© The Author 2007. Published by Oxford University Press.
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Alcohol Drinking in Never Users of Tobacco, Cigarette Smoking in Never Drinkers, and the Risk of Head and Neck Cancer: Pooled Analysis in the International Head and Neck Cancer Epidemiology Consortium
Affiliations of authors: International Agency for Research on Cancer, Lyon, France (MH, P. Brennan, SF, JB, P. Boffetta); INSERM, U794, Evry, France (SB); Institut Català d'Oncologia, Barcelona, Spain (XC); Fred Hutchinson Cancer Research Center, Seattle, WA (CC, SMS); Hospital Araujo Jorge, Goiania, Brazil (MPC); Aviano Cancer Centre, Aviano, Italy (LDM, RT); Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil (AWD); Specialized State Health Institute, Banská Bystrica, Slovakia (EF); Universidade de Sao Paulo, Sao Paulo, Brazil (VWF, JEN); National Cancer Institute, Bethesda, MD (RBH, DMW); Instituto de Investigación Epidemiológica, San José, Costa Rica (RH); Escola Nacional de Saude Publica, Rio de Janeiro, Brazil (SK); Istituto di Ricerche Farmacologiche Mario Negri and University of Milan, Milan, Italy (CLV); Penn State College of Medicine, Hershey, PA (PL, JM); Institut de médecine sociale et préventive [IUMSP], Université de Lausanne, Lausanne, Switzerland (FL); Institute of Public Health, Bucharest, Romania (DM); Institute of Oncology Angel H. Roffo, University of Buenos Aires, Argentina (EM); Universidade Federal de Pelotas, Pelotas, Brazil (AM); University of North Carolina School of Public Health, Chapel Hill, NC (AFO); National Institute of Environmental Health, Budapest, Hungary (PR); College of Public Health, University of Iowa, Iowa City, IA (ES); University of Texas M. D. Anderson Cancer Center, Houston, Texas (EMS, QW); Institute of Occupational Medicine, Lodz, Poland (NSD); Cancer Research Centre, Moscow, Russia (DZ); Maria Sklodowska Institute of Oncology, Warsaw, Poland (WZ); University of California, Los Angeles, School of Public Health, Los Angeles, CA (ZFZ)
Correspondence to: Mia Hashibe, PhD, Gene–Environment Epidemiology Group, International Agency for Research on Cancer, 150 cours Albert Thomas, 69008 Lyon, France (e-mail: hashibe{at}iarc.fr)
Background: At least 75% of head and neck cancers are attributable to a combination of cigarette smoking and alcohol drinking. A precise understanding of the independent association of each of these factors in the absence of the other with the risk of head and neck cancer is needed to elucidate mechanisms of head and neck carcinogenesis and to assess the efficacy of interventions aimed at controlling either risk factor.
Methods: We examined the extent to which head and neck cancer is associated with cigarette smoking among never drinkers and with alcohol drinking among never users of tobacco. We pooled individual-level data from 15 case–control studies that included 10244 head and neck cancer case subjects and 15227 control subjects, of whom 1072 case subjects and 5775 control subjects were never users of tobacco and 1598 case subjects and 4051 control subjects were never drinkers of alcohol. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models. All statistical tests were two-sided.
Results: Among never drinkers, cigarette smoking was associated with an increased risk of head and neck cancer (OR for ever versus never smoking = 2.13, 95% CI = 1.52 to 2.98), and there were clear dose–response relationships for the frequency, duration, and number of pack-years of cigarette smoking. Approximately 24% (95% CI = 16% to 31%) of head and neck cancer cases among nondrinkers in this study would have been prevented if these individuals had not smoked cigarettes. Among never users of tobacco, alcohol consumption was associated with an increased risk of head and neck cancer only when alcohol was consumed at high frequency (OR for three or more drinks per day versus never drinking = 2.04, 95% CI = 1.29 to 3.21). The association with high-frequency alcohol intake was limited to cancers of the oropharynx/hypopharynx and larynx.
Conclusions: Our results represent the most precise estimates available of the independent association of each of the two main risk factors of head and neck cancer, and they exemplify the strengths of large-scale consortia in cancer epidemiology.
| CONTEXT AND CAVEATS Prior knowledge Although at least 75% of head and neck cancers diagnosed in industrialized regions are attributable to the combination of cigarette smoking and alcohol drinking, the respective contributions of these risk factors to head and neck cancer risk are unclear because the two habits are strongly associated with each other. Study design A pooled analysis of data from 15 case–control studies of head and neck cancer risk and cigarette smoking among never drinkers and head and neck cancer risk and alcohol drinking among never users of tobacco. Contribution Among never drinkers, cigarette smoking was associated with an increased risk of head and neck cancer, and there were clear dose–response relationships for the frequency, duration, and number of pack-years of cigarette smoking. Among never users of tobacco, high-frequency alcohol consumption was associated with increased risks of cancers of the oropharynx/hypopharynx and larynx only. Implications Approximately one quarter of the head and neck cancers among the never drinkers were attributable to ever cigarette smoking, assuming a causal relationship. Only 7% of the head and neck cancers were attributable to alcohol drinking among the never users of tobacco, assuming a causal relationship. Limitations Misclassification of alcohol exposure, particularly exposure to hard liquors, and recall bias could have influenced the observed associations. Regional differences in social acceptance of tobacco habits and alcohol consumption may have influenced how a subject responded to questions about these practices in a face-to-face interview.
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Manuscript received November 21, 2006; revised February 23, 2007; accepted April 2, 2007.
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J Natl Cancer Inst 2007 99: 741.
J Natl Cancer Inst 2007 99: 741.
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