Skip to Main Content

An official website of the United States government

Aflatoxin, Polycyclic Aromatic Hydrocarbons, Heavy metals and DNA Methylation in Hepatocellular Carcinoma

Principal Investigator
Name
HuiChen Wu
Degrees
Dr. PH, MS
Institution
Columbia University
Position Title
Assistant Professor
Email
About this CDAS Project
Study
PLCO (Learn more about this study)
Project ID
2022-0003
Initial CDAS Request Approval
Sep 7, 2022
Title
Aflatoxin, Polycyclic Aromatic Hydrocarbons, Heavy metals and DNA Methylation in Hepatocellular Carcinoma
Summary
In the US, incidence rates of hepatocellular carcinoma (HCC) have tripled over the past two decades and continue to rise. Upwards of 40.5% of US HCC cases are unexplained by the common risk factors, including hepatitis B and C virus (HBV/HCV), alcohol abuse, and obesity/diabetes. Additionally, there is an increasing concern about exposure to carcinogens such as aflatoxins, polycyclic aromatic hydrocarbons (PAHs), and toxic heavy metals in HCC globally and the US. We previously conducted several nested case-control studies in Taiwan, where the incidence of HCC is high. We reported that higher aflatoxin-and PAH-albumin adducts were associated with an increased risk of HCC. Heavy metals such as arsenic and cadmium are established carcinogens; however, epidemiological evidence on HCC is limited. Increasing evidence suggests that environmental exposure to aflatoxin, PAH, or arsenic alter distinct DNA methylation or “footprints” in blood DNA. However, the exposures associated with DNA methylation changes in HCC risk have not been studied. Our study aims to use a large nested case-control study with several US cohorts to examine the role of toxic exposure, and associated epigenetic changes in HCC risk. We will also examine the associations by racial/ethnic groups and socioeconomic status and explore the interactions with other common risk factors, including obesity, and alcohol drinking.
Aims

Hypothesis: We hypothesize that 1) cases will have higher levels of environmental exposures including aflatoxin- and PAH-albumin adducts and heavy metals (arsenic and cadmium) in blood than controls, 2) the associations of exposure and HCC risk will differ by race/ethnicity or socioeconomic factors, and 3) exposure associated DNA methylation markers will differ between cases and control .
We are in the process of creating a consortium of nested case control studies with an approximate sample size of 915 HCC cases and 915 matched controls within 4 cohorts. These aims will be conducted within a pool analysis of approved studies. We aim to:
AIM 1: Examine the effect of aflatoxins on HCC risk. We will measure aflatoxin-albumin adducts, and examine the independent effect in HCC risk.
AIM 2: Examine the effect of polycyclic aromatic hydrocarbons (PAHs) on HCC risk. We will measure PAHs-albumin adducts, and examine the independent effect in HCC risk
AIM 3: Examine the effect of heavy metals on HCC risk. We will measure several heavy metals panels including total arsenic, arsenic species, and cadmium in blood and examine the independent effect in HCC risk.
AIM 4: Examine the effect of DNA methylation associated with a) HCC risk, b) aflatoxin-albumin adducts, c) PAH-albumin adducts, and d) heavy metals. We will measure the methylation profile using HumanMethylationEPIC BeadChips.
Aim 5. Examine heterogeneity in these associations by race/ethnicity or socioeconomic status, and other known risk factors

Collaborators

HuiChen Wu (Columbia University Irving Medical Center)
Genkinger, Jeanine M (Columbia University Irving Medical Center)
Santella, Regina M (Columbia University Irving Medical Center)
Navas-Acien, Ana (Columbia University Irving Medical Center)