Ernährungsfaktoren, Gen-Nährstoff-Interaktion und kolorektales Karzinom - eine Übersicht des aktuellen Kenntnisstandes

Zusammenfassung

Die Entstehung kolorektaler Karzinome wird maßgeblich durch die Ernährungsweise beeinflusst. Aktuelle Kohortenstudien und Metaanalysen erlauben eine Neubewertung der Risikomodifikation im Hinblick auf einzelne Lebensmittelgruppen sowie auf bestimmte Nährstoffe wie Ballaststoffe und Folsäure. Auf Basis der Evidenzkriterien der WHO/FAO zeigt sich, dass ein risikosenkender Effekt eines hohen Obstverzehrs als möglich, der eines hohen Gemüseverzehrs als wahrscheinlich einzustufen ist. Insbesondere in roher Form kommt Obst und Gemüse vermutlich ein antikanzerogenes Potenzial zu. Die Evidenz für einen risikosenkenden Effekt des Vollkornverzehrs im Hinblick auf Tumoren des Kolons und Rektums gilt als möglich, wohingegen die Evidenz für eine potenzielle Risikoerhöhung durch einen hohen Verzehr an Auszugsmehlprodukten und Süßwaren trotz einiger Hinweise (noch) als unzureichend zu bewerten ist. Bei Milch(produkten) wird die Evidenz für einen risikosenkenden Effekt als möglich bewertet. Demgegenüber spricht die Datenlage bei Eiern und rotem Fleisch für einen möglichen risikoerhöhenden Effekt. Deutlichere Hinweise auf einen risikosteigernden Effekt ergeben sich für Fleischwaren, so dass die Evidenz in Bezug auf das kolorektale Karzinom hier als wahrscheinlich eingestuft wird. Aufgrund widersprüchlicher Interpretationen der Datenlage wird die Evidenz für einen risikosenkenden Effekt von Ballaststoffen bei Dickdarmkrebs als möglich oder unzureichend eingestuft. Im Gegensatz zu früheren Bewertungen scheinen fettreiche Ernährungsformen nur indirekt das Krebsrisiko zu steigern, indem sie im Rahmen einer hyperkalorischen Kost zur Entwicklung von Übergewicht beitragen. So gilt die Evidenz, dass Übergewicht, insbesondere viszerale Adipositas, das Risiko für Dickdarmkarzinome erhöht, heute als überzeugend.

Beobachtungsstudien untermauern die Vermutung, dass eine unzureichende Folsäure-Versorgung die Entstehung kolorektaler Tumore begünstigt. Für einen derartigen Zusammenhang sprechen insbesondere die Ergebnisse prospektiver Studien, wenngleich die Datenlage z.T. uneinheitlich ist. Eine Ursache für die widersprüchlichen Studienergebnisse könnte in der genetischen Variabilität, insbesondere im Gen-Polymorphismus des Enzyms Methylentetrahydrofolat-Reduktase (MTHFR), zu suchen sein. Insbesondere Träger des MTHFR-677-TT-Genotyps sind bei schlechter Folatversorgung einem erhöhten Krankheitsrisiko ausgesetzt.

Im Rahmen der Primärprävention ist eine vorwiegend pflanzlich orientierte Kost, die einen hohen Anteil an Gemüse, Obst, Vollkornprodukten und Hülsenfrüchten aufweist zu empfehlen, ergänzt um Nüsse, fettarme Milchprodukte, Fischgerichte und Geflügel. Dagegen sollte der Konsum von energiereichen Süßwaren, Auszugsmehlprodukten und Fleischwaren eingeschränkt werden.

Summary

Diet plays an important role in the pathogenesis of colorectal cancer. Current cohort studies and meta analysis enable a reevaluation of how food or nutrients such as fiber and folic acid influence cancer risk. Based on the evidence criteria of the WHO/FAO, risk reduction by a high intake of fruit is assessed as possible, while a lowered risk by a high vegetable intake is probable. Especially raw vegetables and fruits seem to exert anticancer properties. The evidence of a risk reducing effect of whole grain relating to colorectal cancer is assessed as probable whereas the evidence of an increased risk by high consumption of refined white flour products and sweets is (still) insufficient despite some evidences. There is a probable risk reducing effect of milk and dairy products. The available data on eggs and red meat indicate a possible risk increasing influence. Stronger clues for a risk increasing effect have been shown for meat products leading to evidence assessed as probable. Owing to varied interpretations of the data on fiber, the evidence of a risk reducing effect relating to colorectal cancer is assessed as possible or insufficient. In contrast to former evaluations, diets rich in fat seem to increase colorectal cancer risk only indirectly as part of a hypercaloric diet by advancing the obesity risk. Thus, the evidence of obesity, especially visceral obesity, as a risk of colorectal cancer is judged as convincing today.

