The cancer of upper aerodigestive tract (UADT) is a common cancers in the world. However, its lifetime risk by consumption of alcohol, betel and cigarettes remain to be elucidated. This study aimed to estimate lifetime risk of distinct UADT cancers and assess their associations with alcohol, betel and cigarette consumption. Three cohorts of 25,611 men were enrolled in 1982-1992 in Taiwan. The history of alcohol, betel and cigarette consumption was enquired through questionnaire interview. Newly developed UADT cancers were ascertained through computerized linkage with national cancer registry profile. Lifetime (30-80 years old) risk and multivariate-adjusted hazard ratio (HR adj ) of distinct UADT cancers by alcohol, betel and cigarette consumption were estimated. A total of 269 pathologically confirmed cases of UADT cancers were newly-diagnosed during 472,096 person-years of follow-up. The lifetime risk of UADT cancer was 9.42 and 1.65% for betel chewers and nonchewers, 3.22 and 1.21% for cigarette smokers and nonsmokers and 4.77 and 1.85% for alcohol drinkers and nondrinkers. The HR adj (95% confidence interval) of developing UADT cancer was 3.36 (2.51-4.49), 2.02 (1.43-2.84), 1.90 (1.46-2.49), respectively, for the consumption of betel, cigarette and alcohol. Alcohol, betel and cigarette had different effect on cancers at various anatomical sites of UADT. The cancer risk from the mouth, pharynx, esophagus to larynx increased for alcohol and cigarette consumption, but decreased for betel consumption. Alcohol, betel and cigarette consumption are independent risk predictors for distinct UADT cancers.The cancers of upper aerodigestive tract (UADT) including the sites of oral cavity, pharynx, esophagus and larynx are common cancers among males in the world. Its incidence has declined recently in most countries including France, the United States and India.1,2 However, the annual age-adjusted cancer incidence rates for oral cavity, pharynx, larynx and esophagus in Taiwanese males were 11.86, 4.71, 3.50 and 6.59 per 100,000, respectively, in 1995; and steadily increased to 25.28, 12.67, 3.65 and 11.94 per 100,000, respectively, in 2009. 3 Cancers of UADT have become an important public health issue in Taiwan in past decades.Numerous epidemiological evidences have shown that tobacco smoking and alcohol drinking are major risk factors for the development of UADT cancers, 4-6 which may explain 73% of UADT cancers in Europe. 7 In addition, large geographic variation in the incidence of UADT subsite cancers was observed in the world. This suggests other risk factors may play an important role in the carcinogenesis of UADT cancer as well. Betel nut/quid chewing is a common habit in Southeast Asia, and betel quid chewing prevalence is increasing in recent decades in Taiwan. 8 There is different ingredient of betel quid in Taiwan and other countries. The betel quid in Taiwan is chewed without tobacco and often chewed with inflorescence of piper betel and lime, but most chewers have cigarette smoking habits. 9 In a meta-...