The use of tobacco-free betel-quid in conjunction with alcohol / tobacco impacts early-onset age and carcinoma distribution for upper aerodigestive tract cancer Chien-Hung Lee 1,2 , Ka-Wo Lee 3 , Fu-Min Fang 4 , Deng-Chyang Wu 5 , Tien-Yu Shieh 6 , Hsiao-Ling Huang 6 , Chung-Ho Chen 7 , Ping-Ho Chen 7 , Mu-Kuan Chen 8 , Shou-Jen Kuo 9 , Cheng-Hsien Chang 10 , Yi-Shan Tsai 2 , Shang-Lun Chiang 2 , Hung-Pin Tu 11 , Bai-Hsiun Chen 12 , Ying-Chin Ko 2 1 Department of Public Health, Kaohsiung Medical University, Kaohsiung, Taiwan; 2 Center of Excellent for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 3 Department of Otolaryngology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 4 Department of Radiation Oncology, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan; 5 Department of Gastroenterology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 6 Department of Oral Hygiene, Kaohsiung Medical University, Kaohsiung, Taiwan; 7 School of Dentistry, Kaohsiung Medical University, Kaohsiung, Taiwan; 8 Oral Cancer Center, Changhua Christian Hospital, Changhua, Taiwan; 9 Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan; 10 Department of Ophthalmology, Kaohsiung Medical University, Kaohsiung, Taiwan; 11 Department of Public Health and Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 12 Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan BACKGROUND: Recognition of how risk factors affect the age when cancers are first diagnosed may help to establish more appropriate cancer screening and pre- ventive strategies. METHODS: To investigate the independent and syner- gistic effects of alcohol, tobacco-free betel-quid (TF-BQ), and cigarette use on diagnosis age and dissemination of upper aerodigestive tract squamous cell carcinoma (UADT-SCC), we recruited pathology-proven 1522 patients with UADT-SCC for study. RESULTS: A 49-, 53-, 57-, and 62-year-old stepwise older median age at carcinoma diagnosis was, respectively, found among patients with oral, pharyngeal, esophageal, and laryngeal cancer. Oral cavity (53.2%) and larynx (11.6%) were separately the dominant and recessive sites where the UADT-SCC occurred. Although alcohol and tobacco bestowed increased risks of earlier tumor occurrence only for oral / pharyngeal and oral cancers, respectively, TF-BQ was consistently observed to confer elevated age-associated risks for each UADT-SCC [adjusted hazard ratio (aHR) = 1.6–2.3]. Alcohol and TF-BQ joint consumers experienced a stepwise increased cumulative risk (CR) of contracting carcinomas of the larynx (46.2%), esophagus (47.5%), pharynx (53.5%), and oral cavity (60.5–71.0%), with >68% of CRs found among drinkers who started chewing before age 20. Alco- hol + Betel + Cigarette and Alcohol + Betel users exhibi- ted earlier diagnosis ages than non-users: 10 years ahead for oral cancer, 7, 17, and 12 years earlier for pharyngeal, esophageal, and laryngeal cancers. Noticeably, higher cumulative cancer risks regarding earlier tumor occur- rence were correspondingly identified for these users aged 43, 49, 43, and 44 upward. CONCLUSIONS: Tobacco-free betel-quid, in conjunction with alcohol and / or tobacco consumption, impacts early cancer occurrence for specific UADT-SCC and influences tumor site incidence pattern of these neoplasms. J Oral Pathol Med (2011) 40: 684–692 Keywords: age; alcohol; betel-quid; tobacco; upper aerodigestive cancer Abbreviations: ABC, alcohol, betel-quid, and cigarette; aHR, adjusted hazard ratio; CR, cumulative risk; SCC, squamous cell carcinoma; TF-BQ, tobacco-free betel-quid; UADT, upper aerodigestive tract Introduction The incidence of malignant neoplasms stemming from upper aerodigestive tract (UADT) containing tumors of the oral cavity, pharynx, larynx, and esophagus is increasing in both young and middled adults in Taiwan (1), that is, where alcohol, betel-quid, and cigarette (ABC) use is prevalent (2). Among men aged 25– 49 years, 27–32% of the new cancer cases were observed to occur at the four anatomical locations between the years 2000 and 2005, with oral cancer being the leading cause of all malignancies since 2003 (29.6–31.1 cases per Correspondence: Professor Ying-Chin Ko, MD, PhD, The Center of Excellence for Environmental Medicine, Kaohsiung Medical Univer- sity, No. 100 Shih-Chuan 1st Road, Kaohsiung 807, Taiwan. Tel: +886 7 311 4418, Fax: +886 7 316 2725, E-mail: ycko@kmu.edu.tw Accepted for publication January 11, 2011 J Oral Pathol Med (2011) 40: 684–692 ª 2011 John Wiley & Sons A/S Æ All rights reserved wileyonlinelibrary.com/journal/jop doi: 10.1111/j.1600-0714.2011.01022.x Journal of Oral Pathology & Medicine