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Cancer Causes & Control

, Volume 30, Issue 5, pp 527–535 | Cite as

Flavonoids and bladder cancer risk

  • Marta Rossi
  • Panagiota Strikoudi
  • Maria-Eleni Spei
  • Maria Parpinel
  • Diego Serraino
  • Maurizio Montella
  • Massimo Libra
  • Carlo La Vecchia
  • Valentina RosatoEmail author
Original Paper

Abstract

Purpose

Flavonoids have drawn attention because of their antioxidant capacity and anti-carcinogenic effect in various types of cancer. A limited number of studies has investigated their potential effect on the risk of bladder cancer, with inconsistent results.

Methods

We analyzed data from an Italian case–control study including 690 incident bladder cancer cases and 665 controls admitted to the same network of hospitals for acute, non-neoplastic, non tobacco-related diseases. Subjects were interviewed using a reproducible and validated food-frequency questionnaire. We applied data on food and beverage composition to estimate the intake of isoflavones, anthocyanidins, flavan-3-ols, flavanones, flavones and flavonols. We estimated odds ratios (ORs) through multiple logistic regression models, including terms for potential confounding factors, including tobacco smoking and total energy intake.

Results

We found an inverse association between isoflavones (OR for the highest compared to the lowest quintile of intake = 0.56, 95% CI 0.37–0.84) and flavones (OR = 0.64, 95% CI 0.44–0.95) and bladder cancer. Non-significant inverse association was found for flavan-3-ols (OR = 0.70), flavonols (OR = 0.85) and total flavonoids (OR = 0.76). The results were consistent for non-muscle-invasive and muscle-invasive bladder cancers.

Conclusions

Our data indicate an inverse association between isoflavones and flavones with respect to bladder cancer risk.

Keywords

Case–control study Bladder cancer Flavonoids Risk factors 

Notes

Acknowledgments

This work was supported by the Italian Association for Cancer Research (AIRC) (My First AIRC Grant No. 17070). V.R. was supported by a fellowship from the Italian Foundation for Cancer Research (FIRC No. 18107). We also acknowledge the Lega Italiana per la Lotta contro i Tumori Sede Centrale for the contribution on the 5/1000 Project, 2015.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10552_2019_1158_MOESM1_ESM.docx (18 kb)
Supplementary material 1 (DOCX 17 KB)

