Critique 049: Effects of smoking and alcohol use on the risk of upper aero-digestive cancers – 1 August 2011
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
Background Cancers of the upper aerodigestive tract (UADT; including oral cavity, pharynx, larynx and oesophagus) have high incidence rates all over the world, and they are especially frequent in some parts of Latin America. However, the data on the role of the major risk factors in these areas are still limited.
Methods We have evaluated the role of alcohol and tobacco consumption, based on 2,252 upper aerodigestive squamous-cell carcinoma cases and 1,707 controls from seven centres in Brazil, Argentina, and Cuba.
Results We show that alcohol drinkers have a risk of UADT cancers that is up to five times higher than that of never-drinkers. A very strong effect of aperitifs and spirits as compared to other alcohol types was observed, with the ORs reaching 12.76 (CI 5.37–30.32) for oesophagus. Tobacco smokers were up to six times more likely to develop aerodigestive cancers than never-smokers, with the ORs reaching 11.14 (7.72–16.08) among current smokers for hypopharynx and larynx cancer. There was a trend for a decrease in risk after quitting alcohol drinking or tobacco smoking for all sites. The interactive effect of alcohol and tobacco was more than multiplicative. In this study, 65% of all UADT cases were attributable to a combined effect of alcohol and tobacco use.
Conclusions In this largest study on UADT cancer in Latin America, we have shown for the first time that a prevailing majority of UADT cancer cases is due to a combined effect of alcohol and tobacco use and could be prevented by quitting the use of either of these two agents.
Background Upper aero-digestive tract cancers (UADT), especially those of the oral cavity, pharynx, and larynx, are often referred to as alcohol-related cancers as it has been shown repeatedly that heavy drinkers, in particular, are at increased risk. The combination of heavy alcohol use and cigarette smoking is the key factor in increasing the risk of these cancers. While this paper only supports much previous research, it is from a part of the world (South America) from which little information on the topic is available, it focuses on groups of people where the occurrence of such cancers is high, and it is from a distinguished group of scientists from the International Agency for Research on Cancer (IRAC).
Comments on the paper: Of necessity, as these types of cancer are not common, most studies on them are based on case-control analyses rather than on prospective studies. In the present study, verification of the diagnosis was confirmed in all cases by pathologic reports. While the authors included cancer of the esophagus in their overall analyses, the findings for this cancer tended to differ from those for the other types of cancer. Forum reviewers were somewhat surprised at the authors’ mixing cigar smoking with cigarette smoking as a risk factor. From the carcinogenesis point of view, the burning temperature of cigars is significantly lower than that of cigarettes, and most cigar smokers do not inhale the smoke.
There was an extremely high response rate (95% for cases, 86% for controls). Chosen as controls were inpatients or outpatients from the same hospitals as the cases. Controls had diagnoses that were stated as “not related to tobacco or alcohol” (although the group included people with injuries, poisoning, and diseases of the circulatory system, which could relate to alcohol use). For ex-drinkers and former smokers, the investigators collected data on the time since the subjects quit such habits. Data on both current habits and cumulative alcohol and tobacco consumption were available. Analytic methods were appropriate.
Since tobacco smoke is more carcinogenic than alcohol, especially for beverages without any antioxidant properties, it is not surprising that refraining from smoking would have a bigger effect on risk than refraining from alcoholic drinks. No information was provided regarding the intake of fruits and vegetables, nor on the sources of saturated fat. These and other dietary factors may also affect the risk of these cancers.
Interaction of drinking and smoking: Overall, this study confirms that there is a tendency for an increase in risk for these cancers for both alcohol consumption and for tobacco use. More striking, however, was the strong interaction between these two exposures: heavy smokers and heavy drinkers were by far at the highest risk. For never-smokers, there was little effect of alcohol on the risk of these cancers, and none of the associations between alcohol and cancer among such subjects was statistically significant. As for the type of alcoholic beverage consumed, the risk for cancer was always highest among subjects stating that they consumed only aperitifs or spirits, with little apparent effect of the consumption of beer or wine.
For never-drinkers, the effects of increasing tobacco use remained significant for most categories, but the odds ratios for cancer risk were somewhat attenuated. However, the risk of hypo-pharyngeal/laryngeal cancer was markedly increased for smokers who had never consumed alcohol.
The large majority of subjects in both the case and control groups had used both alcohol and tobacco at some time in their lives. In comparison with never drinkers/never smokers, the odds ratios for oral/pharyngeal, hypo-pharyngeal/laryngeal, and esophageal cancers among subjects reporting both habits were 9.88, 13.17, and 6.07, respectively. The vast majority of cancers (about 85%) were attributed to the combination of alcohol and tobacco use.
Effects of quitting: An especially important finding in this 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. There were particularly strong reductions in risk after only a few years for subjects who stopped smoking. As stated by the authors, most of these cancers “could be prevented by quitting the use of either of these two agents.” Overall, the reductions from quitting were stronger for users of tobacco than for drinkers.
One Forum reviewer added: “In the near future it might be possible to identify genetic markers for specific cancers. This should add to the armamentarium of methods to prevent diseases by linking genetic susceptibility to environmental triggers. Smoking remains the main preventable cause of cancer in most countries of the world.” Being able to identify certain people who are at increased risk from genetic factors might help them to either not begin cigarette smoking, or help them to quit.
A case-control analysis from subjects living in areas of South America with high rates of upper aero-digestive tract cancers showed that both alcohol consumption and smoking tended to increase the risk of such cancers. However, the predominant cause of these cancers was the combination of smoking and alcohol consumption, with much higher risk than either exposure alone. The effects on risk were greater for smoking than for alcohol: for non-smokers, there was little effect of alcohol on risk. For non-drinkers, the risk of cancer associated with smoking was still increased, but was lower than it was for current drinkers.
An especially important finding in this 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. As stated by the authors, most of these cancers “could be prevented by quitting the use of either of these two agents.”
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Contributions to this critique by the International Scientific Forum on Alcohol Research were made by the following members:
David Van Velden, MD, Dept. of Pathology, Stellenbosch University, Stellenbosch, South Africa.
Gordon Troup, MSc, DSc, School of Physics, Monash University, Victoria, Australia.
Arne Svilaas, MD, PhD, general practice and lipidology, Oslo University Hospital, Oslo, Norway.
Erik Skovenborg, MD, Scandinavian Medical Alcohol Board, Practitioner, Aarhus, Denmark.
Harvey Finkel, MD, Hematology/Oncology, Boston University Medical Center, Boston, MA, USA.
R. Curtis Ellison, MD, Section of Preventive Medicine & Epidemiology, Boston University School of Medicine, Boston, MA, USA.