African Americans have a higher risk of developing lung cancer compared with all other ethnic groups in the USA. Previous studies based on a small panel of markers suggested that certain circulating cytokines were associated with lung cancer. Given the complexity of the immune response in lung cancer and the multitude of cell types involved, we reasoned that examining a broad panel of inflammatory markers—including cytokines, chemokines, angiogenic and other pro-inflammatory factors—might identify a diagnostic signature of lung cancer for African American patients.
Differences in 30 inflammatory marker serum levels were measured in 316 African-American cases and 508 African American controls from the National Cancer Institute-Maryland (NCI-MD) case-control study using a Mesoscale (MSD) multiplex platform. The panel of 30 serum inflammatory markers included chemokines, cytokines and other inflammatory related proteins. Logistic regression analyses were conducted to investigate the association between levels of inflammatory marker expression and lung cancer risk. Expression levels above the median threshold defined within the control samples were considered high. Statistical models were also adjusted for potential confounding factors such as age, gender, pack-years and smoking status.
Nineteen inflammatory markers (CRP, IFN-ϒ, IL-10, IL-15, IL-17A, IL-1α, IL-1β, IL-4, IL-5, IL-6, IL-7, IL-8, IP-10, MCP-4, MIP-1α, TARC, TNF-α, TNF-β and VEGF) were significantly different among African American cases compared with African American controls (P<0.05). In agreement with our previous observations, levels of IL-10, IL-1β, IL-6, IL-8, and TNF-α were associated with lung cancer risk. In addition, we found that CRP, IFN-ϒ, IL-15, IL-7, IP-10, MCP-4, MIP-1 α, TARC, TNF-β and VEGF were associated with lung cancer in African Americans. The associations between CRP, IFN-ϒ, IL-10, IL-15, IL-1β, IL-5, IL-6, IL-7, IL-8, IP-10, MCP-4, MDC, MIP-1α, TNF-α and TNF-β levels and lung cancer among African Americans was significant after adjustment for additional potential confounding factors.
Serum cytokine levels vary by race and might contribute to lung cancer differently in African Americans and European Americans. The findings presented here build upon recent work that identified associations between elevated levels of IL-10, IL-1β, IL-6, IL-8, TNF-α and lung cancer specifically among African Americans. By analyzing a broader spectrum of inflammatory measures, we have identified additional markers of lung cancer for African American patients. Further to this, we have integrated GWAS and MSD data for 137 cases and 203 controls that allows us to examine the genetic basis to the relationship between risk of lung cancer and modulated inflammatory marker expression. Markers identified here as significant for lung cancer risk will be further analyzed using case-control samples from an independent African American validation cohort.
Citation Format: Claire L. Meaney, Khadijah A. Mitchell, Adriana Zingone, Derek Brown, Wei Tang, Yunkai Yu, Liang Cao, Angela S. Wenzlaff, Ann G. Schwartz, Brid M. Ryan. Inflammatory based diagnostic markers of lung cancer in African Americans [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4658. doi:10.1158/1538-7445.AM2017-4658