Grant Number:	5R01CA262540-02 Interpret this number
Primary Investigator:	Cheng, Iona
Organization:	University Of California, San Francisco
Project Title:	Understanding the Role of Structural Racism on Racial/Ethnic Inequities in Lung Cancer Risk
Fiscal Year:	2023

ABSTRACT Despite the overall progress in lowering the prevalence of cigarette smoking and incidence rates of lung cancer in the U.S., the persistent racial/ethnic and socioeconomic (SES) inequities in the burden of lung cancer are major public health problems. Over decades, African Americans and Native Hawaiians have suffered a disproportionate incidence of lung cancer in comparison to other racial/ethnic groups. The concerning observation that African Americans and Native Hawaiians experience a higher risk of lung cancer, compared to European, Japanese, and Latin Americans, for the same lifetime exposure to smoking has fueled molecular epidemiology studies of smoking and lung cancer to investigate racial/ethnic differences in genetic susceptibility, biomarkers of smoking, and epigenetics. While these studies have shed light on the contribution of molecular factors to racial/ethnic differences in lung cancer risk, both molecular, genetic and individual-level lifestyle factors are unable to account fully for the racial/ethnic differences in lung cancer risk. Thus, there is a clear need to address how upstream factors of social determinants of health, including structural racism, influence lung cancer inequities. 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 structural racism and neighborhood disinvestment on: change in smoking status and internal smoking dose (Aim 1); racial/ethnic and SES inequities in lung cancer risk (Aim 2); and DNA methylation in blood leukocytes (Aim 3). In addition, we will evaluate whether air pollution mediates the relationships between structural racism and lung cancer inequities. We will also assess whether DNA methylated sites and epigenetic age mediate the association between structural racism 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 racial/ethnic groups from urban and rural settings, ensuring the representation of understudied high-risk populations; 2) the public health significance of addressing the influence of structural racism on smoking and lung cancer inequities; 3) the assessment of the biological pathways by which structural racism is embodied and leads to lung cancer inequities. Findings from this proposal will expand our understanding of the contribution of structural racism to lung cancer development and the underlying biological pathways by which structural racism may operate. This knowledge has translational relevance in providing empirical evidence for community stakeholders, policy makers, and implementation scientists to develop interventions for smoking and lung cancer that also may have broad health benefits.





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