Critique 054. Role of alcohol intake and smoking on upper aerodigestive cancers – 6 September 2011

Anantharaman D, Marron M, Lagiou P, Samoli E, Ahrens W, Pohlabeln H, et al. Population attributable risk of tobacco and alcohol for upper aerodigestive tract cancer.  Oral Oncology 2011;47:725–731.

Authors’ Abstract

Tobacco and alcohol are major risk factors for upper aerodigestive tract (UADT) cancer and significant variation is observed in UADT cancer rates across Europe. We have estimated the proportion of UADT cancer burden explained by tobacco and alcohol and how this varies with the incidence rates across Europe, cancer sub-site, gender and age. This should help estimate the minimum residual burden of other risk factors to UADT cancer, including human papillomavirus.

We analysed 1981 UADT cancer cases and 1993 controls from the ARCAGE multi-centre study. We estimated the population attributable risk (PAR) of tobacco alone, alcohol alone and their joint effect. Tobacco and alcohol together explained 73% of UADT cancer burden of which nearly 29% was explained by smoking alone, less than 1% due to alcohol on its own and 44% by the joint effect of tobacco and alcohol. Tobacco and alcohol together explained a larger proportion of hypopharyngeal/laryngeal cancer (PAR = 85%) than oropharyngeal (PAR = 74%), esophageal (PAR = 67%) and oral cancer (PAR = 61%). Tobacco and alcohol together explain only about half of the total UADT cancer burden among women. Geographically, tobacco and alcohol explained a larger proportion of UADT cancer in central (PAR = 84%) than southern (PAR = 72%) and western Europe (PAR = 67%). While the majority of the UADT cancers in Europe are due to tobacco or the joint effect of tobacco and alcohol, our results support a significant role for other risk factors in particular, for oral and oropharyngeal cancers and also for UADT cancers in southern and western Europe.

Forum Comments

Background:  A recent case-control analysis from subjects living in areas of South America had results similar to those in the present study.1  That study showed that both alcohol consumption and smoking tended to increase the risk of such cancers, but the predominant cause was the combination of smoking and alcohol consumption.  The effects on risk were greater for smoking than for alcohol: for non-smokers, there was little effect of alcohol on risk.  An especially important finding in that study was that, among ex-drinkers and former smokers, the increased risks associated with alcohol and tobacco use decreased steadily as the time since quitting increased.  (A detailed critique of the earlier paper can be accessed at; under Recent Reviews, select Critique 049 from 1 August 2011.)

Comments on the present paper:  This was a case-control analysis, which is usual for uncommon types of cancer.  Controls were matched on age, gender, and area of residence, but some of the analyses also adjusted for educational level.  Forum members thought it unusual that the investigators considered as “ever drinkers” only subjects reporting 2 or more drinks per day; in most countries, the majority of light-to-moderate drinkers would be classified as never drinkers by this definition.  The data presented do not permit an evaluation of effects for lower levels of alcohol intake.  However, given that even at 2 or more drinks per day the effects of alcohol alone on population attributable risk were very small, it could be assumed that lighter drinking may have even less of a direct effect on the risk of these cancers.   

No information was available on diet (e.g., fruit and vegetable intake) or other lifestyle habits that may affect cancer risk.  Thus, it is not possible to judge whether subjects who were both smokers and drinkers may have had other unhealthy lifestyle habits as well.  Smoking and drinking might be just two visible markers of subjects with many unhealthy lifestyle habits.

Differences by type of beverage:  One Forum reviewer commented that differences on health between wine/beer consumers and those reporting spirits/liqueur suggest we should be careful speaking about “alcohol” in general.  The observation that “tobacco and alcohol explained a larger proportion of UADT cancer in central (PAR = 84%) than in southern (PAR = 72%) and western Europe (PAR = 67%) might be related to the type of alcoholic beverages more frequently consumed in different countries.  Data on women is Southern Europe go in the same direction.  The fact that among women, the PAR of tobacco was higher than that due to the joint effects of tobacco and alcohol in all geographic locations might be due to a protective role of the small quantities of alcohol (generally wine) usually consumed by women.

Reference from Forum review

1.  Szymańska K, Hung RJ, Wűnsch-Filho V, Eluf-Neto J, Curado MP, Koifman S, Matos E, Menezes A, Fernandez L, Daudt AW, Boffetta P, Brennan P.  Alcohol and tobacco, and the risk of cancers of the upper aerodigestive tract in Latin America: a case–control study.  Cancer Causes Control (2011) 22:1037–1046.  DOI 10.1007/s10552-011-9779-7

Forum Summary

This paper provies an extensive analysis of the proportion of the risk of upper aero-digestive tract (UADT) cancers in the population (the population attributable risk) may be due to alcohol consumption and/or smoking.  The analyses provide strong evidence that smoking is the most important factor in the risk of these cancers, and the risk is enhanced among those who also consume 2 or more drinks per day.  Alcohol alone (i.e., among non-smokers) has little effect on the risk. 

The authors state that their observations “are consistent with the hypothesis that alcohol acts as a carcinogen primarily because of its promoting effect on tobacco smoke.”  In terms of the population-attributable risk, the authors conclude that “Our findings confirm that tobacco and alcohol together explain 73% of total UADT cancer burden in Europe.”  Overall, tobacco use alone explained 28.7%, the combination of smoking and drinking 43.9%, and alcohol use alone only 0.4% of the population attributable risk.  Among women, the risk of these cancers was higher among smokers than among those who both smoked and consumed alcohol; this perhaps suggests that the moderate intake of wine, the most common beverage among European women, may play a role in reducing the risk associated with smoking. 

Forum reviewers thought that this was a very good paper, but hoped that in the future we would have more studies that evaluated the effects on risk of varying levels of alcohol consumption, differential effects of various beverages, and even differential effects according to subjects’ genetically determined differences in alcohol metabolizing enzymes.

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Comments on this paper were provided by the following members of the International Scientific Forum on Alcohol Research: 

Erik Skovenborg, MD, Scandinavian Medical Alcohol Board, Practitioner, Aarhus, Denmark

Harvey Finkel, MD, Hematology/Oncology, Boston University Medical Center, Boston, MA, USA

Giovanni de Gaetano, MD, PhD, Research Laboratories, Catholic University, Campobasso, Italy

R. Curtis Ellison, MD, Section of Preventive Medicine & Epidemiology, Boston University School of Medicine, Boston, MA, USA

Arne Svilaas, MD, PhD, general practice and lipidology, Oslo University Hospital, Oslo, Norway