title: The neoplastic impact of tobacco-free betel-quid on the histological type and the anatomical site of aerodigestive tract cancers.
abstract: Little is known about any consequences of swallowing tobacco-free betel-quid (TF-BQ) juice/remnants following chewing and its carcinogenic impact on the upper aerodigestive tract (UADT) to gastrointestinal tract (GIT). We investigated the neoplastic impact of TF-BQ on different anatomical locations along UADT and GIT, and differences according to their histological categories. We conducted a multicenter case-control study examining patients with 2,163 pathology-proven UADT and GIT cancers, comparing them with 2,250 control subjects. Generalized additive models, piecewise regression and polytomous logistic models were applied to identify possible dose-dependent structures and cancer risks. Contrary to nonsignificant GIT-adenocarcinoma risk (aOR=0.9), TF-BQ users experienced a 1.7- to 16.2-fold higher risk of UADT-squamous cell carcinomas than nonusers, with the peak risk discovered in oral neoplasms. We separately observed a curvilinear and linear TF-BQ dose-risk relationship in oral/pharyngeal/esophageal and laryngeal cancers. Chewers of betel inflorescence were generally at a greater UADT cancer risk. A higher first-piecewise increased risk of esophageal cancer was recognized among areca-fluid swallowers than among nonswallowers (continuous aOR=1.12 vs. 1.03). TF-BQ use accounted for 66.1-78.7% and 17.8-33.2% of the cases of oral/pharyngeal and esophageal/laryngeal cancers, respectively. However, a reduction from heavy TF-BQ consumption to low-to-moderate consumption only reduced 11.3-34.6% of etiologic fraction of oral/pharyngeal cancers. Alcohol supra-additively modified the risk of TF-BQ in determining the development of oral, pharyngeal and esophageal cancers. In conclusion, the interplay of TF-BQ and alcohol/tobacco use, combined with how chewing habit is practiced, influences carcinogenic consequences on anatomically diverse sites of UADT and GIT cancers, and histologically different types.
authors.affiliation: Department of Public Health, Kaohsiung Medical University, and Department of Otolaryngology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Chien-Hung
authors.initials: CH
authors.lastname: Lee
authors.forename: Ka-Wo
authors.initials: KW
authors.lastname: Lee
authors.forename: Fu-Min
authors.initials: FM
authors.lastname: Fang
authors.forename: Deng-Chyang
authors.initials: DC
authors.lastname: Wu
authors.forename: Shih-Meng
authors.initials: SM
authors.lastname: Tsai
authors.forename: Ping-Ho
authors.initials: PH
authors.lastname: Chen
authors.forename: Tien-Yu
authors.initials: TY
authors.lastname: Shieh
authors.forename: Chung-Ho
authors.initials: CH
authors.lastname: Chen
authors.forename: I-Chen
authors.initials: IC
authors.lastname: Wu
authors.forename: Hsiao-Ling
authors.initials: HL
authors.lastname: Huang
authors.forename: Bai-Hsiun
authors.initials: BH
authors.lastname: Chen
authors.forename: Cheng-Hsien
authors.initials: CH
authors.lastname: Chang
authors.forename: Mu-Kuan
authors.initials: MK
authors.lastname: Chen
authors.forename: Shah-Hwa
authors.initials: SH
authors.lastname: Chou
authors.forename: Yi-Shan
authors.initials: YS
authors.lastname: Tsai
authors.forename: Shang-Lun
authors.initials: SL
authors.lastname: Chiang
authors.forename: Ying-Chin
authors.initials: YC
authors.lastname: Ko
mesh_terms: D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects; D001114:Areca / Q000009:adverse effects*; D002273:Carcinogens / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000209:etiology / Q000473:pathology*; D016022:Case-Control Studies; D004938:Esophageal Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D005770:Gastrointestinal Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000473:pathology*; D006801:Humans; D015994:Incidence; D007822:Laryngeal Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010610:Pharyngeal Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000473:pathology*; D011379:Prognosis; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D013624:Taiwan / Q000453:epidemiology
chemical_list: D002273:Carcinogens