Cancer Causes & Control

, Volume 25, Issue 12, pp 1645–1658 | Cite as

Intake of fruit and vegetables and risk of bladder cancer: a dose–response meta-analysis of observational studies

  • Baodong Yao
  • Yujie Yan
  • Xianwu Ye
  • Hong Fang
  • Huilin Xu
  • Yinan Liu
  • Sheran Li
  • Yanping Zhao
Original paper



Observational studies suggest an association between fruit and vegetables intake and risk of bladder cancer, but the results are controversial.


We therefore summarized the evidence from observational studies in categorical, linear, and nonlinear, dose–response meta-analysis. Pertinent studies were identified by searching EMBASE and PubMed from their inception to August 2013.


Thirty-one observational studies involving 12,610 cases and 1,121,649 participants were included. The combined rate ratio (RR, 95 % CI) of bladder cancer for the highest versus lowest intake was 0.83 (0.69–0.99) for total fruit and vegetables, 0.81 (0.70–0.93) for total vegetables, 0.77 (0.69–0.87) for total fruit, 0.84 (0.77–0.91) for cruciferous vegetables, 0.79 (0.68–0.91) for citrus fruits, and 0.74 (0.66–0.84) for yellow–orange vegetables. Subgroup analysis showed study design and gender as possible sources of heterogeneity. A nonlinear relationship was found of citrus fruits intake with risk of bladder cancer (P for nonlinearity = 0.018), and the RRs (95 % CI) of bladder cancer were 0.87 (0.78–0.96), 0.80 (0.67–0.94), 0.79 (0.66–0.94), 0.79 (0.65–0.96), and 0.79 (0.64–0.99) for 30, 60, 90, 120, and 150 g/day. A nonlinear relationship was also found of yellow–orange vegetable intake with risk of bladder cancer risk (P for nonlinearity = 0.033). Some evidence of publication bias was observed for fruit, citrus fruits, and yellow–orange vegetables.


This meta-analysis supports the hypothesis that intakes of fruit and vegetables may reduce the risk of bladder cancer. Future well-designed studies are required to confirm this finding.


Bladder cancer Bladder neoplasms Meta-analysis Fruit Vegetable 


Conflict of interest

No conflict of interest existed for any of the authors.

Supplementary material

10552_2014_469_MOESM1_ESM.doc (71 kb)
Supplementary material 1 (DOC 71 kb)


