Lipid adjustment in the analysis of environmental contaminants and human health risks

Enrique F. Schisterman, Brian W. Whitcomb, Germaine M. Buck Louis, Thomas A. Louis

Research output: Contribution to journalArticlepeer-review

275 Scopus citations


The literature on exposure to lipophilic agents such as plychlorinated biphenyls (PCBs) in conflicting, posing challenges for the interpretation of potential human health risks. Laboratory variation in quantifying PCBs may account for some of the conflicting study results. For example, for quantification purposes, blood is often used as a proxy for adipose tissue, which makes it necessary to model serum lipids when assessing health risks of PCBs. Using a simulation study, we evaluated four statistical models (unadjusted, standardized, adjusted, and two-stage) for the analysis of PCB exposure, serum lipids, and health outcome risk (breast cancer). We applied eight candidate true causal scenarios, depicted by directed acyclic graphs, to illustrate the ramifications of mis-specification of underlying assumptions when interpreting results. Statistical models that deviated from underlying causal assumptions generated biased results. Lipid standardization, or the division of serum concentrations by serum lipids, was observed to be highly prone to bias. We conclude that investigators must consider biology, biologic medium (e.g., nonfasting blood samples), laboratory measurement, and other underlying modeling assumptions when devising a statistical plan for assessing health outcomes in relation to environmental exposures.

Original languageEnglish (US)
Pages (from-to)853-857
Number of pages5
JournalEnvironmental health perspectives
Issue number7
StatePublished - Jul 2005


  • Causal modeling
  • Directed acyclic graphs
  • Organochlorines
  • Polychlorinated biphenyls
  • Risk estimation
  • Serum lipids

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis


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