# Hereditary Genetics of Hepatocellular Carcinoma

> **NIH NIH R37** · MAYO CLINIC ROCHESTER · 2022 · $510,314

## Abstract

PROJECT SUMMARY
Hepatocellular Carcinoma (HCC) is a devastating and prevalent cancer of the liver with high rates of mortality.
Major risk factors include chronic viral infection (hepatitis B or C), fatty liver disease, alcohol use, and exposure
to environmental toxins. An independent risk factor is a family history of HCC in a first degree relative, which
raises the risk by more than 2.5-fold. However, despite evidence of familial risk, few links to hereditary cancer
syndromes have been identified. It is also not clear whether inherited gene mutations play a pathogenic role in
HCC development, or whether they could be used to guide treatment. We have pioneered an investigation into
inherited (i.e. germline) genetic factors associated with HCC. We have prospectively enrolled 220 patients with
HCC from our medical center for clinical-grade genetic testing. We have recorded the details of their personal
and family cancer history, risk factors, and outcomes. In our pilot analysis, we found a surprisingly high rate of
pathogenic germline mutations in cancer-associated genes in patients with HCC, including numerous mutations
in DNA damage response genes required for homologous repair (HR-DDR). In Aim 1, we will conduct a genetic
association study that is powered to detect clinically meaningful germline mutations linked to HCC, and we will
examine whether hereditary cancer syndromes are more common in persons who developed early onset HCC
or have a family history of cancer. In Aim 2, we will explore the mechanism of HCC arising from defects in HR-
DDR genes, and determine the implications for targeted therapies. These unique studies of the hereditary
genetics of HCC have the potential to personalize therapies for the subset of patients with hereditary cancer
syndromes. We have assembled a team of experts in HCC, hereditary genetics, and animal models to complete
this investigation. This study has the potential to shape the care of patients with HCC in the US and worldwide.

## Key facts

- **NIH application ID:** 10632953
- **Project number:** 7R37CA259201-02
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Kirk J Wangensteen
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $510,314
- **Award type:** 7
- **Project period:** 2022-07-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10632953

## Citation

> US National Institutes of Health, RePORTER application 10632953, Hereditary Genetics of Hepatocellular Carcinoma (7R37CA259201-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10632953. Licensed CC0.

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