Assessment of Grouped Weighted Quantile Sum Regression for Modeling Chemical Mixtures and Cancer Risk
Individuals are exposed to a large number of diverse environmental chemicals simultaneously and the evaluation of multiple chemical exposures is important for identifying cancer risk factors. The measurement of a large number of chemicals (the exposome) in epidemiologic studies is allowing for a mor...
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doaj-56d91efde66f4ac3b3e192e39cf89ef12021-01-10T00:03:01ZengMDPI AGInternational Journal of Environmental Research and Public Health1661-78271660-46012021-01-011850450410.3390/ijerph18020504Assessment of Grouped Weighted Quantile Sum Regression for Modeling Chemical Mixtures and Cancer RiskDavid C. Wheeler0Salem Rustom1Matthew Carli2Todd P. Whitehead3Mary H. Ward4Catherine Metayer5Department of Biostatistics, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298-0032, USADepartment of Biostatistics, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298-0032, USADepartment of Biostatistics, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298-0032, USADivision of Epidemiology/Biostatistics, University of California, Berkeley School of Public Health, Berkeley, CA 94704-7394, USAOccupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20850, USADivision of Epidemiology/Biostatistics, University of California, Berkeley School of Public Health, Berkeley, CA 94704-7394, USAIndividuals are exposed to a large number of diverse environmental chemicals simultaneously and the evaluation of multiple chemical exposures is important for identifying cancer risk factors. The measurement of a large number of chemicals (the exposome) in epidemiologic studies is allowing for a more comprehensive assessment of cancer risk factors than was done in earlier studies that focused on only a few chemicals. Empirical evidence from epidemiologic studies shows that chemicals from different chemical classes have different magnitudes and directions of association with cancers. Given increasing data availability, there is a need for the development and assessment of statistical methods to model environmental cancer risk that considers a large number of diverse chemicals with different effects for different chemical classes. The method of grouped weighted quantile sum (GWQS) regression allows for multiple groups of chemicals to be considered in the model such that different magnitudes and directions of associations are possible for each group of chemicals. In this paper, we assessed the ability of GWQS regression to estimate exposure effects for multiple chemical groups and correctly identify important chemicals in each group using a simulation study. We compared the performance of GWQS regression with WQS regression, the least absolute shrinkage and selection operator (lasso), and the group lasso in estimating exposure effects and identifying important chemicals. The simulation study results demonstrate that GWQS is an effective method for modeling exposure to multiple groups of chemicals and compares favorably with other methods used in mixture analysis. As an application, we used GWQS regression in the California Childhood Leukemia Study (CCLS), a population-based case-control study of childhood leukemia in California to estimate exposure effects for many chemical classes while also adjusting for demographic factors. The CCLS analysis found evidence of a positive association between exposure to the herbicide dacthal and an increased risk of childhood leukemia.https://www.mdpi.com/1660-4601/18/2/504mixturesenvironmentcancerchemicals |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
David C. Wheeler Salem Rustom Matthew Carli Todd P. Whitehead Mary H. Ward Catherine Metayer |
spellingShingle |
David C. Wheeler Salem Rustom Matthew Carli Todd P. Whitehead Mary H. Ward Catherine Metayer Assessment of Grouped Weighted Quantile Sum Regression for Modeling Chemical Mixtures and Cancer Risk International Journal of Environmental Research and Public Health mixtures environment cancer chemicals |
author_facet |
David C. Wheeler Salem Rustom Matthew Carli Todd P. Whitehead Mary H. Ward Catherine Metayer |
author_sort |
David C. Wheeler |
title |
Assessment of Grouped Weighted Quantile Sum Regression for Modeling Chemical Mixtures and Cancer Risk |
title_short |
Assessment of Grouped Weighted Quantile Sum Regression for Modeling Chemical Mixtures and Cancer Risk |
title_full |
Assessment of Grouped Weighted Quantile Sum Regression for Modeling Chemical Mixtures and Cancer Risk |
title_fullStr |
Assessment of Grouped Weighted Quantile Sum Regression for Modeling Chemical Mixtures and Cancer Risk |
title_full_unstemmed |
Assessment of Grouped Weighted Quantile Sum Regression for Modeling Chemical Mixtures and Cancer Risk |
title_sort |
assessment of grouped weighted quantile sum regression for modeling chemical mixtures and cancer risk |
publisher |
MDPI AG |
series |
International Journal of Environmental Research and Public Health |
issn |
1661-7827 1660-4601 |
publishDate |
2021-01-01 |
description |
Individuals are exposed to a large number of diverse environmental chemicals simultaneously and the evaluation of multiple chemical exposures is important for identifying cancer risk factors. The measurement of a large number of chemicals (the exposome) in epidemiologic studies is allowing for a more comprehensive assessment of cancer risk factors than was done in earlier studies that focused on only a few chemicals. Empirical evidence from epidemiologic studies shows that chemicals from different chemical classes have different magnitudes and directions of association with cancers. Given increasing data availability, there is a need for the development and assessment of statistical methods to model environmental cancer risk that considers a large number of diverse chemicals with different effects for different chemical classes. The method of grouped weighted quantile sum (GWQS) regression allows for multiple groups of chemicals to be considered in the model such that different magnitudes and directions of associations are possible for each group of chemicals. In this paper, we assessed the ability of GWQS regression to estimate exposure effects for multiple chemical groups and correctly identify important chemicals in each group using a simulation study. We compared the performance of GWQS regression with WQS regression, the least absolute shrinkage and selection operator (lasso), and the group lasso in estimating exposure effects and identifying important chemicals. The simulation study results demonstrate that GWQS is an effective method for modeling exposure to multiple groups of chemicals and compares favorably with other methods used in mixture analysis. As an application, we used GWQS regression in the California Childhood Leukemia Study (CCLS), a population-based case-control study of childhood leukemia in California to estimate exposure effects for many chemical classes while also adjusting for demographic factors. The CCLS analysis found evidence of a positive association between exposure to the herbicide dacthal and an increased risk of childhood leukemia. |
topic |
mixtures environment cancer chemicals |
url |
https://www.mdpi.com/1660-4601/18/2/504 |
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