FULL PROJECT 1 - Circulating Immune Cell Profiles, Immune Biomarkers and Lung Cancer Risk

Lung cancer is the leading cause of cancer death in the U.S., with African Americans (AAs) suffering a higher incidence than any other population group, which cannot be fully accounted for by smoking and other known risk factors. It is well-recognized that the immune system, including peripheral blood leukocytes, plays a key role in protecting hosts against cancers. However, direct evidence linking pre-diagnostic circulating immune cell profiles with lung cancer risk is limited. Recently, we conducted a pilot study, using a novel robust and reliable genomics-based approach, and found that circulating immune cell profiles differed between AAs and European Americans (EAs), and between smokers and non-smokers. Several circulating pro- or anti-inflammatory cytokines have been reported to be associated with lung cancer risk. However, most prior studies only investigated a few candidate immune biomarkers and the results are not consistent. In our recently conducted pilot studies, we found that genetically predicted plasma cytokine levels were associated with lung cancer risk. These findings provide a strong scientific premise for the proposed project and support our hypotheses that circulating immune cell profiles and immune biomarkers are associated with subsequent lung cancer risk, and differences in immune cell profiles and biomarkers between AA and EA may explain, at least in part, the differences lung cancer incidence. To test these novel hypotheses, we propose to conduct nested case-control study using the exceptional resources from the Southern Community Cohort Study (SCCS), a prospective cohort study of ~86,000 adults, two-thirds AAs, and the remainder mostly non-Hispanic EAs. In Aim 1, we will investigate immune cell profiles in pre-diagnostic blood samples from 800 cases and their individually matched controls in association with lung cancer risk. Statistical analyses will be conducted separately for AAs and EAs to directly compare the association of immune cell profiles with lung cancer risk between these two populations. Project Number: 5U54CA163066-15 | Fiscal Year: 2025 | NIH Institute/Center: National Cancer Institute (NCI) | Principal Investigator: MARGARET WHALEN (+1 co-PI) | Institution: TENNESSEE STATE UNIVERSITY, NASHVILLE, TN | Award Amount: $112,808 | Activity Code: U54 | Study Section: ZCA1-SRB-2(A1)S View on NIH RePORTER: https://reporter.nih.gov/project-details/11397673