# Elucidating Lung Cancer Etiology Among Asian American Female Never Smokers

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $686,621

## Abstract

Abstract
Lung cancer in never smokers (LCINS) is a disease and disparity that disproportionately affects Asian American (AA)
females. In contrast to declining incidence trends seen among most racial/ethnic groups, incidence of lung cancer,
especially adenocarcinoma, has been increasing in most AA ethnic groups. The majority of AA females, upwards of
nearly 90% among Chinese, diagnosed with lung cancer have never smoked. There is very little known of the
contributing risk factors to the high and increasing incidence rates of LCINS among AA females, particularly as risk
factors identified in studies in Asia may have limited significance among AA populations. Moreover, there is limited
understanding of the relationships between the mutational signatures of tumors among this population and their
associated risk factors. Such information will improve our understanding of the underlying potential mechanistic
pathways. Thus, the overall objective of this study is to identify the attributable risk of known, putative, and suspected
risk factors for lung cancer among AA female never smokers. Recognizing that currently there are no U.S. datasets
nor existing cohorts with data for evaluating putative and suspected risk factors that may be most relevant to this
population, we propose a robust, population-based case-control study, leveraging early-case ascertainment methods
from cancer registries and tested state-of-the-science approaches for unbiased control ascertainment. With high-
quality, multilevel data collected from an estimated 600 female AA never-smoker lung cancer cases and 600
ethnicity and age frequency-matched controls, we aim to: Aim 1a. Identify risk factors for LCINS among AA females,
with attention to differences by histology and EGFR (epidermal growth factor receptor) status (determined using
whole exome sequencing [WES]), and focusing on multi-level factors including: a) genetic ancestry; b) individual-
level exposures, including putative and suspected risk factors; and c) contextual-level risk factors including indoor
and ambient air pollutants and the social environment, with consideration of nativity and years in the U.S. versus
Asia; Aim 1b. Determine the independent and joint contributions of multi-level risk factors to LCINS among AA
females by calculating the attributable risk for each risk factor, individually and in total; Aim 2a. Characterize the
mutational landscape of LCINS among AA females, through WES of paired tumor-normal tissue samples to define
somatic mutation profiles, mutational signatures, and EGFR status of LCINS AA females; and Aim 2b. Identify multi-
level risk factors associated with the major mutational tumor features. All aims will assess potential differences by
EGFR status. The proposed research will involve the assembly of the largest population-based lung cancer case-
control dataset, with associated genetic and tumor genomic data, for never-smoking AA women. It will provide a first-
ever opportunity to evalu...

## Key facts

- **NIH application ID:** 10093129
- **Project number:** 5R01MD014859-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Moon Shao-Chuang Chen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $686,621
- **Award type:** 5
- **Project period:** 2020-02-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10093129

## Citation

> US National Institutes of Health, RePORTER application 10093129, Elucidating Lung Cancer Etiology Among Asian American Female Never Smokers (5R01MD014859-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10093129. Licensed CC0.

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