Abstract

Background and AimsCoffee consumption and cigarette smoking are strongly associated, but whether this association is causal remains unclear. We sought to: (1) determine whether coffee consumption influences cigarette smoking causally, (2) estimate the magnitude of any association and (3) explore potential mechanisms.DesignWe used Mendelian randomization (MR) analyses of observational data, using publicly available summarized data from the Tobacco and Genetics (TAG) consortium, individual‐level data from the UK Biobank and in‐vitro experiments of candidate compounds.SettingThe TAG consortium includes data from studies in several countries. The UK Biobank includes data from men and women recruited across England, Wales and Scotland.ParticipantsThe TAG consortium provided data on n ≤ 38 181 participants. The UK Biobank provided data on 8072 participants.MeasurementsIn MR analyses, the exposure was coffee consumption (cups/day) and the outcome was heaviness of smoking (cigarettes/day). In our in‐vitro experiments we assessed the effect of caffeic acid, quercetin and p‐coumaric acid on the rate of nicotine metabolism in human liver microsomes and cDNA‐expressed human CYP2A6.FindingsTwo‐sample MR analyses of TAG consortium data indicated that heavier coffee consumption might lead to reduced heaviness of smoking [beta = −1.49, 95% confidence interval (CI) = −2.88 to −0.09]. However, in‐vitro experiments found that the compounds investigated are unlikely to inhibit significantly the rate of nicotine metabolism following coffee consumption. Further MR analyses in UK Biobank found no evidence of a causal relationship between coffee consumption and heaviness of smoking (beta = 0.20, 95% CI = –1.72 to 2.12).ConclusionsAmount of coffee consumption is unlikely to have a major causal impact upon amount of cigarette smoking. If it does influence smoking, this is not likely to operate via effects of caffeic acid, quercetin or p‐coumaric acid on nicotine metabolism. The observational association between coffee consumption and cigarette smoking may be due to smoking impacting on coffee consumption or confounding.

Highlights

  • Coffee consumption is associated with smoking [1,2,3]

  • Linkage disequilibrium (LD) pruning was performed: where pairs of variants were in linkage disequilibrium (LD), one of the variants was removed at random, ensuring total independence of all single nucleotide polymorphisms (SNPs) included in each model (r2 < 0.0006 in all instances)

  • Each additional cup of coffee consumed per day corresponded to a decrease in daily cigarette consumption of approximately 1.5 cigarettes per day within a fixed-effects framework

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Summary

Introduction

Observational studies show that coffee drinkers are more likely to be smokers than non-consumers [2,3] and smoke more heavily [1] This may arise via a number of possible mechanisms—constituents of coffee may have a pharmacological impact on the actions or metabolism of nicotine, or conditioning processes may lead to learned associations between the consumption of one and the other [1]. Findings Two-sample MR analyses of TAG consortium data indicated that heavier coffee consumption might lead to reduced heaviness of smoking [beta = À1.49, 95% confidence interval (CI) = À2.88 to À0.09]. Conclusions Amount of coffee consumption is unlikely to have a major causal impact upon amount of cigarette smoking If it does influence smoking, this is not likely to operate via effects of caffeic acid, quercetin or p-coumaric acid on nicotine metabolism. The observational association between coffee consumption and cigarette smoking may be due to smoking impacting on coffee consumption or confounding

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