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A Prospective Investigation of Coffee Drinking and Bladder Cancer Incidence in the United States

Loftfield, Erikkaa; Freedman, Neal D.a; Inoue-Choi, Makia; Graubard, Barry I.b; Sinha, Rashmia

doi: 10.1097/EDE.0000000000000676

Background: In 1991, coffee was classified as a group 2B carcinogen, possibly carcinogenic to humans, based on limited epidemiologic evidence of a positive association with bladder cancer. In 2016, the International Agency for Research on Cancer downgraded this classification due to lack of evidence from prospective studies particularly for never smokers.

Methods: Baseline coffee drinking was assessed with a food frequency questionnaire in the NIH-AARP prospective cohort study. Among 469,047 US adults, who were cancer free at baseline, 6,012 bladder cancer cases (5,088 men and 924 women) were identified during >6.3 million person-years of follow-up. Multivariable-adjusted Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI), with non-coffee drinkers as the reference group.

Results: Coffee drinking was positively associated with bladder cancer in models adjusted for age and sex (HR for ≥4 cups/d relative to coffee nondrinkers = 1.91, 95% CI = 1.70, 2.14; P trend < 0.0001). However, the association was substantially attenuated after adjustment for cigarette smoking and other potential confounders (HR for ≥4 cups/d relative to coffee nondrinkers = 1.18, 95% CI = 1.05, 1.33; P trend = 0.0007). Associations were further attenuated after additional adjustment for lifetime smoking patterns among the majority of the cohort with this available data (P trend = 0.16). There was no evidence of an association among never smokers (P trend = 0.84).

Conclusions: Positive associations between coffee drinking and bladder cancer among ever smokers but not never smokers suggest that residual confounding from imperfect measurement of smoking or unmeasured risk factors may be an explanation for our positive findings.

Supplemental Digital Content is available in the text.

From the aMetabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD; and bBiostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.

Submitted 29 August 2016; accepted 13 April 2017.

Supported by the Intramural Research Program of the National Institutes of Health (NIH), Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services.

The authors report no conflicts of interest.

An investigator can apply for access to the NIH-AARP Diet & Health Study data using the STaRs system: The computing code could be obtained from the corresponding author if access to the data was granted.

E.L. and R.S. had primary responsibility for the final content of this manuscript. Cancer incidence data from the Atlanta metropolitan area were collected by the Georgia Center for Cancer Statistics, Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA. Cancer incidence data from California were collected by the California Cancer Registry, California Department of Public Health’s Cancer Surveillance and Research Branch, Sacramento, CA. Cancer incidence data from the Detroit metropolitan area were collected by the Michigan Cancer Surveillance Program, Community Health Administration, Lansing, MI. The Florida cancer incidence data used in this report were collected by the Florida Cancer Data System (Miami, FL) under contract with the Florida Department of Health, Tallahassee, FL. The views expressed herein are solely those of the authors and do not necessarily reflect those of the FCDC or FDOH. Cancer incidence data from Louisiana were collected by the Louisiana Tumor Registry, Louisiana State University Health Sciences Center School of Public Health, New Orleans, LA. Cancer incidence data from New Jersey were collected by the New Jersey State Cancer Registry, The Rutgers Cancer Institute of New Jersey, New Brunswick, NJ. Cancer incidence data from North Carolina were collected by the North Carolina Central Cancer Registry, Raleigh, NC. Cancer incidence data from Pennsylvania were supplied by the Division of Health Statistics and Research, Pennsylvania Department of Health, Harrisburg, PA. The Pennsylvania Department of Health specifically disclaims responsibility for any analyses, interpretations or conclusions. Cancer incidence data from Arizona were collected by the Arizona Cancer Registry, Division of Public Health Services, Arizona Department of Health Services, Phoenix, AZ. Cancer incidence data from Texas were collected by the Texas Cancer Registry, Cancer Epidemiology and Surveillance Branch, Texas Department of State Health Services, Austin, TX. Cancer incidence data from Nevada were collected by the Nevada Central Cancer Registry, Division of Public and Behavioral Health, State of Nevada Department of Health and Human Services, Carson City, NV.

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Correspondence: Erikka Loftfield, Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Dr. 6E320, Bethesda, MD, 20892. E-mail:

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