Cancer Causes & Control

, Volume 24, Issue 3, pp 549–557 | Cite as

Association between habitual dietary flavonoid and lignan intake and colorectal cancer in a Spanish case–control study (the Bellvitge Colorectal Cancer Study)

  • Raul Zamora-RosEmail author
  • Carla Not
  • Elisabeth Guinó
  • Leila Luján-Barroso
  • Raul M. García
  • Sebastiano Biondo
  • Ramón Salazar
  • Victor Moreno
Original paper



Flavonoid-rich foods, such as fruits, vegetables, and tea, may have a protective effect upon colorectal cancer. However, current epidemiological evidence for a protective effect of flavonoid intake upon colorectal cancer is promising but not conclusive.


To examine the relation between dietary flavonoid and lignan intakes and the risk of colorectal cancer within a Spanish population.


Data from the Bellvitge Colorectal Cancer Study, a case–control study (424 cases with incident colorectal cancer and 401 hospital-based controls), were used. A reproducible and validated food frequency questionnaire was administered in personal interviews. An ad hoc food composition database on flavonoids and lignans was compiled, mainly using data from the US Department of Agriculture and Phenol-Explorer databases. Adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) were estimated using unconditional logistic regression models.


An inverse association was found between intake of total flavonoids (OR, 0.59; 95 % CI, 0.35–0.99 for the highest vs. the lowest quartile; p for trend = 0.04), lignans (OR, 0.59; 95 % CI, 0.34–0.99; p for trend = 0.03), and some individual flavonoid subgroups (flavones, proanthocyanidins) and the risk of colorectal cancer. Separate analyses by cancer site showed similar results.


Intake of total dietary flavonoids (particularly certain flavonoid subgroups) and lignans was inversely associated with colorectal cancer risk in a Spanish population.


Flavonoids Lignans Colorectal cancer Case–control study 



European Prospective Investigation into Cancer and Nutrition


Food composition database




US Department of Agriculture



This study has received financial support from the Spanish Instituto de Salud Carlos III RTICCC RD06/0020, CIBERESP CB07/02/2005 and grants PI08-1359, PI08-1635, PS09-1037) and also from the Spanish Association Against Cancer (AECC) Scientific Foundation, the Catalan Government DURSI grant 2009SGR1489, and the European Commission grants FOOD-CT-2006-036224-HIWATE and FP7-COOP-Health-2007-B HiPerDART. R. Z. R. is thankful for a postdoctoral “Sara Borrell” program (CD09/00133) from the MEC and Instituto de Salud Carlos III.

Conflict of interest

The authors are not aware of any conflict of interest.


