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Principal Investigator
Brenda Hernandez
University of Hawaii Cancer Center
Position Title
About this CDAS Project
PLCO (Learn more about this study)
Project ID
Initial CDAS Request Approval
Jan 19, 2023
Role of Cyanobacteria and cyanotoxins in liver cancer development
A nested case-control study of hepatocellular carcinoma (HCC) cases, chronic liver disease cases, and matched controls will be drawn from multiple prospective cohorts including the PLCO, the Multiethnic Cohort, and the NIH Liver Pooling Project, which consists of 15 prospective North American-based cohort studies.

Oral Cyanobacteria and other bacterial taxa will be evaluated in oral DNA samples of HCC cases, CLD cases, and matched controls by Illumina MiSeq 16S rRNA. Serum cyanotoxins (microcystin/nodularin, cylindrospermopsin, and anabaenopeptin) will be measured by validated ELISA assays in HCC cases, CLD cases, and matched controls. Cyanotoxins will also be measured in urine and oral samples in subsets of cases and controls. Tumor gene expression will be evaluated by Nanostring and compared by serum cyanotoxin levels in a subset of HCC cases with paired tumor tissue and blood.

The statistical analysis will focus on the association of oral Cyanobacteria and cyanotoxins (microcystin/nodularin, cylindrospermopsin, and anabaenopeptin) with risk of HCC and CLD.
Comparisons will be made by HCC risk factors (hepatitis B and C, excess alcohol, smoking, obesity, type 2 diabetes, hyperlipidemia) as well as dietary, occupational, recreational, and residential history.
Comparisons will also be made by race/ethnicity including Asians, Pacific Islanders, Hispanics, Blacks, and Whites.

Specific Aim 1. To evaluate the association of oral Cyanobacteria with risk of chronic liver disease and hepatocellular carcinoma

Specific Aim 2. To evaluate the association of liver cyanotoxins with risk of chronic liver disease and hepatocellular carcinoma.

Specific Aim 2. To identify tumor gene expression signatures specific to Cyanobacteria and cyanotoxin exposure.


Brenda Hernandez (University of Hawaii)
Linda Wong (University of Hawaii)
Lynne Wilkens (University of Hawaii)
Katherine McGlynn (National Cancer Institute)