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Lung cancer in never smokers: incidence, risk factors, and molecular characteristics in Asian American, Native Hawaiian and Pacific Islanderfemales

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? DESCRIPTION (provided by applicant): For females of Asian Americans, Native Hawaiians and Pacific Islanders (AANHPI) ethnic groups, lung cancer is the 3rd or 4th most common cancer, but the most common cause of cancer death. The burden of lung cancer among AANHPI females is striking considering their low prevalence of smoking, that more than half of lung cancers occur in never smokers, and contributing risk factors beyond smoking remain largely unknown. Furthermore, the incidence rates of lung cancer, especially adenocarcinoma, are either stable or increasing among Filipina, Korean, and Chinese American females, in stark contrast to the overall declining incidence rates of lung cancer in other U.S. racial/ethnic groups Given the lack of information on smoking status for populations at risk, population-level incidence rates stratified by smoking status, race/ethnicity, and sex are not available, constituting a critical gap in knowledge. At present, there is no single sufficiently large data source to document lung cancer incidence rates by smoking status among specific AANHPI ethnic groups, which is central to understanding and reducing the burden of disease in this heterogeneous population that includes individuals from more than 30 different countries, speaking more than 100 languages. To address these gaps, the objective of our study is to leverage prospective data from two large electronic health record (EHR) databases, comprising 3.2 million individuals, 1.8 million females, and over 240,000 AANHPI females, with up to 15 years follow-up, to estimate their lung cancer incidence and characterize the epidemiology of lung cancer by specific single and mixed race/ethnicity and smoking status. For Aim 1, we will calculate overall and histological cell-type specific incidence rates of lung cancer by smoking status, and compare the distribution of sociodemographic, tumor (e.g. stage, histology), and molecular characteristics (e.g. EGFR, ALK) of lung cancer cases by race/ethnicity and smoking status. Males and other races/ethnicities will be examined for comparison in Aim 1. For Aim 2, we will conduct a longitudinal analysis of lung cancer risk, including absolute risk modeling, examining six exposure domains: second-hand smoke, previous lung diseases, infections, reproductive history and hormone exposure, body size, and neighborhood environmental factors, including measures of particulate matter, traffic density, neighborhood socioeconomic status, and ethnic enclave. This study will use EHR data from the Northern California Sutter Health system and from Kaiser Permanente Hawaii - each specifically selected for their robust AANHPI representation and high quality data. Coupled with a focus on distinct subpopulations defined by race/ethnicity (including well-defined mixed race/ethnic groups), smoking status, environmental characteristics, and tumor-based molecular markers, this highly efficient study will provide much-needed information on lung cancer risk among AANHPI never smokers, serving as a critical evidence base to inform screening, research, and public health priorities in this growing population.
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