  1. 1.
    World Cancer Research Fund/American Institute for Cancer Research (2007) Food, nutrition, physical activity, and the prevention of cancer: a global perspective. AICR, WashingtonGoogle Scholar
  2. 2.
    Siegel R, Naishadham D, Jemal A (2013) Cancer statistics, 2013. CA Cancer J Clin 63:11–30PubMedCrossRefGoogle Scholar
  3. 3.
    Freedman ND, Silverman DT, Hollenbeck AR, Schatzkin A, Abnet CC (2011) Association between smoking and risk of bladder cancer among men and women. JAMA 306:737–745PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Report of an IARC Working Group, Althouse R, Huff J, Tomatis L, Wllbourn J (1980) An evaluation of chemicals and industrial processes associated with cancer in humans based on human and animal data: IARC monographs volumes 1 to 20. Cancer Res 40:1–12PubMedGoogle Scholar
  5. 5.
    Badawi AF, Mostafa MH, Probert A, O’Connor PJ (1995) Role of schistosomiasis in human bladder cancer: evidence of association, aetiological factors, and basic mechanisms of carcinogenesis. Eur J Cancer Prev 4:45–59PubMedCrossRefGoogle Scholar
  6. 6.
    Steinmetz KA, Potter JD (1991) Vegetables, fruit, and cancer. I. Epidemiology. Cancer Causes Control 2:325–357PubMedCrossRefGoogle Scholar
  7. 7.
    Balbi JC, Larrinaga MT, De Stefani E, Mendilaharsu M, Ronco AL, Boffetta P, Brennan P (2001) Foods and risk of bladder cancer: a case–control study in Uruguay. Eur J Cancer Prev 10:453–458PubMedCrossRefGoogle Scholar
  8. 8.
    Castelao JE, Yuan JM, Gago-Dominguez M, Skipper PL, Tannenbaum SR, Chan KK, Watson MA, Bell DA, Coetzee GA, Ross RK, Yu MC (2004) Carotenoids/vitamin C and smoking-related bladder cancer. Int J Cancer 110:417–423PubMedCrossRefGoogle Scholar
  9. 9.
    Nagano J, Kono S, Preston DL, Moriwaki H, Sharp GB, Koyama K, Mabuchi K (2000) Bladder-cancer incidence in relation to vegetable and fruit consumption: a prospective study of atomic-bomb survivors. Int J Cancer 86:132–138PubMedCrossRefGoogle Scholar
  10. 10.
    Wu JW, Cross AJ, Baris D, Ward MH, Karagas MR, Johnson A, Schwenn M, Cherala S, Colt JS, Cantor KP, Rothman N, Silverman DT, Sinha R (2012) Dietary intake of meat, fruits, vegetables, and selective micronutrients and risk of bladder cancer in the New England region of the United States. Br J Cancer 106:1891–1898PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Isa F, Xie LP, Hu Z, Zhong Z, Hemelt M, Reulen RC, Wong YC, Tam PC, Yang K, Chai C, Zeng X, Deng Y, Zhong WD, Zeegers MP (2013) Dietary consumption and diet diversity and risk of developing bladder cancer: results from the South and East China case–control study. Cancer Causes Control 24:885–895PubMedCrossRefGoogle Scholar
  12. 12.
    Ros MM, Bueno-de-Mesquita HB, Kampman E, Büchner FL, Aben KK, Egevad L, Overvad K, Tjønneland A, Roswall N, Clavel-Chapelon F, Boutron-Ruault MC, Morois S, Kaaks R, Teucher B, Weikert S, von Ruesten A, Trichopoulou A, Naska A, Benetou V, Saieva C, Pala V, Ricceri F, Tumino R, Mattiello A, Peeters PH, van Gils CH, Gram IT, Engeset D, Chirlaque MD, Ardanazx E, Rodríguez L, Amanio P, Gonzalez CA, Sánchez MJ, Ulmert D, Ernström R, Ljungberg B, Allen NE, Key TJ, Khaw KT, Wareham N, Slimani N, Romieu I, Kiemeney LA, Riboli E (2012) Fruit and vegetable consumption and risk of aggressive and non-aggressive urothelial cell carcinomas in the European Prospective Investigation into Cancer and Nutrition. Eur J Cancer 48:3267–3277PubMedCrossRefGoogle Scholar
  13. 13.
    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 143:1283–1292PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Brinkman M, Zeegers MP (2008) Nutrition, total fluid and bladder cancer. Scand J Urol Nephrol Suppl 218:25–36PubMedCrossRefGoogle Scholar
  15. 15.
    Aune D, Lau R, Chan DS, Vieira R, Greenwood DC, Kampman E, Norat T (2011) Nonlinear reduction in risk for colorectal cancer by fruit and vegetable intake based on meta-analysis of prospective studies. Gastroenterology 141:106–118PubMedCrossRefGoogle Scholar
  16. 16.
    Liu J, Wang J, Leng Y, Lv C (2013) Intake of fruit and vegetables and risk of esophageal squamous cell carcinoma: a meta-analysis of observational studies. Int J Cancer 133:473–485PubMedCrossRefGoogle Scholar
  17. 17.
