The use of tobacco-free betel-quid in conjunction with alcohol/tobacco impacts early-onset age and carcinoma distribution for upper aerodigestive tract cancer

Abstract

Recognition of how risk factors affect the age when cancers are first diagnosed may help to establish more appropriate cancer screening and preventive strategies. To investigate the independent and synergistic 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. 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. Alcohol + Betel + Cigarette and Alcohol + Betel users exhibited 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 occurrence were correspondingly identified for these users aged 43, 49, 43, and 44 upward. 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.