  1. 1.
    World Research Cancer Fund, American Institute for Cancer Research (2007) Food, nutrition, physical activity and the prevention of cancer: a global perspective. American Institute for Cancer Research, WashingtonGoogle Scholar
  2. 2.
    Perez-Jimenez J, Neveu V, Vos F, Scalbert A (2010) Identification of the 100 richest dietary sources of polyphenols: an application of the Phenol-Explorer database. Eur J Clin Nutr 64(Suppl 3):S112–S120PubMedCrossRefGoogle Scholar
  3. 3.
    de Kok TM, van Breda SG, Manson MM (2008) Mechanisms of combined action of different chemopreventive dietary compounds: a review. Eur J Nutr 47(Suppl 2):51–59PubMedCrossRefGoogle Scholar
  4. 4.
    Kampa M, Nifli AP, Notas G, Castanas E (2007) Polyphenols and cancer cell growth. Rev Physiol Biochem Pharmacol 159:79–113PubMedCrossRefGoogle Scholar
  5. 5.
    Thomasset SC, Berry DP, Garcea G, Marczylo T, Steward WP, Gescher AJ (2007) Dietary polyphenolic phytochemicals-promising cancer chemopreventive agents in humans? Int J Cancer 120:451–458PubMedCrossRefGoogle Scholar
  6. 6.
    Curtis PJ, Sampson M, Potter J, Dhatariya K, Kroon PA, Cassidy A (2012) Chronic ingestion of flavan-3-ols and isoflavones improves insulin sensitivity and lipoprotein status and attenuates estimated 10-year CVD risk in medicated postmenopausal women with type 2 diabetes: a 1-year, double-blind, randomized, controlled trial. Diabetes Care 35:226–232PubMedCrossRefGoogle Scholar
  7. 7.
    Gonzalez-Gallego J, Garcia-Mediavilla MV, Sanchez-Campos S, Tunon MJ (2010) Fruit polyphenols, immunity and inflammation. Br J Nutr 104(Suppl 3):S15–S27PubMedCrossRefGoogle Scholar
  8. 8.
    Sun CL, Yuan JM, Koh WP, Yu MC (2006) Green tea, black tea and colorectal cancer risk: a meta-analysis of epidemiologic studies. Carcinogenesis 27:1301–1309PubMedCrossRefGoogle Scholar
  9. 9.
    Akhter M, Iwasaki M, Yamaji T, Sasazuki S, Tsugane S (2009) Dietary isoflavone and the risk of colorectal adenoma: a case-control study in Japan. Br J Cancer 100:1812–1816PubMedCrossRefGoogle Scholar
  10. 10.
    Theodoratou E, Kyle J, Cetnarskyj R et al (2007) Dietary flavonoids and the risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev 16:684–693PubMedCrossRefGoogle Scholar
  11. 11.
    Rossi M, Negri E, Talamini R et al (2006) Flavonoids and colorectal cancer in Italy. Cancer Epidemiol Biomarkers Prev 15:1555–1558PubMedCrossRefGoogle Scholar
  12. 12.
    Rossi M, Negri E, Parpinel M et al (2010) Proanthocyanidins and the risk of colorectal cancer in Italy. Cancer Causes Control 21:243–250PubMedCrossRefGoogle Scholar
  13. 13.
    Kyle JAM, Sharp L, Little J, Duthie GG, McNeill G (2010) Dietary flavonoid intake and colorectal cancer: a case-control study. Br J Nutr 103:429–436PubMedCrossRefGoogle Scholar
  14. 14.
    Cotterchio M, Boucher BA, Manno M, Gallinger S, Okey A, Harper P (2006) Dietary phytoestrogen intake is associated with reduced colorectal cancer risk. J Nutr 136:3046–3053PubMedGoogle Scholar
  15. 15.
    Bobe G, Sansbury LB, Albert PS et al (2008) Dietary flavonoids and colorectal adenoma recurrence in the Polyp Prevention Trial. Cancer Epidemiol Biomarkers Prev 17:1344–1353PubMedCrossRefGoogle Scholar
  16. 16.
    Wang L, Lee IM, Zhang SM, Blumberg JB, Buring JE, Sesso HD (2009) Dietary intake of selected flavonols, flavones, and flavonoid-rich foods and risk of cancer in middle-aged and older women. Am J Clin Nutr 89:905–912PubMedCrossRefGoogle Scholar
  17. 17.
    Akhter M, Inoue M, Kurahashi N, Iwasaki M, Sasazuki S, Tsugane S (2008) Dietary soy and isoflavone intake and risk of colorectal cancer in the Japan public health center-based prospective study. Cancer Epidemiol Biomarkers Prev 17:2128–2135PubMedCrossRefGoogle Scholar
  18. 18.