Epidemiological studies suggest that insufficient folic acid intake may elevate the risk of colorectal cancer. Although the data is partly controversial, especially results of prospective studies support this association. One reason for the contradictory results may be the genetic variability especially the MTHFR polymorphism. Individuals with the homozygote genotype for the MTHFR (677C → T) polymorphism are at higher risk when folic acid supply is low. As primary prevention, a diet rich in vegetables, fruits, whole grain products, and legumes added by nuts, low-fat dairy products, fish, and poultry can be recommended. In contrast the consumption of sweets, refined white flour products and meat products should be reduced.

“What are we to do when the irresistible force of the need to offer clinical advice meets with the immovable object of flawed evidence? All we can do is our best: give the advice, but alert the advisees to the flaws in the evidence on which it is based.” [22]

Schlüsselwörter

Ernährung - kolorektales Karzinom - Folsäure - MTHFR-Polymorphismus

Keywords

diet - nutrition - colorectal cancer - folic acid - MTHFR polymorphism

Literatur

• 001 Albanes D, Malila N, Taylor P R, Huttunen J K, Virtamo J, Edwards B K, Rautalahti M, Hartman A M, Barrett M J, Pietinen P, Hartman T J, Sipponen P, Lewin K, Teerenhovi L, Hietanen P, Tangrea J A, Virtanen M, Heinonen O P. Effects of supplemental alpha-tocopherol and beta-carotene on colorectal cancer: results from a controlled trial (Finland).  Cancer Causes Control. 2000;  11 197-205
• 002 Arts I C, Hollman P C. Polyphenols and disease risk in epidemiologic studies.  Am J Clin Nutr. 2005;  81 317S-325S
• 003 Augustin L S, Franceschi S, Jenkins D J, Kendall C W, Vecchia C La. Glycemic index in chronic disease: a review.  Eur J Clin Nutr. 2002;  56 1049-71
• 004 Baron J A. Dietary fiber and colorectal cancer: an ongoing saga.  JAMA. 2005;  294 2904-6
• 005 Biasco G, Zannoni U, Paganelli G M, Santucci R, Gionchetti P, Rivolta G, Miniero R, Pironi L, Calabrese C, Febo G Di, Miglioli M. Folic acid supplementation and cell kinetics of rectal mucosa in patients with ulcerative colitis.  Cancer Epidemiol Biomarkers Prev. 1997;  6 469-71
• 006 Bingham S A, Day N E, Luben R, Ferrari P, Slimani N, Norat T, Clavel-Chapelon F, Kesse E, Nieters A, Boeing H, Tjonneland A, Overvad K, Martinez C, Dorronsoro M, Gonzalez C A, Key T J, Trichopoulou A, Naska A, Vineis P, Tumino R, Krogh V, Bueno-de-Mesquita H B, Peeters P H, Berglund G, Hallmans G, Lund E, Skeie G, Kaaks R, Riboli E. European Prospective Investigation into Cancer and Nutrition: 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
• 007 Bingham S A. Diet and colorectal cancer prevention.  Biochem Soc Trans. 2000;  28 12-6
• 008 Boeing H. Tumorentstehung - hemmende und fördernde Ernährungsfaktoren. In: Deutsche Gesellschaft für Ernährung (Hrsg.): Ernährungsbericht 2004. Bonn; 2004: 235-282
• 009 Boutron-Ruault M C, Senesse P, Faivre J, Couillault C, Belghiti C. Folate and alcohol intakes: related or independent roles in the adenoma-carcinoma sequence?.  Nutr Cancer. 1996;  26 337-46
• 010 Calvert P M, Frucht H. The genetics of colorectal cancer.  Ann Intern Med. 2002;  137 603-12
• 011 Chatenoud L, Tavani A, Vecchia C La, Jacobs Jr D R, Negri E, Levi F. et al. . Whole grain food intake and cancer risk.  Int J Cancer. 1998;  77 24-8
