Pipe smoking and cancers of the upper digestive tract Giorgia Randi 1,2 * , Lorenza Scotti 1 , Cristina Bosetti 1 , Renato Talamini 3 , Eva Negri 1 , Fabio Levi 4 , Silvia Franceschi 5 and Carlo La Vecchia 1,2 1 Department of Epidemiology, Istituto di Ricerche Farmacologiche ‘‘Mario Negri’’, Milan, Italy 2 Istituto di Statistica Medica e Biometria ‘‘G.A. Maccacaro’’, Universita` degli Studi di Milano, Milan, Italy 3 Servizio di Epidemiologia e Biostatistica, Centro di Riferimento Oncologico, Aviano, Italy 4 Unit  e d’ epid emiologie du cancer, Institut Universitaire de M edicine Sociale et Pr eventive, Universite´ de Lausanne, Lausanne, Switzerland 5 International Agency for Research on Cancer, Lyon, France Pipe smoking has been related to the risk of cancers of the upper digestive and respiratory tract, but quantification of the risk for exclusive pipe smokers is still limited. To analyse the association between exclusive pipe smoking and cancers of the upper digestive tract, we used data from a series of case–control studies conducted in Italy and Switzerland between 1984 and 1999. After excluding cigarette and cigar smokers, 41 male oral and pharyngeal cancer cases, 52 male oesophageal cancer cases and 1,032 male controls were included in the present analysis. Odds ratios (OR) of cancers were estimated by the mean of unconditional multivariate logistic regression, including terms for age, study centre, education, body mass index, and alcohol drinking. Compared to never smokers, exclusive pipe smokers had an OR of 8.7 [95% confidence inter- vals (CI): 4.0–18.9] of all upper digestive tract cancers. The OR was 12.6 for oral and pharyngeal and 7.2 for oesophageal cancer. Pipe smokers who were also heavy alcohol drinkers had an OR of 38.8 (95% CI: 13.6–110.9) as compared to never smokers and light drinkers. Thus, pipe smoking and heavy alcohol drinking appears to interact at least on a multiplicative model. ' 2007 Wiley-Liss, Inc. Key words: digestive cancer; pipe smoking; case–control study; risk factors Pipe smoking has been related to the risk of cancers of the upper digestive and respiratory tracts, 1,2 but quantification of the risk for exclusive pipe smokers is still limited. The American Cancer Soci- ety Cancer Prevention Study II (ACS-CPS II) 2 reported relative risk (RR) of oral and pharyngeal cancers of 3.9, based on 15 deaths, and of oesophageal cancer of 2.4, based on 20 deaths, for current pipe smokers. Another cohort of 25,129 Swedish men en- rolled in 1963 and followed-up to 1979 gave RRs of 1.4 for cancers of the oral cavity, pharynx and larynx (based on 3 deaths) and of 3.6 for cancer of the oesophagus (based on 6 deaths). 3 Other cohort studies from the USA 4,5 reported similar RR for oral, pharyngeal and oesophageal cancers, again based on small num- bers. Finally, in a study including 104 case/control pairs from Bei- jing, China, the multivariate odds ratio (OR) of oral cancer among exclusive pipe smoking was 5.7 in males and 4.9 in females. 6 To provide further quantification of the risk of upper digestive tract neoplasms for exclusive pipe smokers, we analysed data from a network of case–control studies conducted in Italy and Switzerland. Material and methods The present analysis is based on data from 3 hospital-based case–control studies of cancers of the oral cavity and pharynx, and 3 case–control studies of the cancer of the oesophagus, whose methods have already been described. 7–11 Only male subjects were included in the present analysis, since female cancers of the upper digestive tract are rare, and the proportion of female pipe smokers is negligible. Two Italian case–control studies on oral and pharyngeal cancers were conducted between 1984 and 1997 in the greater Milan area and the provinces of Pordenone, Rome, and Latina on 961 inci- dent, histologically confirmed male cases. 7,8 Another study on oral and pharyngeal cancers was conducted between 1992 and 1997 in the Swiss Canton of Vaud and included 126 male cases. 10 Two Italian studies on oesophageal cancer were conducted between 1984 and 1998 in the greater Milan area and in the prov- inces of Pordenone and Padua on 618 male cases. 9 Another study on oesophageal cancer was conducted between 1992 and 1999 in the Canton of Vaud on 82 cases. 11 Thus, 1,787 male cases (1,087 cases of oral and pharyngeal cancers and 700 of oesophageal can- cer) aged between 25 and 82 years (median age 59 years) were included in the original studies. In all case–control studies, con- trols were men admitted to the same network of hospitals as cases for a wide spectrum of acute, non-neoplastic conditions, neither related to smoking and alcohol consumption nor to long-term diet modifications. Overall, there were 3,829 nonoverlapping controls aged between 25 and 85 years (median age 57 years). Of these 27% were admitted for non-alcohol-related traumas, 28% for nontrau- matic orthopaedic disorders, 28% for acute surgical conditions, and 17% for miscellaneous other illnesses, including eye, ear, nose, throat, skin or dental disorders. To analyze the association between pipe smoking and cancers of upper digestive tract we considered data on exclusive pipe smokers and never smokers, excluding cigarette and/or cigar smokers. Thus, the present analyses are based on 41 cases (median age 60 years) of oral and pharyngeal cancers, 52 cases (median age 62 years) of oesophageal cancer, and 1,032 controls (median age 56 years). Response rate was over 95% in Italy, and around 85% in Swit- zerland for both cases and controls. Trained interviewers inter- viewed cases and controls during their hospital stay using similar structured questionnaires. These included information on socio- demographic characteristics, anthropometric measures, lifestyle habits, such as tobacco smoking and alcohol drinking, a problem- oriented personal medical history, and family history of cancer. The section on smoking included question on smoking status (never, current, former smokers), daily number of cigarettes or cigars and grams of tobacco for pipe smoked, age at starting, dura- tion of the habit and, for former smokers, age at smoking cessa- tion. Former smokers were subjects who had abstained from any type of smoking for at least 12 months. ORs and the corresponding 95% confidence intervals (CIs) were derived from unconditional multivariate logistic regression models, fitted by the method of maximum likelihood, 12 including terms for age (quinquennia), study centre, years of education (<7, Grant sponsors: Italian Association for Cancer Research, Italian and Swiss Leagues Against Cancer; Grant sponsor: Swiss Foundation for Research Against Cancer; Grant numbers: AKT 413 and 700; Grant spon- sor: Italian Ministry of Research; Grant number: PRIN 2005. *Correspondence to: Istituto di Ricerche Farmacologiche ‘‘Mario Negri’’-Via Eritrea, 62-20157 Milano, Italy. Fax: 10039-02-33200231. E-mail: randi@marionegri.it Received 22 December 2006; Accepted after revision 14 March 2007 DOI 10.1002/ijc.22791 Published online 13 July 2007 in Wiley InterScience (www.interscience. wiley.com). Int. J. Cancer: 121, 2049–2051 (2007) ' 2007 Wiley-Liss, Inc. Publication of the International Union Against Cancer