Association of Coffee Drinking With Mortality by Genetic Variation in Caffeine Metabolism: Findings From the UK Biobank
Loftfield E, Cornelis MC, Caporaso N, Yu K, Sinha R, Freedman N
JAMA internal medicine · 137 citations
How it was studied
- Design
- Cohort study (indexed by PubMed)
- Studied in
- People
- Main outcome
- Clinical events such as disease or death
Who paid for it
- Funding
- Independent funding
- Nonprofit
- Wellcome Trust
- Government
- National Institute for Health and Care Research
- Government
- Medical Research Council
- Government
- National Institute for Health Research (NIHR)
- Grants
- Medical Research Council (MC_PC_17228)
Based on 4 listed funder(s).
Publication
- Published
- 2018-07-02 · JAMA Intern Med · vol. 178 · issue 8 · p. 1086
- Publisher
- American Medical Association
- Cited
- 187 citations · more than 99% of similar papers · 13.3× the field average
- Impact
- Top 10% most cited in its field
- References
- 34 works
- Access
- Open access (hybrid journal) · OTHER-OA
- Research areas
- Coffee research and impacts · Carcinogens and Genotoxicity Assessment · Pharmacogenetics and Drug Metabolism
- Keywords
- Medicine, Caffeine, Biobank, Hazard ratio, Demography, Cohort, Prospective cohort study, Population, Environmental health, Internal medicine, Confidence interval, Bioinformatics, Biology
- MeSH
- humans, cardiovascular diseases, caffeine, nutrition surveys, cause of death, survival rate, risk factors, follow-up studies, prospective studies, drinking behavior, life style, polymorphism, genetic, coffee, adult, aged, middle aged, biological specimen banks, female, male, genetic variation, united kingdom
6 authors
From US
- Erikka Loftfield · correspondingNational Institutes of Health; National Cancer Institute
- Marilyn C. CornelisNorthwestern University
- Neil E. CaporasoNational Institutes of Health; National Cancer Institute
- Kai Fun YuNational Institutes of Health; National Cancer Institute
- Rashmi R. SinhaNational Institutes of Health; National Cancer Institute
- Neal D. FreedmanNational Institutes of Health; National Cancer Institute
Abstract
Importance
Prospective cohorts in North America, Europe, and Asia show consistent inverse associations between coffee drinking and mortality, including deaths from cardiovascular disease and some cancers. However, concerns about coffee, particularly among people with common genetic polymorphisms affecting caffeine metabolism and among those drinking more than 5 cups per day, remain.
Objective
To evaluate associations of coffee drinking with mortality by genetic caffeine metabolism score.
Design, setting, and participants
The UK Biobank is a population-based study that invited approximately 9.2 million individuals from across the United Kingdom to participate. We used baseline demographic, lifestyle, and genetic data form the UK Biobank cohort, with follow-up beginning in 2006 and ending in 2016, to estimate hazard ratios (HRs) for coffee intake and mortality, using multivariable-adjusted Cox proportional hazards models. We investigated potential effect modification by caffeine metabolism, defined by a genetic score of previously identified polymorphisms in AHR, CYP1A2, CYP2A6, and POR that have an effect on caffeine metabolism. Of the 502 641 participants who consented with baseline data, we included those who were not pregnant and had complete data on coffee intake and smoking status (n = 498 134).
Exposures
Total, ground, instant, and decaffeinated coffee intake.
Main outcomes and measures
All-cause and cause-specific mortality.
Results
The mean age of the participants was 57 years (range, 38-73 years); 271 019 (54%) were female, and 387 494 (78%) were coffee drinkers. Over 10 years of follow-up, 14 225 deaths occurred. Coffee drinking was inversely associated with all-cause mortality. Using non-coffee drinkers as the reference group, HRs for drinking less than 1, 1, 2 to 3, 4 to 5, 6 to 7, and 8 or more cups per day were 0.94 (95% CI, 0.88-1.01), 0.92 (95% CI, 0.87-0.97), 0.88 (95% CI, 0.84-0.93), 0.88 (95% CI, 0.83-0.93), 0.84 (95% CI, 0.77-0.92), and 0.86 (95% CI, 0.77-0.95), respectively. Similar associations were observed for instant, ground, and decaffeinated coffee, across common causes of death, and regardless of genetic caffeine metabolism score. For example, the HRs for 6 or more cups per day ranged from 0.70 (95% CI, 0.53-0.94) to 0.92 (95% CI, 0.78-1.10), with no evidence of effect modification across strata of caffeine metabolism score (P = .17 for heterogeneity).
Conclusions and relevance
Coffee drinking was inversely associated with mortality, including among those drinking 8 or more cups per day and those with genetic polymorphisms indicating slower or faster caffeine metabolism. These findings suggest the importance of noncaffeine constituents in the coffee-mortality association and provide further reassurance that coffee drinking can be a part of a healthy diet.
Abstract via Europe PMC. Copyright remains with the authors or publisher.
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