References

  1. 1.
    Burger M, Catto JW, Dalbagni G, Grossman HB, Herr H, Karakiewicz P, Kassouf W, Kiemeney LA, La Vecchia C, Shariat S, Lotan Y (2013) Epidemiology and risk factors of urothelial bladder cancer. Eur Urol 63:234–241CrossRefGoogle Scholar
  2. 2.
    Turati F, Polesel J, Di Maso M, Montella M, Libra M, Grimaldi M, Tavani A, Serraino D, La Vecchia C, Bosetti C (2015) Diabetes mellitus and the risk of bladder cancer: an Italian case–control study. Br J Cancer 113:127–130CrossRefGoogle Scholar
  3. 3.
    Bedwani R, Renganathan E, El Kwhsky F, Braga C, Abu Seif HH, Abul Azm T, Zaki A, Franceschi S, Boffetta P, La Vecchia C (1998) Schistosomiasis and the risk of bladder cancer in Alexandria, Egypt. Br J Cancer 77:1186–1189CrossRefGoogle Scholar
  4. 4.
    La Vecchia C, Negri E, D’Avanzo B, Savoldelli R, Franceschi S (1991) Genital and urinary tract diseases and bladder cancer. Cancer Res 51:629–631Google Scholar
  5. 5.
    Pelucchi C, Bosetti C, Negri E, Malvezzi M, La Vecchia C (2006) Mechanisms of disease: the epidemiology of bladder cancer. Nat Clin Pract Urol 3:327–340CrossRefGoogle Scholar
  6. 6.
    D’Avanzo B, La Vecchia C, Negri E, Decarli A, Benichou J (1995) Attributable risks for bladder cancer in northern Italy. Ann Epidemiol 5:427–431CrossRefGoogle Scholar
  7. 7.
    Turati F, Bosetti C, Polesel J, Serraino D, Montella M, Libra M, Facchini G, Ferraroni M, Tavani A, La Vecchia C, Negri E (2017) Family history of cancer and the risk of bladder cancer: A case–control study from Italy. Cancer Epidemiol 48:29–35CrossRefGoogle Scholar
  8. 8.
    Smith AH, Marshall G, Roh T, Ferreccio C, Liaw J, Steinmaus C (2018) Lung, bladder, and kidney cancer mortality 40 years after arsenic exposure reduction. J Natl Cancer Inst 110:241–249CrossRefGoogle Scholar
  9. 9.
    World Cancer Research Fund International/American Institute for Cancer Research (2015) Continuous update project report: diet, nutrition, physical activity and bladder cancerGoogle Scholar
  10. 10.
    Liu H, Wang XC, Hu GH, Guo ZF, Lai P, Xu L, Huang TB, Xu YF (2015) Fruit and vegetable consumption and risk of bladder cancer: an updated meta-analysis of observational studies. Eur J Cancer Prev 24:508–516CrossRefGoogle Scholar
  11. 11.
    Yao B, Yan Y, Ye X, Fang H, Xu H, Liu Y, Li S, Zhao Y (2014) Intake of fruit and vegetables and risk of bladder cancer: a dose-response meta-analysis of observational studies. Cancer Causes Control 25:1645–1658CrossRefGoogle Scholar
  12. 12.
    La Vecchia C, Negri E (1996) Nutrition and bladder cancer. Cancer Causes Control 7:95–100CrossRefGoogle Scholar
  13. 13.
    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 81:230S–242SCrossRefGoogle Scholar
  14. 14.
    Rossi M, Negri E, Talamini R, Bosetti C, Parpinel M, Gnagnarella P, Franceschi S, Dal Maso L, Montella M, Giacosa A, La Vecchia C (2006) Flavonoids and colorectal cancer in Italy. Cancer Epidemiol Biomarkers Prev 15:1555–1558CrossRefGoogle Scholar
  15. 15.
    Rossi M, Bosetti C, Negri E, Lagiou P, La Vecchia C (2010) Flavonoids, proanthocyanidins, and cancer risk: a network of case–control studies from Italy. Nutr Cancer 62:871–877CrossRefGoogle Scholar
  16. 16.
    Rossi M, Rosato V, Bosetti C, Lagiou P, Parpinel M, Bertuccio P, Negri E, La Vecchia C (2010) Flavonoids, proanthocyanidins, and the risk of stomach cancer. Cancer Causes Control 21:1597–1604CrossRefGoogle Scholar
  17. 17.
    Batra P, Sharma AK (2013) Anti-cancer potential of flavonoids: recent trends and future perspectives. 3 Biotech 3:439–459CrossRefGoogle Scholar
  18. 18.
    USDA database for the (2003) Flavonoid content of selected foods. USDA, BeltsvilleGoogle Scholar
  19. 19.
    Singh AV, Franke AA, Blackburn GL, Zhou JR (2006) Soy phytochemicals prevent orthotopic growth and metastasis of bladder cancer in mice by alterations of cancer cell proliferation and apoptosis and tumor angiogenesis. Cancer Res 66:1851–1858CrossRefGoogle Scholar
  20. 20.
    Zamora-Ros R, Sacerdote C, Ricceri F, Weiderpass E, Roswall N, Buckland G, St-Jules DE, Overvad K, Kyro C, Fagherazzi G, Kvaskoff M, Severi G, Chang-Claude J, Kaaks R, Nothlings U, Trichopoulou A, Naska A, Trichopoulos D, Palli D, Grioni S, Mattiello A, Tumino R, Gram IT, Engeset D, Huerta JM, Molina-Montes E, Arguelles M, Amiano P, Ardanaz E, Ericson U, Lindkvist B, Nilsson LM, Kiemeney LA, Ros M, Bueno-de-Mesquita HB, Peeters PH, Khaw KT, Wareham NJ, Knaze V, Romieu I, Scalbert A, Brennan P, Wark P, Vineis P, Riboli E, Gonzalez CA (2014) Flavonoid and lignan intake in relation to bladder cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Br J Cancer 111:1870–1880CrossRefGoogle Scholar
