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

Abstract

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, 6012 bladder cancer cases (5088 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 (hazard ratio [HR] for ≥4 cups/day 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/day 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.

Association between coffee consumption and risk of bladder cancer in a meta-analysis of 16 prospective studies

“…For studies of coffee consumption and smoking-related cancers including bladder cancer, potential confounding by smoking merits particular attention. Observationally [5, 6] and genetically [32], heavier coffee consumers are more likely to be smokers. In a large cohort of US population [6], only 5.3% of coffee non-drinkers were current smokers, whereas the corresponding data in those consuming ≥4 cups/d of coffee was 25.8%.…”

“…Observationally [5, 6] and genetically [32], heavier coffee consumers are more likely to be smokers. In a large cohort of US population [6], only 5.3% of coffee non-drinkers were current smokers, whereas the corresponding data in those consuming ≥4 cups/d of coffee was 25.8%. For current smokers, coffee consumption tends to be associated with larger smoking amount [6] and longer smoking duration [31]; for former smokers, habitual coffee drinkers are likely to have been quitting smoking for shorter duration [6].…”

“…In a large cohort of US population [6], only 5.3% of coffee non-drinkers were current smokers, whereas the corresponding data in those consuming ≥4 cups/d of coffee was 25.8%. For current smokers, coffee consumption tends to be associated with larger smoking amount [6] and longer smoking duration [31]; for former smokers, habitual coffee drinkers are likely to have been quitting smoking for shorter duration [6]. All these coffee-related smoking features are associated with increased risk of bladder cancer when comparing with never smoking [33].…”

Mutational Landscape and Environmental Effects in Bladder Cancer

“…Current evidence remains equivocal whether coffee consumption may be associated with risk of bladder cancer. Some analyses showed positive association [ 82 , 83 , 84 ], while other analyses demonstrated inverse association [ 85 , 86 ]. Some reports concluded that no statistically significant association was observed [ 13 , 87 ].…”

Prevention of bladder cancer incidence and recurrence

“…In the past, coffee has been regarded as a potential carcinogen because of a reported association between increased coffee intake and higher bladder cancer risk. However, several new studies including a recent case-control study revealed that residual confounding factors, especially smoking status which is correlated with coffee consumption, may have been responsible for this association [8,9]. Indeed, a pooled analysis of two Japanese cohort studies reported a protective effect of increased coffee consumption [10].…”