title: Environmental heavy metal as a potential risk factor for the progression of oral potentially malignant disorders in central Taiwan.
abstract: Oral cancer (OC) is a leading cause of death from cancer in men between the ages of 25 and 44 years in Taiwan. The overall 5-year survival rates for the four OC stages (I-IV) in Taiwan are approximately 70%, 30%, 20%, and 10%, respectively, indicating the importance of the early diagnosis of oral potentially malignant disorders (OPMDs). Previous studies indicated an association between the OC incidence and certain environmental heavy metal concentrations. If these associations do exist for OC, they may also be observed for OPMD. The purpose of this study is to explore the association between the development of OPMD to OC and environmental heavy metals. Oral submucous fibrosis (OSF) and oral leukoplakia (OL) are two major types of OPMD in Taiwan.
  
  
  
  A retrospective cohort study was conducted by Changhua Christian Hospital, the sole medical center in Changhua County, where 2725 male adult patients diagnosed with either OSF or OL between 2000 and 2014 were recruited. Data were analyzed by Cox regression and adjusted for smoking and betel-quid chewing.
  
  
  
  OPMD patients who resided in areas with high nickel concentrations (polluted levels) exhibited hazard ratios of 1.8-2 for OC relative to those who lived in areas with low nickel levels (P<0.01). Meanwhile, smokers with OPMDs had a hazard ratio of 2.8-2.9 relative to non-smokers. Betel-quid chewers had a 2.2-2.3 hazard ratio relative to non-chewers. Smoking, betel-quid chewing, and environmental nickel exposure are associated with an increased risk of OC development in OPMD patients. This study provides valuable findings on the environmental effects of heavy metals on human health. Enhanced surveillance of the condition of OPMD patients who have been exposed to high nickel concentrations may be crucial for OC prevention.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Changhua Christian Hospital, 135, Nan-Hsiao Street, Changhua 500, Taiwan.
authors.forename: Kuo-Yang
authors.initials: KY
authors.lastname: Tsai
authors.affiliation: Department of Internal Medicine, Changhua Christian Hospital, 135, Nan-Hsiao Street, Changhua 500, Taiwan; Graduate Institute of Statistics and Information Science, National Changhua University of Education, Changhua 500, Taiwan.
authors.forename: Che-Chun
authors.initials: CC
authors.lastname: Su
authors.affiliation: Green Energy and Environment Research Laboratories, Industrial Technology Research Institute, No. 195, Section 4, Chung Hsing Road, Chutung, Hsinchu 310, Taiwan.
authors.forename: Chi-Ting
authors.initials: CT
authors.lastname: Chiang
authors.affiliation: Graduate Institute of Statistics and Information Science, National Changhua University of Education, Changhua 500, Taiwan. Electronic address: d0022001@mail.ncue.edu.tw.
authors.forename: Yao-Ting
authors.initials: YT
authors.lastname: Tseng
authors.affiliation: Graduate Institute of Statistics and Information Science, National Changhua University of Education, Changhua 500, Taiwan. Electronic address: maiblian@cc.ncue.edu.tw.
authors.forename: Ie-Bin
authors.initials: IB
authors.lastname: Lian
mesh_terms: D000328:Adult; D018450:Disease Progression; D004781:Environmental Exposure / Q000009:adverse effects*; D004787:Environmental Pollution / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007972:Leukoplakia, Oral / Q000209:etiology* / Q000473:pathology; D008297:Male; D019216:Metals, Heavy / Q000009:adverse effects*; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000209:etiology* / Q000473:pathology; D009914:Oral Submucous Fibrosis / Q000209:etiology* / Q000473:pathology; D011230:Precancerous Conditions / Q000209:etiology* / Q000473:pathology; D012189:Retrospective Studies; D012307:Risk Factors; D013624:Taiwan
chemical_list: D019216:Metals, Heavy
keywords: Heavy metal; Mixture cure model; OPMD; Oral cancer