  21. 21.
    Garcia R, Gonzalez CA, Agudo A, Riboli E (1999) High intake of specific carotenoids and flavonoids does not reduce the risk of bladder cancer. Nutr Cancer 35:212–214CrossRefGoogle Scholar
  22. 22.
    Sun CL, Yuan JM, Arakawa K, Low SH, Lee HP, Yu MC (2002) Dietary soy and increased risk of bladder cancer: the Singapore Chinese health study. Cancer Epidemiol Biomarkers Prev 11:1674–1677Google 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 13:373–382CrossRefGoogle Scholar
  24. 24.
    Sun CL, Yuan JM, Wang XL, Gao YT, Ross RK, Yu MC (2004) Dietary soy and increased risk of bladder cancer: a prospective cohort study of men in Shanghai, China. Int J Cancer 112:319–323CrossRefGoogle Scholar
  25. 25.
    Turati F, Bosetti C, Polesel J, Zucchetto A, Serraino D, Montella M, Libra M, Galfano A, La Vecchia C, Tavani A (2015) Coffee, tea, cola, and bladder cancer risk: dose and time relationships. Urology 86:1179–1184CrossRefGoogle Scholar
  26. 26.
    Shivappa N, Hebert JR, Rosato V, Rossi M, Libra M, Montella M, Serraino D, La Vecchia C (2017) Dietary inflammatory index and risk of bladder cancer in a large Italian case–control study. Urology 100:84–89CrossRefGoogle Scholar
  27. 27.
    Decarli A, Franceschi S, Ferraroni M, Gnagnarella P, Parpinel MT, La Vecchia C, Negri E, Salvini S, Falcini F, Giacosa A (1996) Validation of a food-frequency questionnaire to assess dietary intakes in cancer studies in Italy. Results for specific nutrients. Ann Epidemiol 6:110–118CrossRefGoogle Scholar
  28. 28.
    Franceschi S, Negri E, Salvini S, Decarli A, Ferraroni M, Filiberti R, Giacosa A, Talamini R, Nanni O, Panarello G et al (1993) Reproducibility of an Italian food frequency questionnaire for cancer studies: results for specific food items. Eur J Cancer 29A:2298–2305CrossRefGoogle Scholar
  29. 29.
    Iowa State University database on the isoflavone content of foods, Release 1.3. Beltsville, MD: USDA (2002)Google Scholar
  30. 30.
    Liggins J, Bluck LJ, Runswick S, Atkinson C, Coward WA, Bingham SA (2000) Daidzein and genistein content of fruits and nuts. J Nutr Biochem 11:326–331CrossRefGoogle Scholar
  31. 31.
    Liggins J, Bluck LJ, Runswick S, Atkinson C, Coward WA, Bingham SA (2000) Daidzein and genistein contents of vegetables. Br J Nutr 84:717–725Google Scholar
  32. 32.
    Liggins J, Mulligan A, Runswick S, Bingham SA (2002) Daidzein and genistein content of cereals. Eur J Clin Nutr 56:961–966CrossRefGoogle Scholar
  33. 33.
    Gnagnarella P, Parpinel M, Salvini S, Franceschi S, Palli D, Boyle P (2004) The update of the Italian food composition database. J Food Comp Anal 17:509–522CrossRefGoogle Scholar
  34. 34.
    Willett W, Stampfer MJ (1986) Total energy intake: implications for epidemiologic analyses. Am J Epidemiol 124:17–27CrossRefGoogle Scholar
  35. 35.
    Aune D, De Stefani E, Ronco A, Boffetta P, Deneo-Pellegrini H, Acosta G, Mendilaharsu M (2009) Legume intake and the risk of cancer: a multisite case–control study in Uruguay. Cancer Causes Control 20:1605–1615CrossRefGoogle Scholar
  36. 36.
    Schabath MB, Spitz MR, Lerner SP, Pillow PC, Hernandez LM, Delclos GL, Grossman HB, Wu X (2005) Case–control analysis of dietary folate and risk of bladder cancer. Nutr Cancer 53:144–151CrossRefGoogle Scholar
  37. 37.
    Park OJ, Surh YJ (2004) Chemopreventive potential of epigallocatechin gallate and genistein: evidence from epidemiological and laboratory studies. Toxicol Lett 150:43–56CrossRefGoogle Scholar
  38. 38.
    Su SJ, Yeh TM, Lei HY, Chow NH (2000) The potential of soybean foods as a chemoprevention approach for human urinary tract cancer. Clin Cancer Res 6:230–236Google Scholar
  39. 39.
    Wang Y, Wang H, Zhang W, Shao C, Xu P, Shi CH, Shi JG, Li YM, Fu Q, Xue W, Lei YH, Gao JY, Wang JY, Gao XP, Li JQ, Yuan JL, Zhang YT (2013) Genistein sensitizes bladder cancer cells to HCPT treatment in vitro and in vivo via ATM/NF-kappaB/IKK pathway-induced apoptosis. PLoS ONE 8:e50175CrossRefGoogle Scholar
  40. 40.
    Theodorescu D, Laderoute KR, Calaoagan JM, Guilding KM (1998) Inhibition of human bladder cancer cell motility by genistein is dependent on epidermal growth factor receptor but not p21ras gene expression. Int J Cancer 78:775–782CrossRefGoogle Scholar
  41. 41.
    Su S, Lai M, Yeh T, Chow N (2001) Overexpression of HER-2/neu enhances the sensitivity of human bladder cancer cells to urinary isoflavones. Eur J Cancer 37:1413–1418CrossRefGoogle Scholar
