AS697 - Air pollution adductomics and liver cancer risk

Investigator Names and Contact Information

Trang VoPham (tvopham@fredhutch.org)

Eric Whitsel (eric_whitsel@med.unc.edu)

Introduction/Intent

 Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and is associated with low survival. Emerging evidence suggests that particulate matter air pollution <2.5 microns in diameter (PM_2.5) is a non-viral factor that may increase the risk of developing HCC. PM_2.5, such as from motor vehicles, is a ubiquitous environmental exposure comprised of complex mixtures of chemicals (e.g., aldehydes and benzene). Although population-based studies have shown positive associations between ambient residence-based PM_2.5 measures and liver cancer risk, important research gaps remain: to date, no epidemiologic studies have examined PM_2.5 exposure using biomarkers. We therefore propose a case-control feasibility study to measure aldehyde and benzene albumin adducts (50 µL of serum at baseline among 18 HCC cases and 72 non-HCC controls in the Women's Health Initiative (WHI) Observational Study (OS) and Clinical Trials (CT). We will examine participants who were never smokers without evidence of prior hepatitis B or C virus (HBV; HCV) infection. The Specific Aims are to quantify the associations between 1) ambient PM_2.5 concentrations and serum concentrations of aldehyde / benzene albumin adducts and in turn, 2) those serum concentrations and HCC risk. We will apply novel Cys³⁴ adductomics methods to measure serum biomarkers and use high-resolution geospatial modeling to measure residential air pollution. This feasibility study will benefit cancer research through the incorporation of novel omics technologies to more precisely estimate the biological effects of personal exposure to environmental pollutants. Further, this proposal will provide meaningful insights by demonstrating the feasibility of conducting Cys³⁴ adductomics (and other) analyses in WHI and providing critical preliminary data that will inform the development of future studies with larger sample sizes (such as pooled studies across multiple cohorts) as HCC is a relatively rare outcome and studies that will examine other biomarkers of exposure.

The Specific Aims of this study are:

 Aim 1: Quantify the associations between ambient PM_2.5 concentrations and serum concentrations of aldehyde / benzene albumin adducts.

Hypothesis: Higher ambient PM_2.5 concentrations will be associated with higher serum aldehyde and benzene albumin adduct concentrations.

Aim 2: Quantify the associations between aldehyde / benzene albumin adducts and HCC risk.

Hypothesis: Higher serum aldehyde and benzene albumin adduct concentrations will be associated with increased risk of HCC.