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Genetic determinants of liver cancer

Principal Investigator
Name
Sonja Berndt
Degrees
Pharm.D., Ph.D.
Institution
National Cancer Institute
Position Title
Senior Investigator
Email
About this CDAS Project
Study
PLCO (Learn more about this study)
Project ID
PLCO-1467
Initial CDAS Request Approval
Feb 5, 2024
Title
Genetic determinants of liver cancer
Summary
Liver cancer has a high mortality rate. According to data from GLOBOCAN 2020, liver cancer is the third most deadly cancer and responsible for 8.3% of all cancer-related deaths. There are two main types of primary liver cancer — hepatocellular carcinoma (HCC) and cholangiocarcinoma. Risk factors for HCC include hepatitis B and C, aflatoxin, alcohol consumption, obesity, type 2 diabetes, and smoking. Genetic factors are also thought to contribute to the development of HCC. Genome-wide association studies, largely conducted in Asian populations, have identified multiple genetic loci associated with HCC risk. Mendelian randomization analyses using genetic data have implicated potential biological pathways (e.g., telomere length) and provided additional support for suspected and known risk factors. We plan to conduct a meta-analysis of genome-wide association studies for liver cancer, perform GxE and GxG interaction analyses, conduct Mendelian randomization and polygenic score analyses to explore other risk factors, and perform further heritability, mosaicism, and bioinformatic analyses to gain a better understanding of risk factors for liver cancer.
Aims

1. To conduct a meta-analysis of genome-wide association studies for liver cancer
2. To genetic and bioinformatic analyses using genome-wide association study data (e.g. GxE and GxG interaction analyses, Mendelian randomization, heritability, mosaicism, gene- and pathway-based analyses, LD score regression and other bioinformatic analyses) to gain a better understanding of the etiology of liver cancer.

Collaborators

Karl Smith-Byrne (University of Oxford)