    Mursu J, Nurmi T, Tuomainen TP, Salonen JT, Pukkala E, Voutilainen S (2008) Intake of flavonoids and risk of cancer in Finnish men: the Kuopio Ischaemic Heart Disease Risk Factor Study. Int J Cancer 123:660–663PubMedCrossRefGoogle Scholar
  19. 19.
    Lin J, Zhang SM, Wu K, Willett WC, Fuchs CS, Giovannucci E (2006) Flavonoid intake and colorectal cancer risk in men and women. Am J Epidemiol 164:644–651PubMedCrossRefGoogle Scholar
  20. 20.
    Knekt P, Kumpulainen J, Jarvinen R et al (2002) Flavonoid intake and risk of chronic diseases. Am J Clin Nutr 76:560–568PubMedGoogle Scholar
  21. 21.
    Hirvonen T, Virtamo J, Korhonen P, Albanes D, Pietinen P (2001) Flavonol and flavone intake and the risk of cancer in male smokers (Finland). Cancer Causes Control 12:789–796PubMedCrossRefGoogle Scholar
  22. 22.
    Knekt P, Jarvinen R, Seppanen R et al (1997) Dietary flavonoids and the risk of lung cancer and other malignant neoplasms. Am J Epidemiol 146:223–230PubMedCrossRefGoogle Scholar
  23. 23.
    Arts IC, Jacobs DR Jr, Gross M, Harnack LJ, Folsom AR (2002) Dietary catechins and cancer incidence among postmenopausal women: the Iowa Women’s Health Study (United States). Cancer Causes Control 13:373–382PubMedCrossRefGoogle Scholar
  24. 24.
    Ward HA, Kuhnle GG, Mulligan AA, Lentjes MA, Luben RN, Khaw KT (2010) Breast, colorectal, and prostate cancer risk in the European Prospective Investigation into Cancer and Nutrition-Norfolk in relation to phytoestrogen intake derived from an improved database. Am J Clin Nutr 91:440–448PubMedCrossRefGoogle Scholar
  25. 25.
    Ward H, Chapelais G, Kuhnle GG, Luben R, Khaw KT, Bingham S (2008) Lack of prospective associations between plasma and urinary phytoestrogens and risk of prostate or colorectal cancer in the European Prospective into Cancer-Norfolk study. Cancer Epidemiol Biomarkers Prev 17:2891–2894PubMedCrossRefGoogle Scholar
  26. 26.
    Manach C, Williamson G, Morand C, Scalbert A, Remesy C (2005) Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am J Clin Nutr 81(Suppl 1):230S–242SPubMedGoogle Scholar
  27. 27.
    Landi S, Bottari F, Gemignani F et al (2007) Interleukin-4 and interleukin-4 receptor polymorphisms and colorectal cancer risk. Eur J Cancer 43:762–768PubMedCrossRefGoogle Scholar
  28. 28.
    EPIC Group of Spain (1997) Relative validity and reproducibility of a diet history questionnaire in Spain. I. Foods. Int J Epidemiol 26(Suppl 1):S91–S99Google Scholar
  29. 29.
    EPIC Group of Spain (1997) Relative validity and reproducibility of a diet history questionnaire in Spain. II. Nutrients. Int J Epidemiol 26(Suppl 1):S100–S109Google Scholar
  30. 30.
    Slimani N, Deharveng G, Unwin I et al (2007) The EPIC nutrient database project (ENDB): a first attempt to standardize nutrient databases across the 10 European countries participating in the EPIC study. Eur J Clin Nutr 61:1037–1056PubMedCrossRefGoogle Scholar
  31. 31.
    Knaze V, Zamora-Ros R, Luján-Barroso L et al. (2011) Intake estimation of total and individual flavan-3-ols, proanthocyanidins and theaflavins, their food sources and determinants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Br J Nutr. doi: 10.1017/S0007114511006386
  32. 32.
    Zamora-Ros R, Knaze V, Luján-Barroso L et al (2011) Estimation of the intake of anthocyanidins and their food sources in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Br J Nutr 106:1090–1099PubMedCrossRefGoogle Scholar
  33. 33.
    Zamora-Ros R, Knaze V, Luján-Barroso L, Slimani N, Romieu I, Fedirko V (2011) Estimated dietary intakes of flavonols, flavanones and flavones in the European Prospective Investigation into Cancer and Nutrition (EPIC) 24-h dietary recall cohort. Br J Nutr 106:1915–1925PubMedCrossRefGoogle Scholar
  34. 34.