    Dauchet L, Amouyel P, Hercberg S, Dallongeville J (2006) Fruit and vegetable consumption and risk of coronary heart disease: a meta-analysis of cohort studies. J Nutr 136:2588–2593PubMedGoogle Scholar
  18. 18.
    Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558PubMedCrossRefGoogle Scholar
  19. 19.
    Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Tobias A (1999) Assessing the influence of a single study in the meta-analysis estimate. Stata Tech Bull 47:15–17Google Scholar
  22. 22.
    Orsini N, Li R, Wolk A, Khudyakov P, Spiegelman D (2012) Meta-analysis for linear and nonlinear dose–response relations: examples, an evaluation of approximations, and software. Am J Epidemiol 175:66–73PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Durrleman S, Simon R (1989) Flexible regression models with cubic splines. Stat Med 8:551–561PubMedCrossRefGoogle Scholar
  24. 24.
    Orsini N, Bellocco R, Greenland S (2006) Generalized least squares for trend estimation of summarized dose-response data. Stat J 6:40–57Google Scholar
  25. 25.
    Jackson D, White IR, Thompson SG (2010) Extending DerSimonian and Laird’s methodology to perform multivariate random effects meta-analyses. Stat Med 29:1282–1297PubMedCrossRefGoogle Scholar
  26. 26.
    Greenland S, Longnecker MP (1992) Methods for trend estimation from summarized dose-response data, with applications to meta-analysis. Am J Epidemiol 135:1301–1309PubMedGoogle Scholar
  27. 27.
    Riboli E, González CA, López-Abente G, Errezola M, Izarzugaza I, Escolar A, Nebot M, Hémon B, Agudo A (1991) Diet and bladder cancer in Spain: a multi-centre case–control study. Int J Cancer 49:214–219PubMedCrossRefGoogle Scholar
  28. 28.
    Negri E, La Vecchia C, Franceschi S, D’Avanzo B, Parazzini F (1991) Vegetable and fruit consumption and cancer risk. Int J Cancer 48:350–354PubMedCrossRefGoogle Scholar
  29. 29.
    Bruemmer B, White E, Vaughan TL, Cheney CL (1996) Nutrient intake in relation to bladder cancer among middle-aged men and women. Am J Epidemiol 144:485–495PubMedCrossRefGoogle Scholar
  30. 30.
    Yu Y, Hu J, Wang PP, Zou Y, Qi Y, Zhao P, Xe R (1997) Risk factors for bladder cancer: a case–control study in northeast China. Eur J Cancer Prev 6:363–369PubMedCrossRefGoogle Scholar
  31. 31.
    Pohlabeln H, Jöckel KH, Bolm-Audorff U (1999) Non-occupational risk factors for cancer of the lower urinary tract in Germany. Eur J Epidemiol 15:411–419PubMedCrossRefGoogle Scholar
  32. 32.
    Wakai K, Takashi M, Okamura K, Yuba H, Suzuki K, Murase T, Obata K, Itoh H, Kato T, Kobayashi M, Sakata T, Otani T, Ohshima S, Ohno Y (2000) Foods and nutrients in relation to bladder cancer risk: a case–control study in Aichi Prefecture, Central Japan. Nutr Cancer 38:13–22PubMedCrossRefGoogle Scholar
  33. 33.
    Peluso M, Airoldi L, Magagnotti C, Fiorini L, Munnia A, Hautefeuille A, Malaveille C, Vineis P (2000) White blood cell DNA adducts and fruit and vegetable consumption in bladder cancer. Carcinogenesis 21:183–187PubMedCrossRefGoogle Scholar
  34. 34.
    Pelucchi C, La Vecchia C, Negri E, Dal Maso L, Franceschi S (2002) Smoking and other risk factors for bladder cancer in women. Prev Med 35:114–120PubMedCrossRefGoogle Scholar
  35. 35.
    Wakai K, Hirose K, Takezaki T, Hamajima N, Ogura Y, Nakamura S, Hayashi N, Tajima K (2004) Foods and beverages in relation to urothelial cancer: case–control study in Japan. Int J Urol 11:11–19PubMedCrossRefGoogle 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 53:144–151PubMedCrossRefGoogle Scholar
  37. 37.
    Kellen E, Zeegers M, Paulussen A, Van Dongen M, Buntinx F (2006) Fruit consumption reduces the effect of smoking on bladder cancer risk. The Belgian case control study on bladder cancer. Int J Cancer 118:2572–2578PubMedCrossRefGoogle Scholar
  38. 38.
    García-Closas R, García-Closas M, Kogevinas M, Malats N, Silverman D, Serra C, Tardón A, Carrato A, Castaño-Vinyals G, Dosemeci M, Moore L, Rothman N, Sinha R (2007) Food, nutrient and heterocyclic amine intake and the risk of bladder cancer. Eur J Cancer 43:1731–1740PubMedCrossRefGoogle Scholar
  39. 39.
    Sacerdote C, Matullo G, Polidoro S, Gamberini S, Piazza A, Karagas MR, Rolle L, De Stefanis P, Casetta G, Morabito F, Vineis P, Guarrera S (2007) Intake of fruits and vegetables and polymorphisms in DNA repair genes in bladder cancer. Mutagenesis 22:281–285PubMedCrossRefGoogle Scholar