• 012 Chen J, Giovannucci E, Kelsey K, Rimm E B, Stampfer M J, Colditz G A, Spiegelman D, Willett W C, Hunter D J. A methylenetetrahydrofolate reductase polymorphism and the risk of colorectal cancer.  Cancer Res. 1996;  56 4862-4
• 013 Cho E, Smith-Warner S A, Spiegelman D, Beeson W L, Brandt P A van den, Colditz G A. et al. . Dairy foods, calcium, and colorectal cancer: a pooled analysis of 10 cohort studies.  J Natl Cancer Inst. 2004;  96 1015-22
• 014 Ciccarone E, Castelnuovo A Di, Salcuni M, Siani A, Giacco A, Donati  M B, Gaetano G De, Capani F, Iacoviello L. Gendiabe Investigators: A high-score Mediterranean dietary pattern is associated with a reduced risk of peripheral arterial disease in Italian patients with Type 2 diabetes.  J Thromb Haemost. 2003;  1 1744-52
• 015 Combs Jr G F, Clark L C, Turnbull B W. An analysis of cancer prevention by selenium.  Biofactors. 2001;  14 153-9
• 016 Cravo M, Fidalgo P, Pereira A D, Gouveia-Oliveira A, Chaves P, Selhub J, Mason J B, Mira F C, Leitao C N. DNA methylation as an intermediate biomarker in colorectal cancer: modulation by folic acid supplementation.  Eur J Cancer Prev. 1994;  3 473-9
• 017 Cravo M L, Pinto A G, Chaves P, Cruz J A, Lage P, Nobre Leitao C, Costa F. Effect of folate supplementation on DNA methylation of rectal mucosa in patients with colonic adenomas: correlation with nutrient intake.  Clin Nutr. 1998;  17 45-9
• 018 Delgado-Enciso I, Martinez-Garza S G, Rojas-Martinez A, Ortiz-Lopez R, Bosques-Padilla F, Calderon-Garciduenas A L, Zarate-Gomez M, Barrera-Saldana H A. 677T mutation of the MTHFR gene in adenomas and colorectal cancer in a population sample from the Northeastern Mexico. Preliminary results.  Rev Gastroenterol Mex. 2001;  66 32-7
• 019 Doll R, Peto R. The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today.  J Natl Cancer Inst. 1981;  66 1191-308
• 020 Duffield-Lillico A J, Reid M E, Turnbull B W, Combs Jr G F, Slate E H, Fischbach L A, Marshall J R, Clark L C. Baseline characteristics and the effect of selenium supplementation on cancer incidence in a randomized clinical trial: a summary report of the Nutritional Prevention of Cancer Trial.  Cancer Epidemiol Biomarkers Prev. 2002;  11 630-9
• 021 Ferraroni M, Vecchia C CLa, D'Avanzo B, Negri E, Franceschi S, Decarli A. Selected micronutrient intake and the risk of colorectal cancer.  Br J Cancer. 1994;  70 1150-55
• 022 Fletcher S, Sackett D L. Canadian Task Force on the periodic health examination: The periodic health examination.  CMAJ. 1979;  121 1193-1254
• 023 Flood A, Caprario L, Chaterjee N, Lacey Jr J V, Schairer C, Schatzkin A. Folate, methionine, alcohol, and colorectal cancer in a prospective study of women in the United States.  Cancer Causes Control. 2002;  13 551-61
• 024 Flood A, Peters U, Chatterjee N, Lacey Jr J V, Schairer C, Schatzkin A. Calcium from diet and supplements is associated with reduced risk of colorectal cancer in a prospective cohort of women.  Cancer Epidemiol Biomarkers Prev. 2005;  14 126-32
• 025 Flood A, Velie E M, Chaterjee N, Subar A F, Thompson F E, Lacey Jr J V, Schairer C, Troisi R, Schatzkin A. Fruit and vegetable intakes and the risk of colorectal cancer in the Breast Cancer Detection Demonstration Project follow-up cohort.  Am J Clin Nutr. 2002;  75 936-43
