title: Pesticide exposure and hepatocellular carcinoma risk: A case-control study using a geographic information system (GIS) to link SEER-Medicare and California pesticide data.
abstract: BACKGROUND
  Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, is associated with low survival. U.S. studies examining self-reported pesticide exposure in relation to HCC have demonstrated inconclusive results. We aimed to clarify the association between pesticide exposure and HCC by implementing a novel data linkage between Surveillance, Epidemiology, and End Results (SEER)-Medicare and California Pesticide Use Report (PUR) data using a geographic information system (GIS).
  
  
  METHODS
  Controls were frequency-matched to HCC cases diagnosed between 2000 and 2009 in California by year, age, race, sex, and duration of residence in California. Potential confounders were extracted from Medicare claims. From 1974 to 2008, pounds (1 pound represents 0.45 kg) of applied organophosphate, organochlorine, and carbamate pesticides provided in PURs were aggregated to the ZIP Code level using area weighting in a GIS. ZIP Code exposure estimates were linked to subjects using Medicare-provided ZIP Codes to calculate pesticide exposure. Agricultural residents were defined as living in ZIP Codes with a majority area intersecting agricultural land cover according to the 1992, 2001, and 2006 National Land Cover Database (NLCD) rasters. Multivariable conditional logistic regression was used to estimate the association between pesticide exposure and HCC.
  
  
  RESULTS
  Among California residents of agriculturally intensive areas, previous annual ZIP Code-level exposure to over 14.53 kg/km(2) of organochlorine pesticides (75(th) percentile among controls) was associated with an increased risk of HCC after adjusting for liver disease and diabetes (adjusted odds ratio [OR] 1.87, 95% confidence interval [CI] 1.17, 2.99; p=0.0085). ZIP Code-level organochlorines were significantly associated with an increased risk of HCC among males (adjusted OR 2.76, 95% CI 1.58, 4.82; p=0.0004), but not associated with HCC among females (adjusted OR 0.83, 95% CI 0.35, 1.93; p=0.6600) (interaction p=0.0075).
  
  
  CONCLUSIONS
  This is the first epidemiologic study to use GIS-based exposure estimates to study pesticide exposure and HCC. Our results suggest that organochlorine pesticides are associated with an increase in HCC risk among males but not females.
authors.affiliation: Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, 130 De Soto Street, Pittsburgh, PA 15261, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, United States; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, United States. Electronic address: tvopham@hsph.harvard.edu.
authors.forename: Trang
authors.initials: T
authors.lastname: VoPham
authors.affiliation: Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, 130 De Soto Street, Pittsburgh, PA 15261, United States. Electronic address: brooks@edc.pitt.edu.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Brooks
authors.affiliation: Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, 130 De Soto Street, Pittsburgh, PA 15261, United States; Division of Cancer Control and Population Sciences, University of Pittsburgh Cancer Institute, 5150 Centre Avenue, Pittsburgh, PA 15232, United States. Electronic address: yuanj@upmc.edu.
authors.forename: Jian-Min
authors.initials: JM
authors.lastname: Yuan
authors.affiliation: Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, 130 De Soto Street, Pittsburgh, PA 15261, United States. Electronic address: eot1@pitt.edu.
authors.forename: Evelyn O
authors.initials: EO
authors.lastname: Talbott
authors.affiliation: Spatial Sciences Institute, University of Southern California, 3616 Trousdale Parkway AHF B55, Los Angeles, CA 90089, United States. Electronic address: druddell@usc.edu.
authors.forename: Darren
authors.initials: D
authors.lastname: Ruddell
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, United States; Department of Environmental Health, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, United States. Electronic address: rejch@channing.harvard.edu.
authors.forename: Jaime E
authors.initials: JE
authors.lastname: Hart
authors.affiliation: Division of General Internal Medicine, University of Pittsburgh School of Medicine, 200 Meyran Avenue Suite 200, Pittsburgh, PA 15213, United States. Electronic address: changj@pitt.edu.
authors.forename: Chung-Chou H
authors.initials: CC
authors.lastname: Chang
authors.affiliation: Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, 130 De Soto Street, Pittsburgh, PA 15261, United States; Division of Cancer Control and Population Sciences, University of Pittsburgh Cancer Institute, 5150 Centre Avenue, Pittsburgh, PA 15232, United States. Electronic address: jwepid@comcast.net.
authors.forename: Joel L
authors.initials: JL
authors.lastname: Weissfeld
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D002140:California / Q000453:epidemiology; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000453:epidemiology*; D016022:Case-Control Studies; D004781:Environmental Exposure / Q000009:adverse effects / Q000032:analysis*; D005260:Female; D040362:Geographic Information Systems; D006801:Humans; D008113:Liver Neoplasms / Q000139:chemically induced / Q000453:epidemiology*; D008297:Male; D006278:Medicare; D010575:Pesticides / Q000032:analysis* / Q000633:toxicity; D018426:SEER Program; D014481:United States
chemical_list: D010575:Pesticides
keywords: Case-control study; Epidemiology; Geographic information system; Liver cancer; Pesticide