title: Pesticide exposure and liver cancer: a review.
abstract: To review the epidemiologic literature examining pesticide exposure and liver cancer incidence.
  
  
  
  A search of the MEDLINE and Embase databases was conducted in October 2015. Eligibility criteria included examining hepatocellular carcinoma (HCC) or primary liver cancer, pesticides as an exposure of interest, and individual-level incidence. The review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
  
  
  
  Forty-eight papers were assessed for eligibility and 15 studies were included in the review. The majority of studies were conducted in China and Egypt (n = 8), used a case-control design (n = 14), and examined HCC (n = 14). Most studies showed no association between self-reported and/or occupational exposure to pesticides and liver cancer risk. Six studies demonstrated statistically significant positive associations, including three biomarker-based studies (two using pre-diagnostic sera) that reported higher serum levels of dichlorodiphenyltrichloroethane (DDT) were associated with increased HCC risk. Studies indirectly measuring pesticide exposure using self-reported exposure, occupation, job-exposure matrices, or geographic residence demonstrated inconsistent results. These studies were limited by exposure assessment methods, lack of confounder information, minimal case confirmation, selection bias, and/or over-adjustment.
  
  
  
  There is mixed evidence suggesting a possible association between specific pesticides and HCC risk, with the strongest evidence observed in biomarker-based studies. In particular, organochlorine pesticides, including DDT, may increase HCC risk. Future research should focus on improved pesticide exposure assessment methods, potentially incorporating multiple approaches including biomonitoring while considering the chemicals of interest, historical exposure to address latency periods, and examining specific chemicals and exposure pathways.
authors.affiliation: Department of Epidemiology, Harvard T. H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA. tvopham@hsph.harvard.edu.|Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA, 02115, USA. tvopham@hsph.harvard.edu.
authors.forename: Trang
authors.initials: T
authors.lastname: VoPham
authors.affiliation: Slone Epidemiology Center, Boston University, 1010 Commonwealth Avenue, 4th Floor, Boston, MA, 02215, USA.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Bertrand
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA, 02115, USA.|Department of Environmental Health, Harvard T. H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA.
authors.forename: Jaime E
authors.initials: JE
authors.lastname: Hart
authors.affiliation: Department of Epidemiology, Harvard T. H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA.|Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA, 02115, USA.|Department of Environmental Health, Harvard T. H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA.
authors.forename: Francine
authors.initials: F
authors.lastname: Laden
authors.affiliation: Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, 130 De Soto Street, Pittsburgh, PA, 15261, USA.
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, USA.|Division of Cancer Control and Population Sciences, University of Pittsburgh Cancer Institute, 5150 Centre Avenue, Pittsburgh, PA, 15232, USA.
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, USA.
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, USA.
authors.forename: Darren
authors.initials: D
authors.lastname: Ruddell
authors.affiliation: Division of General Internal Medicine, University of Pittsburgh School of Medicine, 200 Meyran Avenue Suite 200, Pittsburgh, PA, 15213, USA.
authors.forename: Chung-Chou H
authors.initials: CH
authors.lastname: Chang
authors.affiliation: Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, 130 De Soto Street, Pittsburgh, PA, 15261, USA.|Division of Cancer Control and Population Sciences, University of Pittsburgh Cancer Institute, 5150 Centre Avenue, Pittsburgh, PA, 15232, USA.
authors.forename: Joel L
authors.initials: JL
authors.lastname: Weissfeld
mesh_terms: D015415:Biomarkers / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology*; D002681:China / Q000453:epidemiology; D003634:DDT / Q000097:blood; D004534:Egypt / Q000453:epidemiology; D004781:Environmental Exposure / Q000009:adverse effects; D006801:Humans; D008113:Liver Neoplasms / Q000453:epidemiology*; D016273:Occupational Exposure / Q000009:adverse effects; D010575:Pesticides / Q000009:adverse effects*
chemical_list: D015415:Biomarkers; D010575:Pesticides; D003634:DDT
keywords: Epidemiology; Hepatocellular carcinoma; Liver cancer; Pesticides; Review