Does coffee consumption impact on heaviness of smoking?

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.

Investigating causal associations between use of nicotine, alcohol, caffeine and cannabis: a two‐sample bidirectional Mendelian randomization study

“…In the other direction, a recent comprehensive three‐part study reported some evidence for a causal, negative effect of caffeine use on CPD with a two‐sample MR method on summary‐level data, but not with MR on individual‐level data or in‐vitro experiments . With a slightly different genetic instrument, we also found mainly negative effect sizes of caffeine use on CPD, but these were not significant.…”

Mendelian Randomization Studies of Coffee and Caffeine Consumption

“…When individual-level data are available, a common strategy is to restrict SNP-outcome analysis to coffee drinkers arguing that the SNPs are associated with coffee drinking (heaviness) and thus causal relationships should only be observed among coffee drinkers (a form of gene-environment interaction) [ 43 , 44 , 48 , 49 , 56 , 59 , 66 ]. SNP-outcome associations among non-drinkers (‘negative control sample’) would suggest a violation in at least one of the assumptions [ 59 , 66 ].…”

“…Potential mechanisms include shared genetic and/or shared environmental factors (i.e., common liability) or a causal influence of one on the other [ 71 ]. The co-occurrence of coffee/caffeine use with other substance use behaviors has been investigated in four MR studies [ 46 , 48 , 49 , 51 ]. Three of these studies employed bidirectional MR [ 46 , 49 , 51 ], in which IVs for each substance use were used to evaluate causal effects and their direction [ 23 , 72 ].…”

“…The results suggested shared genetic factors for caffeine/coffee intake and smoking behavior, rather than a causal influence of one behavior on the other. Ware and colleagues [ 48 ] specifically focused on the causal role of coffee consumption on smoking heaviness. Two-sample MR analyses indicated that heavier coffee consumption might lead to reduced heaviness of smoking.…”

“…Single studies investigated and provided support for a causal role of coffee in reducing risk of gout [ 14 ] and increasing risk of osteoarthritis [ 57 ]. Four studies examined the co-occurrence of caffeine use and other substances with conflicting results [ 46 , 48 , 49 , 51 ]. For the remaining outcomes, studies did not provide clear support for a causal role of coffee or caffeine, but often acknowledged limitations (such as low statistical power, pleiotropy and collider bias), such that a causal role cannot yet be ruled out.…”