Background: It is unclear why poor Americans die of non-small cell lung cancer (NSCLC) at a significantly higher rate than their affluent counterparts. We aimed to evaluate the relationship between (1) social determinants of health (SDH) (e.g., pollution, education), (2) cigarette smoke, and (3) aggressive NSCLC somatic biologic phenotypes (e.g., KRAS G12C and G12V and TP53 mutations) in smoking and nonsmoking patients with NSCLC. We hypothesize that adverse social determinants will be associated with more aggressive NSCLC tumor biology.

Methods: We conducted a single institutional retrospective cohort study of patients seen at the City of Hope National Medical Center from 2015-2018. Clinical data were obtained from electronic medical records. Risk factor data (air quality measure [PM 2.5 exposure], neighborhood-level income, education, and minority population data) were obtained from the Environmental Protection Agency (EPA). Associations were modeled using logistic regression models, controlling for all demographic variable (TP53) or variables significant on bivariate analyses (KRAS variants G12C and G12V).

Results: Of 812 NSCLC patients, 617 (76%) had somatic genomic testing and were included in analyses (mean age 67.6, 53% female, 30% Asian, 4% African American, 64% White, 10% Hispanic, 64.3 % Stage 4, 83% adenocarcinoma, and 38% never smokers). Smokers had a mean pack-year of 20. 22% of patients had KRAS mutations and 42.6% had TP53 mutations. For neighborhood level exposures, the mean PM 2.5 level was 11.7 μg/m3 (US average is 9.5 μg/m3). Patients were almost evenly distributed in the good and moderate PM2.5 risk categories (good 47.6%, moderate 52.4%). There was no overall association between SDH and KRAS mutations. However, multivariable analyses revealed that lower neighborhood education (OR=15.98, 95%CI 1.5-170.4) was associated with KRAS variants G12C and G12V specifically. Poor air quality as measured by PM2.5 was associated with TP53 mutations (OR=2.09, 95%CI 1.33-3.29).

Conclusion: Poor air quality is associated with increased risk of TP53 mutations, while low neighborhood-level education is associated with KRAS G12C/G12V mutations. Our study finds a link between adverse neighborhood-level social determinants and aggressive biologic NSCLC behavior. These hypothesis-generating findings suggest a mechanism by which deprived NSCLC populations may experience inferior outcomes. Larger, prospective studies are needed to further evaluate these associations.

This abstract is also being presented as Poster C054.

Citation Format: Loretta Erhunmwunsee, Hengrui Hu, Catherine Raquel, Lisa N. Lopez, Jenny Shen, Lennie Wong, Jae Y. Kim, Dan J. Raz, Karen L. Reckamp, Ravi Salgia, Stacy W. Gray. Neighborhood-level social determinants impact non-small cell lung cancer aggressive somatic phenotypes [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr PR08.