  42. 42.
    Su SJ, Yeh TM, Chuang WJ, Ho CL, Chang KL, Cheng HL, Liu HS, Cheng HL, Hsu PY, Chow NH (2005) The novel targets for anti-angiogenesis of genistein on human cancer cells. Biochem Pharmacol 69:307–318CrossRefGoogle Scholar
  43. 43.
    Russo M, Russo GL, Daglia M, Kasi PD, Ravi S, Nabavi SF, Nabavi SM (2016) Understanding genistein in cancer: the “good” and the “bad” effects: a review. Food Chem 196:589–600CrossRefGoogle Scholar
  44. 44.
    Kilani-Jaziri S, Frachet V, Bhouri W, Ghedira K, Chekir-Ghedira L, Ronot X (2012) Flavones inhibit the proliferation of human tumor cancer cell lines by inducing apoptosis. Drug Chem Toxicol 35:1–10CrossRefGoogle Scholar
  45. 45.
    Su CC, Chen GW, Yeh CC, Yang MD, Hung CF, Chung JG (2003) Luteolin induces N-acetylation and DNA adduct of 2-aminofluorene accompanying N-acetyltransferase activity and gene expression in human bladder cancer T24 cell line. Anticancer Res 23:355–362Google Scholar
  46. 46.
    Cherng JM, Shieh DE, Chiang W, Chang MY, Chiang LC (2007) Chemopreventive effects of minor dietary constituents in common foods on human cancer cells. Biosci Biotechnol Biochem 71:1500–1504CrossRefGoogle Scholar
  47. 47.
    Shi MD, Shiao CK, Lee YC, Shih YW (2015) Apigenin, a dietary flavonoid, inhibits proliferation of human bladder cancer T-24 cells via blocking cell cycle progression and inducing apoptosis. Cancer Cell Int 15:33CrossRefGoogle Scholar
  48. 48.
    Liu Q, Chen X, Yang G, Min X, Deng M (2011) Apigenin inhibits cell migration through MAPK pathways in human bladder smooth muscle cells. Biocell 35:71–79Google Scholar
  49. 49.
    Zhu Y, Mao Y, Chen H, Lin Y, Hu Z, Wu J, Xu X, Xu X, Qin J, Xie L (2013) Apigenin promotes apoptosis, inhibits invasion and induces cell cycle arrest of T24 human bladder cancer cells. Cancer Cell Int 13:54CrossRefGoogle Scholar
  50. 50.
    Xu C, Zeng XT, Liu TZ, Zhang C, Yang ZH, Li S, Chen XY (2015) Fruits and vegetables intake and risk of bladder cancer: a PRISMA-compliant systematic review and dose-response meta-analysis of prospective cohort studies. Medicine 94:e759CrossRefGoogle Scholar
  51. 51.
    Park SY, Ollberding NJ, Woolcott CG, Wilkens LR, Henderson BE, Kolonel LN (2013) Fruit and vegetable intakes are associated with lower risk of bladder cancer among women in the Multiethnic Cohort Study. J Nutr 143:1283–1292CrossRefGoogle Scholar
  52. 52.
    Al-Zalabani AH, Stewart KF, Wesselius A, Schols AM, Zeegers MP (2016) Modifiable risk factors for the prevention of bladder cancer: a systematic review of meta-analyses. Eur J Epidemiol 31:811–851CrossRefGoogle Scholar
  53. 53.
    Dugue PA, Hodge AM, Brinkman MT, Bassett JK, Shivappa N, Hebert JR, Hopper JL, English DR, Milne RL, Giles GG (2016) Association between selected dietary scores and the risk of urothelial cell carcinoma: a prospective cohort study. Int J Cancer 139:1251–1260CrossRefGoogle Scholar
  54. 54.
    De Stefani E, Boffetta P, Ronco AL, Deneo-Pellegrini H, Acosta G, Mendilaharsu M (2008) Dietary patterns and risk of bladder cancer: a factor analysis in Uruguay. Cancer Causes Control 19:1243–1249CrossRefGoogle Scholar
  55. 55.
    Finglas PM, Berry R, Astley S (2014) Assessing and improving the quality of food composition databases for nutrition and health applications in Europe: the contribution of EuroFIR. Adv Nutr 5:608S–614SCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Clinical Sciences and Community HealthUniversità degli Studi di MilanoMilanItaly
  2. 2.Department of Nutrition and Dietetics, Faculty of Agriculture Technology, Food Technology and NutritionAlexander Technological Educational Institution of ThessalonikiSindos, ThessalonikiGreece
  3. 3.Department of Hygiene, Epidemiology, and Medical Statistics, School of MedicineNational and Kapodistrian University of AthensGoudi, AthensGreece
  4. 4.Department of MedicineUniversità degli Studi di UdineUdineItaly
  5. 5.Cancer Epidemiology UnitIstituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Centro di Riferimento OncologicoAviano (PN)Italy
  6. 6.Unit of EpidemiologyIstituto Nazionale Tumori Fondazione G. PascaleNapoliItaly
  7. 7.Section of Oncologic, Clinic and General Pathology, Department of Biomedical & Biotechnological SciencesUniversità degli Studi di CataniaCataniaItaly
  8. 8.Unit of Medical Statistics and BiometryFondazione IRCCS Istituto Nazionale dei Tumori di MilanoMilanoItaly

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