Background: Primary liver cancer is the sixth most occurring cancer worldwide and the second most common cause of cancer mortality. Hepatocellular carcinoma (HCC) is the most prevalent histologic type of liver cancer, with well-established risk factors (e.g., chronic infections with hepatitis B virus or hepatitis C virus, and alcohol-related liver disease). Exposure to pesticides may also contribute to the etiology of liver cancer. The use of pesticides has increased significantly in both developed and developing countries within the last few decades. The association between pesticides and liver cancer is unclear. We conducted a systematic review and meta-analysis to investigate the relationship between exposure to pesticides (e.g.; organophosphates, organochlorines, carbamates, dichlorodiphenyltrichloroethane, dichlorodiphenyldichloroethylene, agent orange) and liver cancer incidence and mortality.

Methods: We searched PubMed and EMBASE databases using a combination of medical subject heading terms and key words for articles published before June 2016. Articles were identified as relevant if they were original studies and met the following criteria: 1) primary liver cancer was an identified outcome for risk or mortality, 2) pesticides were the main exposure of interest, 3) exposure to pesticides was assessed histologically (e.g.; blood serum) or through questionnaires, and 4) the estimates for the association between liver cancer risk/mortality and pesticide exposure were reported. Titles and abstracts meeting search criteria were reviewed and relevant full-text articles were read and analyzed independently by two researchers. We calculated the summary estimates [Odd Ratios (ORs) or Relative Risks (RR)] and 95% confidence intervals (CIs) using random-effects models. All analyses were conducted using STATA 14.0.

Results: Of 1644 articles reviewed, a total of 34 observational studies were identified as relevant and 20 were included in the meta-analysis for liver cancer risk (5 case-controls and 15 cohorts). All of the identified studies investigated HCC as the outcome; none investigated other types of liver cancer. The results showed that pesticide exposure was associated with a 73% increased risk of HCC (RRsummary:1.73, 95% CI 1.40-2.13; I2=85.9%, P=<0.001). Stratified analyses by study design showed similar results (case-control: 1.69, 95% CI 1.31-2.18; cohorts: 1.47, 95% CI 1.25-1.72). Furthermore, in analysis stratified by sex and type of pesticide similar elevated risks were observed. Analysis of articles that reported on liver cancer mortality (n=7) showed an excess in mortality from HCC for individuals exposed to pesticides.

Conclusion: The existing epidemiological data supports the hypothesis that exposure to pesticides is associated with a significant increased risk of HCC and death from liver cancer.

Citation Format: Hamdi Abdi, Jennifer Lee, Gary Ellison, Gabriel Lai, Tram Lam. Pesticides and primary liver cancer: A systematic review and meta-analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2300. doi:10.1158/1538-7445.AM2017-2300