Coffee consumption and risk of bladder cancer: a pooled analysis of 501,604 participants from 12 cohort studies in the BLadder Cancer Epidemiology and Nutritional Determinants (BLEND) international study

  • Evan Y. W. Yu
  • Yanan Dai
  • Anke WesseliusEmail author
  • Frits van Osch
  • Maree Brinkman
  • Piet van den Brandt
  • Eric J. Grant
  • Emily White
  • Elisabete Weiderpass
  • Marc Gunter
  • Bertrand Hemon
  • Maurice P. Zeegers


Recent epidemiological studies have shown varying associations between coffee consumption and bladder cancer (BC). This research aims to elucidate the association between coffee consumption and BC risk by bringing together worldwide cohort studies on this topic. Coffee consumption in relation to BC risk was examined by pooling individual data from 12 cohort studies, comprising of 2601 cases out of 501,604 participants. Pooled multivariate hazard ratios (HRs), with corresponding 95% confidence intervals (CIs), were obtained using multilevel Weibull regression models. Furthermore, dose–response relationships were examined using generalized least squares regression models. The association between coffee consumption and BC risk showed interaction with sex (P-interaction < 0.001) and smoking (P-interaction = 0.001). Therefore, analyses were stratified by sex and smoking. After adjustment for potential confounders, an increased BC risk was shown for high (> 500 ml/day, equivalent to > 4 cups/day) coffee consumption compared to never consumers among male smokers (current smokers: HR = 1.75, 95% CI 1.27–2.42, P-trend = 0.002; former smokers: HR = 1.44, 95% CI 1.12–1.85, P-trend = 0.001). In addition, dose–response analyses, in male smokers also showed an increased BC risk for coffee consumption of more than 500 ml/day (4 cups/day), with the risk of one cup (125 ml) increment as 1.07 (95% CI 1.06–1.08). This research suggests that positive associations between coffee consumption and BC among male smokers but not never smokers and females. The inconsistent results between sexes and the absence of an association in never smokers indicate that the associations found among male smokers is unlikely to be causal and is possibly caused by residual confounding of smoking.


Bladder cancer Coffee consumption Smoking Dose–response analyses Cohort study 



BLadder Cancer Epidemiology and Nutritional Determinants


Bladder cancer


Generalized least squares


International Agency for Research on Cancer


European Prospective Investigation into Cancer and Nutrition Cohort Studies


NetherLands Cohort Study


VITamins And Lifestyle cohort study


Radiation Effects Research Foundation-Life Span Study


Food frequency questionnaires


International classification of diseases for oncology


Non-muscle invasive bladder cancer


Muscle invasive bladder cancer


Hazard ratio


Confidence interval


Cytochrome P450 1A2


Polycyclic aromatic hydrocarbons


Ataxia-telangiectasia mutated


Body Mass Index


Socioeconomic status











We gratefully acknowledge all principal investigators for their willingness to participate in this jointed project. The author E Y.W. Yu gives thanks to the financial support from China Scholarship Council (No. 201706310135).

Author contributions

Study conception and design: AW and MPZ; Analyses and interpretation of data: EYY and YD; Drafting of the manuscript: EYY and YD; Revised the manuscript: AW, FVO, MB and MPZ; Provided the data: PvdB, EG, EW, EW, MG, BH; Approved the manuscript: all authors.


This work was partly funded by the World Cancer Research Fund International (WCRF 2012/590) and European Commission (FP7-PEOPLE-618308). The NetherLands Cohort Study on diet and cancer was supported by the Dutch Cancer Society. The RERF atomic bomb survivors Study was supported by The Radiation Effects Research Foundation (RERF), Hiroshima and Nagasaki, Japan, a public interest foundation funded by the Japanese Ministry of Health, Labour and Welfare (MHLW) and the US Department of Energy (DOE). The research was also funded in part through DOE award DE-HS0000031 to the National Academy of Sciences. This publication was supported by RERF Research Protocol RP-A5-12. The VITamins and Lifestyle Study (VITAL) was supported by a Grant (R01CA74846) from the National Cancer Institute. The European Prospective Investigation into Cancer and Nutrition (EPIC) was carried out with financial support of the ‘Europe Against Cancer’ Programme of the European Commission (SANCO); Ligue contre le Cancer (France); Société 3 M (France); Mutuelle Générale de l’Éducation Nationale; Institut National de la Santé et de la Recherche Médicale (INSERM); Institute Gustave Roussy; German Cancer Aid; German Cancer Research Centre; German Federal Ministry of Education and Research; Health Research Fund (FIS) of the Spanish Ministry of Health; the Spanish Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra; Cancer Research UK; Medical Research Council, UK; Stroke Association, UK; British Heart Foundation; Department of Health, UK; Food Standards Agency, UK; Wellcome Trust, UK; Greek Ministry of Health; Greek Ministry of Education; Italian Association for Research on Cancer; Italian National Research Council; Dutch Ministry of Public Health, Welfare and Sports; Dutch Prevention Funds; LK Research Funds; Dutch ZON (Zorg Onderzoek Nederland); World Cancer Research Fund; Swedish Cancer Society; Swedish Scientific Council; Regional Government of Skane, Sweden; Norwegian Cancer Society; Norwegian Research Council. Partial support for the publication of this supplement was provided by the Centre de Recherche et d’Information Nutritionnelles (CERIN).

Compliance with ethical standards

Conflict of interest

All the authors declare no conflict of interest.

Ethics approval and consent to participate

Each participating study has been approved by the local ethic committee. Informed consent was obtained from all individual participants included in each study.

Supplementary material

10654_2019_597_MOESM1_ESM.docx (375 kb)
Supplementary material 1 (DOCX 375 kb)


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Copyright information

© Springer Nature B.V. 2020

Authors and Affiliations

  • Evan Y. W. Yu
    • 1
  • Yanan Dai
    • 1
  • Anke Wesselius
    • 1
    Email author
  • Frits van Osch
    • 1
  • Maree Brinkman
    • 1
    • 2
    • 3
  • Piet van den Brandt
    • 4
  • Eric J. Grant
    • 5
  • Emily White
    • 6
  • Elisabete Weiderpass
    • 7
  • Marc Gunter
    • 7
  • Bertrand Hemon
    • 7
  • Maurice P. Zeegers
    • 1
    • 8
    • 9
  1. 1.Department of Complex Genetics and Epidemiology, School of Nutrition and Translational Research in MetabolismMaastricht UniversityMaastrichtThe Netherlands
  2. 2.Department of Clinical Studies and Nutritional EpidemiologyNutrition Biomed Research InstituteMelbourneAustralia
  3. 3.Cancer Epidemiology DivisionCancer Council VictoriaMelbourneAustralia
  4. 4.Department of Epidemiology, Schools for Oncology and Developmental Biology and Public Health and Primary CareMaastricht University Medical CentreMaastrichtThe Netherlands
  5. 5.Department of EpidemiologyRadiation Effects Research FoundationHiroshimaJapan
  6. 6.Fred Hutchinson Cancer Research CenterSeattleUSA
  7. 7.International Agency for Research on Cancer World Health OrganizationLyonFrance
  8. 8.CAPHRI School for Public Health and Primary CareMaastricht UniversityMaastrichtThe Netherlands
  9. 9.School of Cancer SciencesUniversity of BirminghamBirminghamUK

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