MOUNT SINAI JOURNAL OF MEDICINE 76:392–403, 2009 392 Risk of Upper Aerodigestive Tract Cancer Associated with Smoking with and without Concurrent Alcohol Consumption Alireza Ansary-Moghaddam, PhD, 1 Rachel R. Huxley, PhD, 1 Tai Hing Lam, PhD, 2 and Mark Woodward, PhD 3 1 George Institute for International Health, New South Wales, Australia 2 University of Hong Kong, Hong Kong, China 3 Mount Sinai School of Medicine, New York, NY ABSTRACT Background: Smoking and alcohol are major causal factors for upper aerodigestive tract cancer, but reliable quantification of the combined impact of smoking and alcohol on this cancer and its major subtypes has not been performed. Methods: A meta-analysis of studies that had published quantitative estimates of smoking and upper aerodigestive tract cancer by January 2007 was performed. Pooled estimates of relative risks were obtained. Publication bias was investigated through funnel plots and corrected if found to be present. Results: Overall, 85 studies with information on 53,940 individuals with upper aerodigestive tract cancer were included. The pooled estimate for the association between smoking and the risk of this cancer was 3.47 (95% confidence interval, 3.06–3.92). The risk remained elevated for a decade after smoking cessation but declined thereafter. Individuals who both smoked and consumed alcohol had double the risk of upper aerodigestive tract cancer in comparison with those who only smoked: the relative risk was 6.93 (95% confidence interval, Address Correspondence to: Mark Woodward Mount Sinai School of Medicine, New York, NY Email: mark.woodward@mssm.edu. 4.99–9.62) for the former and 2.56 (95% confidence interval, 2.20–2.97) for the latter (P < 0.001). Conclusions: Public health interventions that simul- taneously discourage smoking and heavy drinking would have greater benefits than would be expected from those that target only one of these risk fac- tors. Mt Sinai J Med 76:392–403, 2009.  2009 Mount Sinai School of Medicine Key Words: alcohol, cancer, meta-analysis, smoking, upper aerodigestive tract. Upper aerodigestive tract cancer (UADTC; oropharyngeal, esophageal, and laryngeal) is an important global problem, with nearly 1 million new cases occurring annually, three-quarters of which are in developing countries. 1 Accordingly, in developing countries, UADTC ranks among the 5 most common cancers in both men and women. 2,3 Additionally, the 5-year survival rates of some types of UADTC (eg, esophageal cancer) are among the lowest of all cancers at around 10%. 2,3 Cigarette smoking is a major causal factor for UADTC and its subtypes, 4 explaining approximately 40% of all UADTC cancer deaths globally. 5–7 Fur- thermore, alcohol consumption has been suggested to further exacerbate the effects of smoking on the risk of developing UADTC. 6 However, quantification of the additional risk among smokers conferred by alcohol on specific subtypes of UADTC has been hindered by studies that have had too few events to enable any reliable estimation. 6 Given the high and, in some regions, increasing prevalence of both smoking and alcohol consump- tion across large parts of the world, including devel- oping countries, 8–10 reliable quantification of the Published online in Wiley InterScience (www.interscience.wiley.com). DOI:10.1002/msj.20125  2009 Mount Sinai School of Medicine