Grant Number:	5R01CA262540-04 Interpret this number
Primary Investigator:	Cheng, Iona
Organization:	University Of California, San Francisco
Project Title:	Understanding the Role of Area-Level Factors, Smoking, and Epigenetics in Lung Cancer Risk Across Populations Groups
Fiscal Year:	2025

Despite the overall progress in the U.S. in lowering the prevalence of cigarette smoking and lung cancer incidence rates, the persistent differences in the burden of lung cancer across population groups is a major public health problem. Over decades, African American and Native Hawaiian adults have suffered a disproportionate incidence of lung cancer in comparison to other population groups. The concerning observation that African American and Native Hawaiian adults experience a higher risk, compared to Japanese American, Latino, and White adults, for the same lifetime exposure to smoking has fueled studies to investigate differences in genetic susceptibility, biomarkers of smoking, and epigenetics. While these studies have shed light on the contribution of molecular factors to differences in lung cancer risk, both molecular, genetic and individual-level lifestyle factors are unable to account fully for these population differences in lung cancer risk. Thus, there is a clear need to address how area-level factors such as housing, poverty, tobacco retail outlets, and access to health care influence lung cancer risk across population groups. To address this gap, we will leverage the unique epidemiological resources of the Multiethnic Cohort Study and Southern Community Cohort Study. These two large cohorts include over 272,000 well-characterized adult participants with up to 27 years of follow-up and high-quality cancer surveillance data. Specifically, we will assess the impact of area-level factors on: change in smoking status and internal smoking dose (Aim 1); lung cancer risk across population groups (Aim 2); and DNA methylation in blood leukocytes (Aim 3). In addition, we will evaluate whether known risk factors for lung cancer mediates the relationships between area-level factors and lung cancer risk. We will also assess whether DNA methylated sites and epigenetic age mediate the associations between area-level factors and lung cancer risk (Aim 3). The strengths of this proposal include: 1) the integration of two population-based cohorts, statistically powered to study five population groups from urban and rural settings, ensuring high-risk populations will be studied; 2) the public health significance of understanding risk factors that influence population differences in smoking behaviors and lung cancer risk; 3) the assessment of the biological pathways by which area-level factors lead to lung cancer risk. Findings from this proposal will expand our understanding of the contribution of risk factors to lung cancer development and the underlying biological pathways by which they may operate. This knowledge has translational relevance in providing empirical evidence to support the development of interventions for smoking and lung cancer risk that may have broad health benefits for other chronic diseases.




[¹⁸F]-FLT-PET to evaluate how the sequencing of chemotherapies impacts the efficacy of combination treatment in mouse models of triple-negative breast cancer.
Authors: Lu Y. , Moye J. , Massicano A.V.F. , Gallegos C.A. , Lynch S.E. , Song P.N. , Samuel S. , Sorace A.G. .
Source: Neoplasia (new York, N.y.), 2025 Aug; 66, p. 101184.
EPub date: 2025-05-27 00:00:00.0.
PMID: 40424979
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