The neoplastic impact of tobacco-free betel-quid on the histological type and the anatomical site of aerodigestive tract cancers

• Published in: International journal of cancer 2012-09, Vol.131 (5), p.E733-E743
• Main Authors: Lee, Chien-Hung, Lee, Ka-Wo, Fang, Fu-Min, Wu, Deng-Chyang, Tsai, Shih-Meng, Chen, Ping-Ho, Shieh, Tien-Yu, Chen, Chung-Ho, Wu, I-Chen, Huang, Hsiao-Ling, Chen, Bai-Hsiun, Chang, Cheng-Hsien, Chen, Mu-Kuan, Chou, Shah-Hwa, Tsai, Yi-Shan, Chiang, Shang-Lun, Ko, Ying-Chin
• Format: Article
• Language: English
• Subjects: Adult; Aged; alcohol drinking; Alcohol Drinking - adverse effects; anatomical site; Areca - adverse effects; areca nut; Cancer; Carcinogens - pharmacology; Carcinoma, Squamous Cell - epidemiology; Carcinoma, Squamous Cell - etiology; Carcinoma, Squamous Cell - pathology; Case-Control Studies; Esophageal Neoplasms - epidemiology; Esophageal Neoplasms - etiology; Esophageal Neoplasms - pathology; Female; Follow-Up Studies; Gastric cancer; gastrointestinal cancer; Gastrointestinal Neoplasms - epidemiology; Gastrointestinal Neoplasms - etiology; Gastrointestinal Neoplasms - pathology; Histology; Humans; Incidence; Laryngeal Neoplasms - epidemiology; Laryngeal Neoplasms - etiology; Laryngeal Neoplasms - pathology; Male; Medical research; Middle Aged; Pharyngeal Neoplasms - epidemiology; Pharyngeal Neoplasms - etiology; Pharyngeal Neoplasms - pathology; Prognosis; Risk Factors; Smoking - adverse effects; Taiwan - epidemiology; Tobacco; tobacco smoking; upper aerodigestive cancer
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.27401

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.