Microplastics and Obesity in the MEC Adiposity Phenotype Study - PROJECT SUMMARY / ABSTRACT This application is being submitted in response to PAR-21-341 “Exploratory Grants in Cancer Control (R21 Clinical Trial Optional)”. Human exposure to microplastics (MP) (size: 1µm-5mm) and nanoplastics (NP) (<1µm) is ubiquitous and likely to increase before adequate mitigation strategies are implemented. Evidence suggests that MPs of size <20 µm can penetrate organs, and MPs <10 µm can penetrate cell membranes in exposed cells or laboratory animals. MPs and several of their additives have been shown to be obesogenic in animal models through inflammation, immunological response, endocrine disruption, alteration of lipid and energy metabolism, gut microbiome dysbiosis and other dysregulations. Despite this, little is known about the toxic effects of MP/NP in humans. In this two-year grant, we propose to initiate an epidemiological investigation of the role of circulating MP in excess adiposity (measured by imaging), metabolic health (measured by biomarkers and omics), inflammation biomarkers, and gut microbiome, as an initial step in investigating their role in cancer etiology. We will use stored serum samples collected as part of the Multiethnic Cohort (MEC) Adiposity Phenotype Study (APS) (P01 CA168530) among a subset of uniquely heterogeneous and well- characterized participants in Hawai’i and Los Angeles, a population highly exposed to MP. We already showed substantial presence of MP in ten QC samples collected in 2013-2016 as part of APS and demonstrated our ability to assess NP by flow cytometry. In Aim 1, we will determine by flow cytometry the size and number of NP particles, and by Raman micro-spectroscopy the type of MP particles, present in the serum of 500, randomly-selected, MEC APS participants (50 from each of the ten sex, race groups). Intra-individual variation over a year, correlation with MP in stool, and temporal trends in exposure over three decades will be examined on subsets. Aim 2 will examine the association of these MP/NP measures with sex, race/ethnicity, education, neighborhood SES, dietary intake, lifestyle (smoking, physical activity), BMI, DXA-measured total and regional adiposity, MRI-measured visceral and liver fat, metabolic, hormonal and inflammatory biomarkers, fecal microbiome and plasma lipidomics. This work will provide critical initial information on which to expand our investigation of MP and NP with metabolic health to larger numbers of stored APS samples, as well as to investigate the association of MP and NP with risk of colorectal, lung, breast and prostate cancers in stored blood samples from nested case-control studies in the MEC populations. R01-level funding will be sought as our next step. This research will help to improve our understanding of internal exposure to MP, and NP of various sizes, and their relationships to race/ethnicity, excess adiposity, ectopic fat, lifestyle and biology. Knowledge of environmental causes of obesity will be highly valuable to establish regulatory policies and recommend individual behaviors to reduce the risk of thirteen cancers known to be related to obesity.