• 026 Flood A, Velie E M, Sinha R, Chaterjee N, Lacey Jr J V, Schairer C, Schatzkin A. Meat, fat, and their subtypes as risk factors for colorectal cancer in a prospective cohort of women.  Am J Epidemiol. 2003;  158 59-68
• 027 Franceschi S, Maso L Dal, Augustin L, Negri E, Parpinel M, Boyle P, Jenkins D J, Vecchia C La. Dietary glycemic load and colorectal cancer risk.  Ann Oncol. 2001;  12 173-8
• 028 Freudenheim J L, Graham S, Marshall J R, Haughey B P, Cholewinski S, Wilkinson G. Folate intake and carcinogenesis of the colon and rectum.  Int J Epidemiol. 1991;  20 368-74
• 029 Fuchs C S, Willett W C, Colditz G A, Hunter D J, Stampfer M J, Speizer F E, Giovannucci E L. The influence of folate and multivitamin use on the familial risk of colon cancer in women.  Cancer Epidemiol Biomarkers Prev. 2002;  11 227-34
• 030 Fung T T, Schulze M, Manson J E, Willett W C, Hu F B. Dietary patterns, meat intake, and the risk of type 2 diabetes in women.  Arch Intern Med. 2004;  164 2235-40
• 031 Fung T T, Stampfer M J, Manson J E, Rexrode K M, Willett W C, Hu F B. Prospective study of major dietary patterns and stroke risk in women.  Stroke. 2004;  35 2014-9
• 032 Fung T T, Willett W C, Stampfer M J, Manson J E, Hu F B. Dietary patterns and the risk of coronary heart disease in women.  Arch Intern Med. 2001;  161 1857-62
• 033 Gatof D, Ahnen D. Primary prevention of colorectal cancer: diet and drugs.  Gastroenterol Clin North Am. 2002;  31 587-623
• 034 Giovannucci E, Rimm e B, Ascherio A, Stampfer M J, Colditz G A, Willett W C. Alcohol, low-methionine-low-folate diets, and risk of colon cancer in men.  J Natl Cancer Inst. 1995;  87 265-73
• 035 Giovannucci E, Stampfer M J, Colditz G A, Hunter D J, Fuchs C, Rosner B A, Speizer F E, Willett W C. Multivitamin use, folate, and colon cancer in women in the Nurses' Health Study.  Ann Intern Med. 1998;  129 517-24
• 036 Giovannucci E. The epidemiology of vitamin D and colorectal cancer: recent findings.  Curr Opin Gastroenterol. 2006;  22 24-9
• 037 Glynn S A, Albanes d, Pietinen P, Brown C C, Rautalahti M, Tangrea J A, Gunter E W, Barrett M J, Virtamo J, Taylor P R. Colorectal cancer and folate status: a nested case-control study among male smokers.  Cancer Epidemiol Biomarkers Prev. 1996;  5 487-94
• 038 Gröber U. Orthomolekulare Medizin. Stuttgart; Wissenschaftliche Verlagsgesellschaft 2000
• 039 Harnack L, Jacobs Jr D R, Nicodemus K, Lazovich D, Anderson K, Folsom A R. Relationship of folate, vitamin B-6, vitamin B-12, and methionine intake to incidence of colorectal cancers.  Nutr Cancer. 2002;  43 152-8
• 040 Higginbotham S, Zhang Z F, Lee I M, Cook N R, Giovannucci E, Buring J E, Liu S. Women's Health Study: Dietary glycemic load and risk of colorectal cancer in the Women's Health Study.  J Natl Cancer Inst. 2004;  96 229-33
• 041 HOPE and HOPE-TOO Trial Investigators . Effects of long-term vitamin E supplementation on cardiovascular events and cancer.  JAMA. 2005;  293 1338-1347
• 042 Howe G R, Aronson K J, Benito E, Castelleto R, Cornee J, Duffy S, Gallagher R P, Iscovich J M, Deng-ao J, Kaaks R, Kune G A, Kune S, Lee H P, Lee M, Miller A B, Peters R K, Potter J D, Riboli E, Slattery M L, Trichopoulos D, Tuyns A, Tzonou A, Watson L F, Whittemore A S, Shu Z. The relationship between dietary fat intake and risk of colorectal cancer: evidence from the combined analysis of 13 case-control studies.  Cancer Causes Control. 1997;  8 215-28
