title: Fine Particle Pollution, Alanine Transaminase, and Liver Cancer: A Taiwanese Prospective Cohort Study (REVEAL-HBV).
abstract: BACKGROUND
  Exposure to fine particulate matter (PM2.5) may promote hepatic tumorgenesis through low-grade inflammation. Therefore, we assessed the association of long-term exposure levels of PM2.5 and subsequent risk of hepatocellular carcinoma (HCC) and investigated the mediation effect of inflammation as represented by alanine aminotransferase (ALT) on this association.
  
  
  METHODS
  Between 1991 and 1992, we recruited 23 820 participants in Taiwan with no history of HCC. Case patients of HCC were ascertained through computerized data linkage with the National Cancer Registry and death certification systems. Participants' exposures to PM2.5 were based on a four-year average retrieved from stationary monitoring sites. Cox proportional hazards models were used to assess the association between PM2.5 exposure and HCC incidence. Mediation effects of ALT on PM2.5-associated HCC incidence were estimated.
  
  
  RESULTS
  A total of 464 HCC cases were newly diagnosed with a median follow-up of 16.9 years. Statistically significantly increasing trends between PM2.5 exposures and ALT were observed on the Main Island and Penghu Islets. The adjusted hazard ratio (HR) for HCC on the Penghu Islets was 1.22 (95% confidence interval [CI] = 1.02 to 1.47) per PM2.5 interquartile range (IQR) increment (0.73 µg/m(3)) exposure. We also found a positive association between PM2.5 exposure (per IQR increment, 13.1 µg/m(3)) and HCC incidence on the Main Island. Furthermore, ALT had a statistically significant mediation effect on PM2.5-associated HCC incidence (HR = 1.17, 95% CI = 1.02 to1.52 on the Main Island; HR = 1.04, 95% CI = 1.03 to 1.07 on the Penghu Islets) per PM2.5 IQR increment.
  
