Benzene exposure-response and risk of lymphoid neoplasms in Chinese workers: A multicenter case-cohort study

Am J Ind Med. 2020 Sep;63(9):741-754. doi: 10.1002/ajim.23142. Epub 2020 May 31.

Abstract

Background: While international agreement supports a causal relationship of benzene exposure with acute myeloid leukemia, there is debate about benzene and lymphoid neoplasm risks.

Methods: In a case-cohort study with follow-up of 110 631 Chinese workers during 1972-1999, we evaluated benzene exposure-response for non-Hodgkin lymphoma (NHL), lymphoid leukemias (LL), acute lymphocytic leukemia (ALL), and total lymphoid neoplasms (LN). We estimated benzene exposures using state-of-the-art hierarchical modeling of occupational factors calibrated with historical routine measurements and evaluated cumulative exposure-response using Cox regression.

Results: NHL and other specified LN were increased in exposed vs unexposed workers. However, there was no evidence of exposure-response for NHL or other specified LN. Based on a linear exposure-response, relative risks at 100 parts per million-years (RR at 100 ppm-years) for cumulative benzene exposure using a 2-year lag (exposure at least 2 years before the time at risk) were 1.05 for NHL (95 percent confidence interval (CI) = 0.97, 1.27; 32 cases), 1.11 for LL (95% CI < 0, 1.66; 12 cases), 1.21 for ALL (95% CI < 0, 3.53; 10 cases), and 1.02 for total LN (95% CI < 0, 1.16; 49 cases). No statistically significant exposure-response trends were apparent for these LN for 2 to <10-year or ≥10-year lags. NHL risks were not significantly modified by sex, age, or year at first exposure, attained age, or time since exposure.

Conclusion: Given the study strengths and limitations, we found little evidence of exposure-response for benzene and NHL, LL, ALL, or total LN, although NHL and other specified LN were increased in exposed vs unexposed individuals.

Keywords: benzene; case-cohort study; leukemia; lymphoid; non-Hodgkin lymphoma; occupational exposure.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adolescent
  • Adult
  • Benzene / analysis*
  • Benzene / toxicity
  • China / epidemiology
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Leukemia, Lymphoid / chemically induced
  • Leukemia, Lymphoid / epidemiology*
  • Lymphoma / chemically induced
  • Lymphoma / epidemiology*
  • Lymphoma, Non-Hodgkin / chemically induced
  • Lymphoma, Non-Hodgkin / epidemiology
  • Male
  • Middle Aged
  • Occupational Diseases / chemically induced
  • Occupational Diseases / epidemiology*
  • Occupational Exposure / adverse effects
  • Occupational Exposure / analysis*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / chemically induced
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / epidemiology
  • Proportional Hazards Models
  • Regression Analysis
  • Risk
  • Young Adult

Substances

  • Benzene