Endotoxin and Lung Cancer: Separating Health Worker Bias from Biologic Mechanism

Details

• Personal Author:
  Applebaum KM
• Description:
  BACKGROUND: In occupational settings, workers may be exposed to endotoxin, a component of Gram-negative bacteria found on organic materials. In the Shanghai female textile workers study, it was previously reported that with increasing endotoxin exposure, risk of lung cancer decreased. We questioned whether this inverse association may be explained by factors that influence an immunological response (e.g., reproductive factors). We also questioned if the results could be fully or partially explained by left truncation, which occurs when enrolling subjects for study after they had been hired earlier in time. We also investigated more tightly controlling for the healthy worker survivor effect (HWSE), a source of downward bias. METHODS: The Shanghai female textile workers study included 267,400 employees of the Shanghai Textile Industry Bureau enrolled 1989-1991. Follow-up was initially through 1998 with 641 lung cancer cases identified. Follow-up was repeatedly extended, with approximately 1500 lung cancer cases at last count. At baseline, all women completed a questionnaire about reproductive factors. To study reproductive factors, traditional Cox proportional hazards regression models were used. For analyses of occupational exposures, a case-cohort design was employed using all cancer cases and a subcohort of controls (n=3,188); regression models accounted for sampling. In examining left truncation and HWSE, analyses changed analytical timelines and applied standard and structural nested accelerated failure time models (SNAFT). A simulation study examined the direction of the bias from left truncation. RESULTS: Analyses indicated that both biological and methodological factors could influence the inverse association. Reproductive factors modified the association with lung cancer in this endotoxin-exposed cohort. Also, both the simulation study and analyses from the Shanghai study indicated that left truncation induced a downward bias. After accounting for left truncation, an inverse association remained in those whose date of hire was within 50 years of the start of follow-up while endotoxin was associated with an increased risk of lung cancer risk among those hired more than 50 years before study baseline. The Shanghai study will serve as an important example of when application of SNAFT is not needed. CONCLUSIONS: Demonstrating the strong influence of left truncation was notable as this issue had not previously been given much consideration in occupational epidemiology. Reporting the 'endotoxin paradox' with lung cancer risk decreasing and later increasing over time may influence the way endotoxin and lung cancer is studied. The benefit of these findings will be longer-term as it will take time for other researchers to integrate such changes, yet as their applications become more widespread, analyses will better reflect the complex relationships between occupational exposures and chronic disease, yielding a greater understanding of the risks workers face. CAREER DEVELOPMENT: This award was instrumental in facilitating Dr. Applebaum to develop her research career. Activities related to this grant contributed to her earning a tenure-track faculty position and being awarded an R01. [Description provided by NIOSH]
• Subjects:
  Chronic Disease Cohort Studies Endotoxins Lung Lung Diseases Neoplasms Occupational Exposure Occupational Health Respiratory System Respiratory Tract Diseases Safety Textile Industry Women

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• Keywords:
  Bacteria Chronic Diseases Cohort Studies Lung Cancer Occupational Exposure Textile Workers
• Series:
  Grant Final Reports
• Publisher:
  National Institute for Occupational Safety and Health
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Final Grant Report
• Place as Subject:
  District of Columbia ; Massachusetts ; OSHA Region 1 ; OSHA Region 3
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  OEP - Office of Extramural Programs
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  1-14
• NIOSHTIC Number:
  nn:20056547
• NTIS Accession Number:
  PB2019-101399
• Citation:
  Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, K01-OH-009390, 2013 Nov; :1-14
• Contact Point Address:
  Katie M. Applebaum, ScD, MSPH, Assistant Professor, Department of Environmental and Occupational Health, George Washington University School of Public Health and Health Services, 2100 M Street NW, Suite 203A, Washington, DC 20037
• Email:
  kapplebaum@gwu.edu
• Federal Fiscal Year:
  2014
• NORA Priority Area:
  Manufacturing
• Performing Organization:
  Boston University Medical Campus
• Peer Reviewed:
  False
• Start Date:
  20080801
• Source Full Name:
  National Institute for Occupational Safety and Health
• End Date:
  20130731
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:1377e7dd349fb51cb71def5c394a34038b5db4dce6fc5a092848d3a2eebc2a24b6d8076fe4d7e57ff36836b146e3f720987fddc02850dc8aaccb0a6f892972f9
• Download URL:
  https://stacks.cdc.gov/view/cdc/218900/cdc_218900_DS1.pdf
• File Type:
  [PDF - 673.20 KB ]