• 043 Hu F B, Rimm E B, Stampfer M J, Ascherio A, Spiegelman D, Willett W C. Prospective study of major dietary patterns and risk of coronary heart disease in men.  Am J Clin Nutr. 2000;  72 912-21
• 044 Hülsmann O, Ströhle A, Wolters M, Hahn A. Selen und Zink in Prävention und Therapie.  Dtsch Apothek Z. 2005;  145 1288-1296
• 045 IARC Working Group on the Evaluation of cancer-Prevention Strategies .IARC handbooks of cancer prevention: weight control and physical activity. Lyon; IARC 2003a
• 046 IARC Working Group on the Evaluation of cancer-Prevention Strategies .IARC handbooks of cancer prevention: fruit and vegetables. Lyon; IARC 2003b
• 047 Jacobs Jr D R, Marquart L, Slavin J, Kushi L H. Whole-grain intake and cancer: an expanded review and meta-analysis.  Nutr Cancer. 1998;  30 85-96
• 048 Jacobs E J, Connell C J, Chao A, McCullough M L, Rodriguez C, Thun M J, Calle E E. Multivitamin use and colorectal cancer incidence in a US cohort: does timing matter?.  Am J Epidemiol. 2003;  158 621-8
• 049 Jacobs E J, Connell C J, Patel A V, Chao A, Rodriguez C, Seymour J, McCullough M L, Calle E E, Thun M J. Multivitamin use and colon cancer mortality in the Cancer Prevention Study II cohort (United States).  Cancer Causes Control. 2001;  12 927-34
• 050 Jarvinen R, Knekt P, Hakulinen T, Rissanen H, Heliovaara M. Dietary fat, cholesterol and colorectal cancer in a prospective study.  Br J Cancer. 2001;  85 357-61
• 051 Kato I, Dnistrian A M, Schwartz M, Toniolo P, Koenig K, Shore R E, Akhmedkhanov A, Zeleniuch-Jacquotte A, Riboli E. Serum folate, homocysteine and colorectal cancer risk in women: a nested case-control study.  Br J Cancer. 1999;  79 1917-22
• 052 Keku T, Millikan R, Worley K, Winkel S, Eaton A, Biscocho L, Martin C, Sandler R. 5,10-Methylenetetrahydrofolate reductase codon 677 and 1298 polymorphisms and colon cancer in African Americans and whites.  Cancer Epidemiol Biomarkers Prev. 2002;  11 1611-21
• 053 Kesse E, Boutron-Ruault M C, Norat T, Riboli E, Clavel-Chapelon F. E3N Group: Dietary calcium, phosphorus, vitamin D, dairy products and the risk of colorectal adenoma and cancer among French women of the E3N-EPIC prospective study.  Int J Cancer. 2005;  117 137-44
• 054 Key T J, Schatzkin A, Willett W C, Allen N E, Spencer E A, Travis R C. Diet, nutrition and the prevention of cancer.  Public Health Nutr. 2004;  7 187-200
• 055 Khosraviani K, Weir H P, Hamilton P, Moorehead J, Williamson K. Effect of folate supplementation on mucosal cell proliferation in high risk patients for colon cancer.  Gut. 2002;  51 195-9
• 056 Kim Y I, Baik H W, Fawaz K, Knox T, Lee Y M, Norton R, Libby E, Mason J B. Effects of folate supplementation on two provisional molecular markers of colon cancer: a prospective, randomized trial.  Am J Gastroenterol. 2001;  96 184-95
• 057 Vecchia C La, Negri E, Pelucchi C, Franceschi S. Dietary folate and colorectal cancer.  Int J Cancer. 2002;  102 545-7
• 058 Larsson S C, Giovannucci E, Bergkvist L, Wolk A. Whole grain consumption and risk of colorectal cancer: a population-based cohort of 60 000 women.  Br J Cancer. 2005;  92 1803-7
• 059 Lashner B A, Heidenreich P A, Su G L, Kane S V, Hanauer S B. Effect of folate supplementation on the incidence of dysplasia and cancer in chronic ulcerative colitis. A case-control study.  Gastroenterology. 1989;  97 255-59
• 060 Lashner B A, Provencher K S, Seidner D L, Knesebeck A, Brzezinski A. The effect of folic acid supplementation on the risk for cancer or dysplasia in ulcerative colitis.  Gastroenterology. 1997;  112 29-32
