# Project 1: Smoking, environmental and genomic factors in lung cancer and managing risk

> **NIH NIH U19** · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · 2024 · $939,270

## Abstract

Project Summary/Abstract
Lung cancer (LC) is a “poster child” for a disease resulting from interactions between genetic and environmental risk
factors. Ongoing LC genome wide association studies (GWAS) conducted by us have identified over 40 loci involved
in LC susceptibility that have dramatically improved the understanding of the genetic architecture of LC risk. However,
there is a significant bias in the conducted GWASs: most studies have involved populations of European descent.
Ancestry plays an important role in LC risk through contribution of ancestry- specific germline polymorphisms as well
as socio-cultural differences including environmental exposures. We hypothesize that a “one size (ancestry) fits
all” model is not applicable to LC and that exploring risk of LC and its translation across ancestries manner
will improve the understanding of LC risk and prevention in diverse human populations. Our specific aims
include the following. Aim 1. To precisely characterize the contribution of genetic variation to lung cancer
etiology. The genetic approach will include genotyping arrays and low pass whole genome sequencing (WGS) and
imputation into the large multi-ethnic reference panels to generate the world largest resource for the discovery of lung
cancer susceptibility variants influencing lung cancer risk across a range of ethnicities. Aim 2. To perform post-
GWAS analysis to identify environmental and host-specific factors influencing lung cancer development.
Mendelian randomization will enable the identification of causal molecular factors, such as biomarkers,
influencing lung cancer, which facilitates developing screening programs for lung cancer (Projects 2 and 3. In
addition, we will also use forward and reverse Mendelian randomization to partition the causal effects of
biomarkers on lung cancer risk according to cis-acting genetic components, trans-acting components related to
broader host-exposures and external factors. We will develop and use novel annotation methods to identify most
likely causal variants to improve polygenic risk score development. Aim 3. To develop population-specific as
well as multi-ancestry polygenic risk scores (PRSs) to refine risk estimation of LC for minority
populations. In this aim, we will first build and characterize PRSs from genomic analyses to identify subsets of
individuals at high risk for lung cancer development1. Second, to date, studies have focused on analysis in
European-descent populations. Aim 4. To evaluate the impact of returning genetic risk factors information
to motivate behavior change in diverse populations and to scrutinize direct translational implications of
the genomic findings from our ancestry-specific and cross-ancestry studies. In this translational aim, we
will engage both patients and healthcare providers by adopting a rapid cycle research approach to reduce the
time lag from discovery to practice while accommodating evolving genomic evidence base. This project provides
dat...

## Key facts

- **NIH application ID:** 11295079
- **Project number:** 7U19CA203654-09
- **Recipient organization:** UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
- **Principal Investigator:** Christopher I. Amos
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $939,270
- **Award type:** 7
- **Project period:** 2017-08-01 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11295079

## Citation

> US National Institutes of Health, RePORTER application 11295079, Project 1: Smoking, environmental and genomic factors in lung cancer and managing risk (7U19CA203654-09). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11295079. Licensed CC0.

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