Lipid adjustment in the analysis of environmental contaminants and human health risks.
The literature on exposure to lipophilic agents such as polychlorinated biphenyls (PCBs) is 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 misspecification 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.
Division of Epidemiology, Statistics and Prevention Research, National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Rockville, Maryland 20852, USA. schistee@mail.nih.gov
Enrique F
EF
Schisterman
Brian W
BW
Whitcomb
Germaine M Buck
GM
Louis
Thomas A
TA
Louis
D015982:Bias; D003198:Computer Simulation; D004781:Environmental Exposure; D004784:Environmental Monitoring; D004785:Environmental Pollutants / Q000097:blood* / Q000633:toxicity; D008055:Lipids / Q000097:blood*; D008954:Models, Biological; D015233:Models, Statistical; D011078:Polychlorinated Biphenyls / Q000097:blood* / Q000633:toxicity
D004785:Environmental Pollutants; D008055:Lipids; D011078:Polychlorinated Biphenyls