• 061 Lashner B A. Red blood cell folate is associated with the development of dysplasia and cancer in ulcerative colitis.  J Cancer Res Clin Oncol. 1993;  119 549-54
• 062 Marchand L Le, Donlon T, Hankin J H, Kolonel L N, Wilkens L R, Seifried A. B-vitamin intake, metabolic genes, and colorectal cancer risk (United States).  Cancer Causes Control. 2002;  13 239-48
• 063 Lin J, Zhang S M, Cook N R, Lee I M, Buring J E. Dietary fat and fatty acids and risk of colorectal cancer in women.  Am J Epidemiol. 2004;  160 1011-22
• 064 Lin J, Zhang S M, Cook N R, Manson J E, Lee I M, Buring J E. Intakes of calcium and vitamin D and risk of colorectal cancer in women.  Am J Epidemiol. 2005;  161 755-64
• 065 Lin J, Zhang S M, Cook N R, Rexrode K M, Lee I M, Buring J E. Body mass index and risk of colorectal cancer in women (United States).  Cancer Causes Control. 2004;  15 581-9
• 066 Lin J, Zhang S M, Cook N R, Rexrode K M, Liu S, Manson J E. et al. . Dietary intakes of fruit, vegetables, and fiber, and risk of colorectal cancer in a prospective cohort of women (United States).  Cancer Causes Control. 2005;  16 225-33
• 067 Link L B, Potter J D. Raw versus cooked vegetables and cancer risk.  Cancer Epidemiol Biomarkers Prev. 2004;  13 1422-35
• 068 Ma J, Stampfer M J, Giovannucci E, Artigas C, Hunter D J, Fuchs C, Willett W C, Selhub J, Hennekens C H, Rozen R. Methylenetetrahydrofolate reductase polymorphism, dietary interactions, and risk of colorectal cancer.  Cancer Res. 1997;  57 1098-102
• 069 MacLean C H, Newberry S J, Mojica W A, Khanna P, Issa A M, Suttorp M J, Lim Y W, Traina S B, Hilton L, Garland R, Morton S C. Effects of omega-3 fatty acids on cancer risk: a systematic review.  JAMA. 2006;  295 403-15
• 070 McCullough M L, Giovannucci E L. Diet and cancer prevention.  Oncogene. 2004;  23 6349-64
• 071 Meyer F, White E. Alcohol and nutrients in relation to colon cancer in middle-aged adults.  Am J Epidemiol. 1993;  138 225-36
• 072 Michaud D S, Fuchs C S, Liu S, Willett W C, Colditz G A, Giovannucci E. Dietary glycemic load, carbohydrate, sugar, and colorectal cancer risk in men and women.  Cancer Epidemiol Biomarkers Prev. 2005;  14 138-47
• 073 Michels K B, Giovannucci E, Joshipura K J, Rosner B A, Stampfer M J, Fuchs C S, Colditz G A, Speizer F E, Willett W C. Prospective study of fruit and vegetable consumption and incidence of colon and rectal cancers.  J Natl Cancer Inst. 2000;  92 1740-52
• 074 Michels K B, Wolk A. A prospective study of variety of healthy foods and mortality in women.  Int J Epidemiol. 2002;  31 847-54
• 075 Michels K B. The role of nutrition in cancer development and prevention.  Int J Cancer. 2005;  114 163-5
• 076 Montonen J, Knekt P, Harkanen T, Jarvinen R, Heliovaara M, Aromaa A, Reunanen A. Dietary patterns and the incidence of type 2 diabetes.  Am J Epidemiol. 2005;  161 219-27
• 077 Nkondjock A, Shatenstein B, Maisonneuve P, Ghadirian P. Specific fatty acids and human colorectal cancer: an overview.  Cancer Detect Prev. 2003;  27 55-66
• 078 Norat T, Bingham S, Ferrari P, Slimani N, Jenab M. et al. . Meat, fish, and colorectal cancer risk: the European Prospective Investigation into cancer and nutrition.  J Natl Cancer Inst. 2005;  97 906-16