    Zamora-Ros R, Knaze V, Luján-Barroso L et al. (2012) Dietary intakes and food sources of phytoestrogens in the European Prospective Investigation into Cancer and Nutrition (EPIC) 24-hour dietary recall cohort. Eur J Clin Nutr. doi: 10.1038/ejcn.2012.36
  35. 35.
    U.S. Department of Agriculture (2007) USDA database for the flavonoid content of selected foods. Release 2.1 ed. U.S. Department of Agriculture, BeltsvilleGoogle Scholar
  36. 36.
    U.S. Department of Agriculture (2008) USDA database for the isoflavone content of selected foods. Release 2.0 ed. U.S. Department of Agriculture, BeltsvilleGoogle Scholar
  37. 37.
    U.S. Department of Agriculture (2004) USDA database for the proanthocyanidin content of selected foods. U.S. Department of Agriculture, BeltsvilleGoogle Scholar
  38. 38.
    Neveu V, Perez-Jimenez J, Vos F et al (2010) Phenol-Explorer: an online comprehensive database on polyphenol contents in foods. Database (Oxf) 2010:bap024CrossRefGoogle Scholar
  39. 39.
    Willett W, Sampfer MJ (1986) Total energy intake: implications for epidemiological analyses. Am J Epidemiol 124:17–27PubMedGoogle Scholar
  40. 40.
    Pierini R, Gee JM, Belshaw NJ, Johnson IT (2008) Flavonoids and intestinal cancers. Br J Nutr 99(Suppl. 1):ES53–ES59PubMedGoogle Scholar
  41. 41.
    Hoensch HP, Kirch W (2005) Potential role of flavonoids in the prevention of intestinal neoplasia: a review of their mode of action and their clinical perspectives. Int J Gastrointest Cancer 35:187–195PubMedCrossRefGoogle Scholar
  42. 42.
    Williamson G, Clifford MN (2010) Colonic metabolites of berry polyphenols: the missing link to biological activity? Br J Nutr 104(Suppl 3):S48–S66PubMedCrossRefGoogle Scholar
  43. 43.
    Kramer F, Johnson IT, Doleman JF, Lund EK (2009) A comparison of the effects of soya isoflavonoids and fish oil on cell proliferation, apoptosis and the expression of oestrogen receptors alpha and beta in the mammary gland and colon of the rat. Br J Nutr 102:29–36PubMedCrossRefGoogle Scholar
  44. 44.
    Bielecki A, Roberts J, Mehta R, Raju J (2011) Estrogen receptor-beta mediates the inhibition of DLD-1 human colon adenocarcinoma cells by soy isoflavones. Nutr Cancer 63:139–150PubMedGoogle Scholar
  45. 45.
    Schleipen B, Hertrampf T, Fritzemeier K et al (2011) ER{beta}-specific agonists and genistein inhibit proliferation and induce apoptosis in the large and small intestine. Carcinogenesis 32:1675–1683PubMedCrossRefGoogle Scholar
  46. 46.
    Breslow NE, Day NE (1980) Statistical methods in cancer research. Volume I—the analysis of case-control studies. IARC Sci Publ 32:5–338PubMedGoogle Scholar
  47. 47.
    EPIC Group of Spain (1997) Relative validity and reproducibility of a diet history questionnaire in Spain. III. Biochemical markers. Int J Epidemiol 26(Suppl 1):S110–S117Google Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Raul Zamora-Ros
    • 1
    Email author
  • Carla Not
    • 1
  • Elisabeth Guinó
    • 2
    • 3
  • Leila Luján-Barroso
    • 1
  • Raul M. García
    • 1
  • Sebastiano Biondo
    • 4
    • 5
  • Ramón Salazar
    • 3
    • 6
  • Victor Moreno
    • 2
    • 3
    • 4
  1. 1.Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research ProgrammeCatalan Institute of Oncology (ICO-IDIBELL)L’Hospitalet de Llobregat, BarcelonaSpain
  2. 2.Biomarkers and Susceptibility Unit, Cancer Prevention and Control ProgramCatalan Institute of Oncology (ICO-IDIBELL)BarcelonaSpain
  3. 3.CIBERESPBarcelonaSpain
  4. 4.Department of Clinical Sciences, Faculty of MedicineUniversity of BarcelonaBarcelonaSpain
  5. 5.General Surgery ServiceBellvitge University Hospital (HUB-IDIBELL)BarcelonaSpain
  6. 6.Oncology ServiceCatalan Institute of Oncology (ICO-IDIBELL)BarcelonaSpain

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