  40. 40.
    Tang L, Zirpoli GR, Guru K, Moysich KB, Zhang Y, Ambrosone CB, McCann SE (2008) Consumption of raw cruciferous vegetables is inversely associated with bladder cancer risk. Cancer Epidemiol Biomarkers Prev 17:938–944PubMedCrossRefGoogle Scholar
  41. 41.
    Lin J, Kamat A, Gu J, Chen M, Dinney CP, Forman MR, Wu X (2009) Dietary intake of vegetables and fruits and the modification effects of GSTM1 and NAT2 genotypes on bladder cancer risk. Cancer Epidemiol Biomarkers Prev 18:2090–2097PubMedCrossRefGoogle Scholar
  42. 42.
    Pavanello S, Mastrangelo G, Placidi D, Campagna M, Pulliero A, Carta A, Arici C, Porru S (2010) CYP1A2 polymorphisms, occupational and environmental exposures and risk of bladder cancer. Eur J Epidemiol 25:491–500PubMedCrossRefGoogle Scholar
  43. 43.
    Kellen E, Zeegers M, Buntinx F (2006) Selenium is inversely associated with bladder cancer risk: a report from the Belgian case–control study on bladder cancer. Int J Urol 13:1180–1184PubMedCrossRefGoogle Scholar
  44. 44.
    Steineck G, Norell SE, Feychting M (1988) Diet, tobacco and urothelial cancer. A 14-year follow-up of 16,477 subjects. Acta Oncol 27:323–327PubMedCrossRefGoogle Scholar
  45. 45.
    Shibata A, Paganini-Hill A, Ross RK, Henderson BE (1992) Intake of vegetables, fruits, beta-carotene, vitamin C and vitamin supplements and cancer incidence among the elderly: a prospective study. Br J Cancer 66:673–679PubMedCentralPubMedCrossRefGoogle Scholar
  46. 46.
    Chyou PH, Nomura AM, Stemmermann GN (1993) A prospective study of diet, smoking, and lower urinary tract cancer. Ann Epidemiol 3:211–216PubMedCrossRefGoogle Scholar
  47. 47.
    Michaud DS, Spiegelman D, Clinton SK, Rimm EB, Willett WC, Giovannucci EL (1999) Fruit and vegetable intake and incidence of bladder cancer in a male prospective cohort. J Natl Cancer Inst 91:605–613PubMedCrossRefGoogle Scholar
  48. 48.
    Zeegers MP, Goldbohm RA, van den Brandt PA (2001) Consumption of vegetables and fruits and urothelial cancer incidence: a prospective study. Cancer Epidemiol Biomarkers Prev 10:1121–1128PubMedGoogle Scholar
  49. 49.
    Michaud DS, Pietinen P, Taylor PR, Virtanen M, Virtamo J, Albanes D (2002) Intakes of fruits and vegetables, carotenoids and vitamins A, E, C in relation to the risk of bladder cancer in the ATBC cohort study. Br J Cancer 87:960–965PubMedCentralPubMedCrossRefGoogle Scholar
  50. 50.
    Larsson SC, Andersson SO, Johansson JE, Wolk A (2008) Fruit and vegetable consumption and risk of bladder cancer: a prospective cohort study. Cancer Epidemiol Biomarkers Prev 17:2519–2522PubMedCrossRefGoogle Scholar
  51. 51.
    Holick CN, De Vivo I, Feskanich D, Giovannucci E, Stampfer M, Michaud DS (2005) Intake of fruits and vegetables, carotenoids, folate, and vitamins A, C, E and risk of bladder cancer among women (United States). Cancer Causes Control 16:1135–1145PubMedCrossRefGoogle Scholar
  52. 52.
    Büchner FL, Bueno-de-Mesquita HB, Ros MM, Kampman E, Egevad L, Overvad K, Raaschou-Nielsen O, Tjønneland A, Roswall N, Clavel-Chapelon F, Boutron-Ruault MC, Touillaud M, Chang-Claude J, Kaaks R, Boeing H, Weikert S, Trichopoulou A, Lagiou P, Trichopoulos D, Palli D, Sieri S, Vineis P, Tumino R, Panico S, Vrieling A, Peeters PH, van Gils CH, Lund E, Gram IT, Engeset D, Martinez C, Gonzalez CA, Larrañaga N, Ardanaz E, Navarro C, Rodríguez L, Manjer J, Ehrnström RA, Hallmans G, Ljungberg B, Allen NE, Roddam AW, Bingham S, Khaw KT, Slimani N, Boffetta P, Jenab M, Mouw T, Michaud DS, Kiemeney LA, Riboli E (2009) Consumption of vegetables and fruit and the risk of bladder cancer in the European Prospective Investigation into Cancer and Nutrition. Int J Cancer 125:2643–2651PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Baodong Yao
    • 1
  • Yujie Yan
    • 1
  • Xianwu Ye
    • 2
  • Hong Fang
    • 1
  • Huilin Xu
    • 1
  • Yinan Liu
    • 1
  • Sheran Li
    • 2
  • Yanping Zhao
    • 1
  1. 1.Shanghai Minhang Center for Disease Control and PreventionShanghaiChina
  2. 2.The Fifth People’s Hospital of ShanghaiFudan UniversityShanghaiChina

Personalised recommendations