger in large/advanced polyps (RR=0.70, CI: 0.56-0.88)." The study strongly emphasizes the important role of physical activity in CRC prevention..
85. Handschin C, Spiegelman BM. The role of exercise and PGC1α in inflammation and chronic disease. Nature. 2008;454:463-9.
86. Wiseman M. The second World Cancer Research Fund/American Institute for Cancer Research expert report. Food, nutrition, physical activity, and the prevention of cancer: a global perspective. Proc Nutr Soc. 2008;67:253-6.
87. Asghar M, George L, Lokhandwala MF. Exercise decreases oxidative stress and inflammation restores renal dopamine D1 receptor function in old rats. Am J Physiol Renal Physiol. 2007;293:F914-9. (Pubitemid 47403363)
88. Cirillo D, Rachiglio AM, la Montagna R, Giordano A, Normanno N. Leptin signaling in breast cancer: an overview. J Cell Biochem. 2008;105:956-64.
89. Drevon CA. Fatty acids and expression of adipokines. Biochim Biophys Acta. 2005;1740:287-92.
90. Kim SY, Jun TW, Lee YS, Na HK, Surh YJ, Song W. Effects of exercise on cyclooxygenase-2 expression and nuclear factor-κB DNA binding in human peripheral blood mononuclear cells. Ann N YAcad Sci. 2009;1171:464-71.
91. Poulsen HE, Weimann A, Loft S. Methods to detect DNA damage by free radicals: relation to exercise. Proc Nutr Soc. 1999;58:1007-14. (Pubitemid 30238890)
92. Min/+ mice and azoxymethane/dextransulfate sodium-treated mice. BMC Cancer. 2008;8:316. doi:10.1186/1471-2407-8-316.
93. Hrushesky WJ, Lannin D, Haus E. Evidence for an ontogenetic basis for circadian coordination of cancer cell proliferation. J Natl Cancer Inst. 1998;90:1480-4. (Pubitemid 28482013)
94. Matsuo T, Yamaguchi S, Mitsui S, Emi A, Shimoda F, Okamura H. Control mechanism of the circadian clock for timing of cell division in vivo. Science. 2003;302:255-9. (Pubitemid 37248750)
95. Ko CH, Takahashi JS. Molecular components of the mammalian circadian clock. Hum Mol Genet. 2006;15:R271-7. (Pubitemid 44446803)
96. Min/+ tumorigenesis. Mol Cancer Res. 2008;6:1786-93.
97. Wozniak K, Arabski M, Malecka-Panas E, Drzewoski J, Blasiak J. DNA damage in human colonic mucosa cells induced by bleomycin and the protective action of vitamin E. Cell Mol Biol Lett. 2003;9:31-45.
98. Blasiak J, Arabski M, Pertynski T, Malecka-Panas E, et al. DNA damage in human colonic mucosa cells evoked by nickel and protective action of quecetin - involvement of free radicals? Cell Biol Toxicol. 2002;18:279-88. (Pubitemid 34831223)
99. Flossmann E, Rothwell PM. Effect of aspirin on long-term risk of colorectal cancer: consistent evidence from randomized and observational studies. Lancet. 2007;369:1603-13. (Pubitemid 46710123)
100. Liao X, Lochhead P, Nishihara R. Aspirin use, tumor PIK3CA mutation, and colorectal-cancer survival. N Engl J Med. 2012;367(17):1596-606.