• 079 Norat T, Lukanova A, Ferrari P, Riboli E. Meat consumption and colorectal cancer risk: dose-response meta-analysis of epidemiological studies.  Int J Cancer. 2002;  98 241-56
• 080 Oh K, Willett W C, Fuchs C S, Giovannucci E L. Glycemic index, glycemic load, and carbohydrate intake in relation to risk of distal colorectal adenoma in women.  Cancer Epidemiol Biomarkers Prev. 2004;  13 1192-8
• 081 Osler M, Heitmann B L, Hoidrup S, Jorgensen L M, Schroll M. Food intake patterns, self rated health and mortality in Danish men and women. A prospective observational study.  J Epidemiol Community Health. 2001;  55 399-403
• 082 Park K S, Mok J W, Kim J C. The 677C > T mutation in 5,10-methylenetetrahydrofolate reductase and colorectal cancer risk.  Genet Test. 1999;  3 233-6
• 083 Park Y, Hunter D J, Spiegelman D, Bergkvist L, Berrino F, Brandt P A van den, Buring J E. et al. . Dietary fiber intake and risk of colorectal cancer: a pooled analysis of prospective cohort studies.  JAMA. 2005;  294 2849-57
• 084 Parkin D M, Bray F, Ferlay J, Pisani P. Estimating the world cancer burden: Globocan 2000.  Int J Cancer. 2001;  94 153-6
• 085 Pufulete M, Al-Ghnaniem R, Leather A J, Appleby P, Gout S, Terry C, Emery P W, Sanders T A. Folate status, genomic DNA hypomethylation, and risk of colorectal adenoma and cancer: a case control study.  Gastroenterology. 2003;  124 1240-8
• 086 Riboli E, Norat T. Epidemiologic evidence of the protective effect of fruit and vegetables on cancer risk.  Am J Clin Nutr. 2003;  78 559S-569S
• 087 Sachse C, Smith G, Wilkie M J, Barrett J H, Waxman R, Sullivan F, Forman D, Bishop D T, Wolf C R. Colorectal Cancer Study Group. A pharmacogenetic study to investigate the role of dietary carcinogens in the etiology of colorectal cancer.  Carcinogenesis. 2002;  23 1839-49
• 088 Sandhu M S, White I R, McPherson K. Systematic review of the prospective cohort studies on meat consumption and colorectal cancer risk: a meta-analytical approach.  Cancer Epidemiol Biomarkers Prev. 2001;  10 439-46
• 089 Sato Y, Tsubono Y, Nakaya N, Ogawa K, Kurashima K, Kuriyama S, Hozawa A, Nishino Y, Shibuya D, Tsuji I. Fruit and vegetable consumption and risk of colorectal cancer in Japan: The Miyagi Cohort Study.  Public Health Nutr. 2005;  8 309-14
• 090 Shannon B, Gnanasampanthan S, Beilby J, Iacopetta B. A polymorphism in the methylenetetrahydrofolate reductase gene predisposes to colorectal cancers with microsatellite instability.  Gut. 2002;  50 520-4
• 091 Sharp L, Little J, Brockton N. et al. . Genetic polymorphisms in folate metabolism, dietary folate intake and colorectal cancer: a population-based case-control study.  J Epidemiol Community Health. 2001;  55 A27
• 092 Sharp L, Little J, Brockton N, Cotton S C, Haites N E, Cassidy J. Dietary Intake of Folate and Related Micronutrients, Genetic Polymorphisms in MTHFR and Colorectal Cancer: A Population-Based Case-Control Study in Scotland.  J Nutr. 2002;  132 3542S
• 093 Sharp L, Little J. Polymorphisms in genes involved in folate metabolism and colorectal neoplasia: a HuGE review.  Am J Epidemiol. 2004;  159 423-43
• 094 Slattery M L, Curtin K P, Edwards S L, Schaffer D M. Plant foods, fiber, and rectal cancer.  Am J Clin Nutr. 2004;  79 274-81
• 095 Slattery M L, Neuhausen S L, Hoffman M, Caan B, Curtin K, Ma K N, Samowitz W. Dietary calcium, vitamin D, VDR genotypes and colorectal cancer.  Int J Cancer. 2004;  111 750-6