  
  CONCLUSIONS
  Long-term PM2.5 exposure increased the risk for liver cancer, and chronic inflammation of the liver may underlie the pathogenesis.
authors.affiliation: Affiliations of authors: Department of Environmental and Occupational Health, National Cheng Kung University , Tainan , Taiwan (WCP, MJC, HJS); Department of Epidemiology (WCP, YTH) and Department of Biostatistics (YTH), Brown University , Providence, RI ; Institute of Environmental and Occupational Health Sciences (WCP) and Institute of Clinical Medicine (HIY), National Yang-Ming University , Taipei , Taiwan ; Department of Forestry and Natural Resources, National Chiayi University , Chiayi , Taiwan (CDW); Department of Environmental Health, Harvard School of Public Health , Boston, MA (CDW); National Environmental Health Research Center, National Health Research Institutes , Miaoli , Taiwan (MJC); Genomics Research Center, Academia Sinica , Taipei , Taiwan (CJC, HIY); Graduate Institute of Epidemiology and Preventive Medicine, National Taiwan University , Taipei , Taiwan (CJC).
authors.forename: Wen-Chi
authors.initials: WC
authors.lastname: Pan
authors.affiliation: Affiliations of authors: Department of Environmental and Occupational Health, National Cheng Kung University , Tainan , Taiwan (WCP, MJC, HJS); Department of Epidemiology (WCP, YTH) and Department of Biostatistics (YTH), Brown University , Providence, RI ; Institute of Environmental and Occupational Health Sciences (WCP) and Institute of Clinical Medicine (HIY), National Yang-Ming University , Taipei , Taiwan ; Department of Forestry and Natural Resources, National Chiayi University , Chiayi , Taiwan (CDW); Department of Environmental Health, Harvard School of Public Health , Boston, MA (CDW); National Environmental Health Research Center, National Health Research Institutes , Miaoli , Taiwan (MJC); Genomics Research Center, Academia Sinica , Taipei , Taiwan (CJC, HIY); Graduate Institute of Epidemiology and Preventive Medicine, National Taiwan University , Taipei , Taiwan (CJC).
authors.forename: Chih-Da
authors.initials: CD
authors.lastname: Wu
authors.affiliation: Affiliations of authors: Department of Environmental and Occupational Health, National Cheng Kung University , Tainan , Taiwan (WCP, MJC, HJS); Department of Epidemiology (WCP, YTH) and Department of Biostatistics (YTH), Brown University , Providence, RI ; Institute of Environmental and Occupational Health Sciences (WCP) and Institute of Clinical Medicine (HIY), National Yang-Ming University , Taipei , Taiwan ; Department of Forestry and Natural Resources, National Chiayi University , Chiayi , Taiwan (CDW); Department of Environmental Health, Harvard School of Public Health , Boston, MA (CDW); National Environmental Health Research Center, National Health Research Institutes , Miaoli , Taiwan (MJC); Genomics Research Center, Academia Sinica , Taipei , Taiwan (CJC, HIY); Graduate Institute of Epidemiology and Preventive Medicine, National Taiwan University , Taipei , Taiwan (CJC).
authors.forename: Mu-Jean
authors.initials: MJ
authors.lastname: Chen
authors.affiliation: Affiliations of authors: Department of Environmental and Occupational Health, National Cheng Kung University , Tainan , Taiwan (WCP, MJC, HJS); Department of Epidemiology (WCP, YTH) and Department of Biostatistics (YTH), Brown University , Providence, RI ; Institute of Environmental and Occupational Health Sciences (WCP) and Institute of Clinical Medicine (HIY), National Yang-Ming University , Taipei , Taiwan ; Department of Forestry and Natural Resources, National Chiayi University , Chiayi , Taiwan (CDW); Department of Environmental Health, Harvard School of Public Health , Boston, MA (CDW); National Environmental Health Research Center, National Health Research Institutes , Miaoli , Taiwan (MJC); Genomics Research Center, Academia Sinica , Taipei , Taiwan (CJC, HIY); Graduate Institute of Epidemiology and Preventive Medicine, National Taiwan University , Taipei , Taiwan (CJC).
authors.forename: Yen-Tsung
authors.initials: YT
authors.lastname: Huang
authors.affiliation: Affiliations of authors: Department of Environmental and Occupational Health, National Cheng Kung University , Tainan , Taiwan (WCP, MJC, HJS); Department of Epidemiology (WCP, YTH) and Department of Biostatistics (YTH), Brown University , Providence, RI ; Institute of Environmental and Occupational Health Sciences (WCP) and Institute of Clinical Medicine (HIY), National Yang-Ming University , Taipei , Taiwan ; Department of Forestry and Natural Resources, National Chiayi University , Chiayi , Taiwan (CDW); Department of Environmental Health, Harvard School of Public Health , Boston, MA (CDW); National Environmental Health Research Center, National Health Research Institutes , Miaoli , Taiwan (MJC); Genomics Research Center, Academia Sinica , Taipei , Taiwan (CJC, HIY); Graduate Institute of Epidemiology and Preventive Medicine, National Taiwan University , Taipei , Taiwan (CJC).
authors.forename: Chien-Jen
authors.initials: CJ
authors.lastname: Chen
authors.affiliation: Affiliations of authors: Department of Environmental and Occupational Health, National Cheng Kung University , Tainan , Taiwan (WCP, MJC, HJS); Department of Epidemiology (WCP, YTH) and Department of Biostatistics (YTH), Brown University , Providence, RI ; Institute of Environmental and Occupational Health Sciences (WCP) and Institute of Clinical Medicine (HIY), National Yang-Ming University , Taipei , Taiwan ; Department of Forestry and Natural Resources, National Chiayi University , Chiayi , Taiwan (CDW); Department of Environmental Health, Harvard School of Public Health , Boston, MA (CDW); National Environmental Health Research Center, National Health Research Institutes , Miaoli , Taiwan (MJC); Genomics Research Center, Academia Sinica , Taipei , Taiwan (CJC, HIY); Graduate Institute of Epidemiology and Preventive Medicine, National Taiwan University , Taipei , Taiwan (CJC).
authors.forename: Huey-Jen
authors.initials: HJ
authors.lastname: Su
authors.affiliation: Affiliations of authors: Department of Environmental and Occupational Health, National Cheng Kung University , Tainan , Taiwan (WCP, MJC, HJS); Department of Epidemiology (WCP, YTH) and Department of Biostatistics (YTH), Brown University , Providence, RI ; Institute of Environmental and Occupational Health Sciences (WCP) and Institute of Clinical Medicine (HIY), National Yang-Ming University , Taipei , Taiwan ; Department of Forestry and Natural Resources, National Chiayi University , Chiayi , Taiwan (CDW); Department of Environmental Health, Harvard School of Public Health , Boston, MA (CDW); National Environmental Health Research Center, National Health Research Institutes , Miaoli , Taiwan (MJC); Genomics Research Center, Academia Sinica , Taipei , Taiwan (CJC, HIY); Graduate Institute of Epidemiology and Preventive Medicine, National Taiwan University , Taipei , Taiwan (CJC).
authors.forename: Hwai-I
authors.initials: HI
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D000393:Air Pollutants / Q000009:adverse effects*; D000410:Alanine Transaminase / Q000097:blood / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000453:epidemiology* / Q000209:etiology* / Q000401:mortality / Q000821:virology; D015986:Confounding Factors, Epidemiologic; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D019694:Hepatitis B, Chronic / Q000150:complications; D019698:Hepatitis C, Chronic / Q000150:complications; D006801:Humans; D015994:Incidence; D008113:Liver Neoplasms / Q000201:enzymology / Q000453:epidemiology* / Q000209:etiology* / Q000401:mortality / Q000821:virology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010316:Particle Size; D052638:Particulate Matter / Q000009:adverse effects*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012042:Registries; D012306:Risk; D013624:Taiwan / Q000453:epidemiology
chemical_list: D000393:Air Pollutants; D052638:Particulate Matter; D000410:Alanine Transaminase