# Project 2: Integrating race, ethnicity, and genomic ancestry across GENIE to understand genetic and environmental contributions to pan-cancer risk, prognosis, and outcomes

> **NIH NIH P01** · SLOAN-KETTERING INST CAN RESEARCH · 2024 · $472,108

## Abstract

PROJECT 2 ABSTRACT
Integrating race, ethnicity, and genomic ancestry across GENIE to understand genetic and environmental
contributions to pan-cancer risk, prognosis, and outcomes.
Project Leaders: Ryan Hernandez (UCSF); Sasha Gusev (DFCI)
Despite significant advances in cancer biology and clinical oncology, race-based disparities in cancer outcomes
remain a long-standing challenge. Molecular mechanisms appear to play a role in some cancer disparities; a
notable example is the substantial excess of EGFR mutations in individuals of Asian ancestry with non-small cell
lung cancer. Racial differences have been identified in other cancers, including copy number alterations (CNAs)
that differ in frequency between African American and Caucasian women with triple negative breast cancer,
mutations in the EPHA6 and FLCN genes exclusive to African Americans with colorectal cancer, and recurrent
loss of function mutations in the ERF and KMT2D genes in African Americans with prostate cancer. Such exam-
ples have motivated the study of cross-population differences in cancer biology, especially in the context of
precision oncology. However, data from non-European individuals has been lacking, and most studies have
focused on a specific population or cancer type. Pan-cancer studies of genetic ancestry in The Cancer Genome
Atlas (TCGA) have identified ancestry-associated features across many cancer types, but have few individuals
from non-European populations, and only limited outcomes data from an outdated clinical context. The complex
relationship between race, genetic ancestry, somatic alterations, and clinical outcomes across cancers thus re-
mains largely unknown. The large-scale molecular profiling of tumors by AACR-GENIE presents an opportunity
to tackle these questions in thousands of non-European individuals with rich clinical outcomes in a contemporary,
real world clinical setting. The multi-institutional nature of GENIE also presents an opportunity to establish rigor-
ous methods and protocols for tumor-based ancestry inference across diverse platforms, and for analyses of
tumor-only somatic data from multi-ethnic populations. Finally, there is a history of biomedical research (including
cancer) focused on individuals of European ancestry. Such narrow focus has led to a deep understanding of the
role that select genes play in the etiology of various cancers but introduces bias into the selection of genes that
are interrogated with high throughput sequencing approaches. We will identify cancers for which there is a pau-
city of drivers among individuals with non-European ancestry compared to individuals with European ancestry.
We will utilize whole exome and RNA sequencing in diverse, driverless individuals to uncover new biology. In
collaboration with P01 co-investigators at AACR-GENIE institutions and our collaborators, these novel drivers will
be incorporated into future clinical sequencing panels.

## Key facts

- **NIH application ID:** 10768976
- **Project number:** 1P01CA275746-01A1
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Jian Zhang
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $472,108
- **Award type:** 1
- **Project period:** 2024-09-03 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10768976

## Citation

> US National Institutes of Health, RePORTER application 10768976, Project 2: Integrating race, ethnicity, and genomic ancestry across GENIE to understand genetic and environmental contributions to pan-cancer risk, prognosis, and outcomes (1P01CA275746-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10768976. Licensed CC0.

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