Shanghai Health Study (2001-2009): What was learned about benzene health effects?

Crit Rev Toxicol. 2018 Mar;48(3):217-251. doi: 10.1080/10408444.2017.1401581. Epub 2017 Dec 15.


The Shanghai Health Study (SHS) was a large epidemiology study conducted as a joint effort between the University of Colorado and Fudan University in Shanghai, China. The study was funded by members of the American Petroleum Institute between 2001 and 2009 and was designed to evaluate the human health effects associated with benzene exposure. Two arms of the SHS included: an occupational-based molecular epidemiology study and several hospital-based case control studies. Consistent with historical literature, following sufficient exposure to relatively high airborne concentrations and years of exposure, the SHS concluded that exposure to benzene resulted in an increased risk of various blood and bone marrow abnormalities such as benzene poisoning, aplastic anemia (AA), myelodysplastic syndrome (MDS), and acute myeloid leukemia (AML). Non-Hodgkin lymphoma (NHL) was not significantly increased for the exposures examined in this study. Perhaps the most important contribution of the SHS was furthering our understanding of the mechanism of benzene-induced bone marrow toxicity and the importance of identifying the proper subset of MDS relevant to benzene. Investigators found that benzene-exposed workers exhibited bone marrow morphology consistent with an immune-mediated inflammatory response. Contrary to historic reports, no consistent pattern of cytogenetic abnormalities was identified in these workers. Taken together, findings from SHS provided evidence that the mechanism for benzene-induced bone marrow damage was not initiated by chromosome abnormalities. Instead, chronic inflammation, followed by an immune-mediated response, is likely to play a more significant role in benzene-induced disease initiation and progression than previously thought.

Keywords: Benzene; acute myeloid leukemia (AML); aplastic anemia; chronic myelomonocytic leukemia (CMML); exposure assessment; molecular epidemiology; myelodysplastic syndrome (MDS); non-Hodgkin lymphoma (NHL).

Publication types

  • Review
  • Video-Audio Media

MeSH terms

  • Benzene / toxicity*
  • Case-Control Studies
  • China / epidemiology
  • Environmental Exposure
  • Humans
  • Leukemia, Myeloid, Acute / chemically induced
  • Leukemia, Myeloid, Acute / epidemiology
  • Myeloproliferative Disorders / chemically induced
  • Myeloproliferative Disorders / epidemiology
  • Occupational Diseases / chemically induced*
  • Occupational Diseases / epidemiology
  • Occupational Diseases / genetics
  • Occupational Exposure / adverse effects*
  • Polymorphism, Genetic


  • Benzene