||5R21CA238370-02 Interpret this number
||Virginia Commonwealth University
||Modeling Multiple Environmental Exposures and Childhood Leukemia Risk
Incidence for many cancers is suspected to be associated with chemicals through environmental routes of
exposure. Individuals are exposed to a large number of diverse environmental chemicals simultaneously and
evaluation of multiple chemical exposures is important for identifying cancer risk factors. Increasingly,
exposures are being measured for a large number of chemicals in epidemiologic studies to allow for a more
comprehensive assessment of cancer risk factors in the exposome. However, most existing studies of
environmental chemical exposures and cancer use a single-chemical approach that evaluates chemicals
independently as risk factors. Traditional statistical methods used in existing studies are significantly
challenged by the typically strong correlation observed among many environmental chemical exposures, as
well as other environmental and socioeconomic variables. There is a need for development and assessment of
statistical methods to model environmental cancer risk that consider a large number of diverse chemicals with
different effects for different chemical classes. The specific aims of this research are 1) to develop more
comprehensive exposure risk models and apply them to a case-control study of childhood leukemia in
California that contains concentrations measured for a large number of diverse chemicals, 2) to account for
uncertainty associated with imputing chemical concentrations below the limit of detection when estimating
chemical mixture effect, and 3) to account for neighborhood socioeconomic status and residual confounding
when estimating chemical exposure effects. The study of childhood leukemia will benefit from environmental
chemical risk analysis because it is a cancer with an unclear etiology and established risk factors that account
for only a small proportion of the total annual cases in the United States. The expected outcomes of this
research will be 1) new statistical approaches to model environmental cancer risk that consider environmental
exposures more comprehensively while also accounting for uncertainty related to missing data, and 2) an
evaluation of the effects of exposure to chemicals from many chemical classes and an identification of the
important chemicals for childhood leukemia. The significance of this research is two-fold. First, the
development and evaluation of new statistical approaches to risk analysis that consider multiple diverse
environmental exposures while accounting for uncertainty will advance the field of environmental epidemiology
research. Second, this will be the first environmental risk analysis of a case-control study of childhood
leukemia that estimates effects for different chemical classes using a large number of correlated chemical
exposures while also adjusting for known demographic risk factors at the household and neighborhood level
and accounting for uncertainty related to missing data. The methodological approaches developed in this work
will be applicable to many other cancers associated with multiple environmental exposures of differing types.
Assessment of Grouped Weighted Quantile Sum Regression for Modeling Chemical Mixtures and Cancer Risk.
, Rustom S.
, Carli M.
, Whitehead T.P.
, Ward M.H.
, Metayer C.
International journal of environmental research and public health, 2021-01-09; 18(2), .