• 096 Slattery M L, Potter J D, Samowitz W, Schaffer D, Leppert M. Methylenetetrahydrofolate reductase, diet, and risk of colon cancer.  Cancer Epidemiol Biomarkers Prev. 1999;  8 513-8
• 097 Slattery M L, Schaffer D, Edwards S L, Ma K N, Potter J D. Are dietary factors involved in DNA methylation associated with colon cancer?.  Nutr Cancer. 1997;  28 52-62
• 098 Stein C J, Colditz G A. Modifiable risk factors for cancer.  Br J Cancer. 2004;  90 299-303
• 099 Steinmetz K A, Potter J D. Egg consumption and cancer of the colon and rectum.  Eur J Cancer Prev. 1994;  3 237-45
• 100 Ströhle A, Wolters M, Hahn A. Folic acid and colorectal cancer prevention: molecular mechanisms and epidemiological evidence (Review).  Int J Oncol. 2005;  26 1449-64
• 101 Su L J, Arab L. Nutritional status of folate and colon cancer risk: evidence from NHANES I epidemiologic follow-up study.  Ann Epidemiol. 2001;  11 65-72
• 102 Terry P, Jain M, Miller A B, Howe G R, Rohan T E. Dietary intake of folic acid and colorectal cancer risk in a cohort of women.  Int J Cancer. 2002;  97 864-7
• 103 Terry P D, Jain M, Miller A B, Howe G R, Rohan T E. Glycemic load, carbohydrate intake, and risk of colorectal cancer in women: a prospective cohort study.  J Natl Cancer Inst. 2003;  95 914-6
• 104 Terry P D, Miller A B, Rohan T E. Obesity and colorectal cancer risk in women.  Gut. 2002;  51 191-4
• 105 Tsubono Y, Otani T, Kobayashi M, Yamamoto S, Sobue T, Tsugane S. JPHC Study Group: No association between fruit or vegetable consumption and the risk of colorectal cancer in Japan.  Br J Cancer. 2005;  92 1782-4
• 106 Dam R M van, Rimm E B, Willett W C, Stampfer M J, Hu F B. Dietary patterns and risk for type 2 diabetes mellitus in U.S. men.  Ann Intern Med. 2002;  136 201-9
• 107 Voorrips L E, Goldbohm R A, Poppel G van, Sturmans F, Hermus R J, Brandt P A van den. Vegetable and fruit consumption and risks of colon and rectal cancer in a prospective cohort study: The Netherlands Cohort Study on Diet and Cancer.  Am J Epidemiol. 2000;  152 1081-92
• 108 Wei E K, Giovannucci E, Wu K, Rosner B, Fuchs C S, Willett W C, Colditz G A. Comparison of risk factors for colon and rectal cancer.  Int J Cancer. 2004;  108 433-42
• 109 Weingarten M A, Zalmanovici A, Yaphe J. Dietary calcium supplementation for preventing colorectal cancer and adenomatous polyps.  Cochrane Database Syst Rev. 2005;  CD003548
• 110 White E, Shannon J S, Patterson R E. Relationship between vitamin and calcium supplement use and colon cancer.  Cancer Epidemiol Biomarkers Prev. 1997;  6 769-774
• 111 WHO/FAO .Diet, Nutrition and the Prevention of Chronic Diseases: Report of a Joint WHO/FAO Expert Consultation. Technical Report Series, No. 916 Geneva; WHO 2003
• 112 Williams M T, Hord N G. The role of dietary factors in cancer prevention: beyond fruits and vegetables.  Nutr Clin Pract. 2005;  20 451-9
• 113 Wolters M, Ströhle A, Hahn A. Folsäure in der Prävention des kolorektalen Karzinoms.  Aktuel Ernähr Med. 2005;  30 1-12
• 114 World Cancer Research Fund, American Institute for Cancer Research .Food, nutrition and the prevention of cancer: a global perspective. Washington DC; American Institute for Cancer Research 1997
• 115 Yoon H, Benamouzig R, Little J, Francois-Collange M, Tome D. Systematic review of epidemiological studies on meat, dairy products and egg consumption and risk of colorectal adenomas.  Eur J Cancer Prev. 2000;  9 151-64

Korrespondenzadresse