Abstract 2920: Circulating inflammation markers and subsequent lung cancer risk: A discovery and replication study
Authors: Shiels Meredith S. , Katki Hormuzd A. , Hildesheim Allan , Pfeiffer Ruth M. , Engels Eric A. , Williams Marcus C. , Kemp Troy J. , Caporaso Neil E. , Pinto Ligia A. , Chaturvedi Anil K. 
Published: May 2015

Background: Few epidemiologic studies have investigated the role of inflammation in lung cancer etiology. We have carried out 2 independent studies nested within the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial to assess associations between circulating inflammation markers and lung cancer risk, after carefully controlling for smoking. In the discovery study, we showed associations between 11 circulating inflammation markers (CRP, SAA, sTNFRII, IL-1RA, IL-7, TGF-A, ENA 78/CXCL5, MIG/CXCL9, BCA-1/CXCL13, TARC/CCL17 and MDC/CCL22) and prospective lung cancer risk (Shiels, JNCI 2013). To assess the reproducibility of these associations, we have carried out a large, independent replication study.

Methods: We designed a replication case-control study nested within the PLCO in 526 lung cancer cases and 625 controls, matched by gender, age, smoking (status, pack-years and time since quit), study visit and years of blood draw and exit. Serum levels of 51 inflammation markers were measured using Luminex bead-based assays. We combined the data from the discovery and replication studies (1052 cases and 1217 controls) and created study-specific marker categories. Conditional logistic regression was used to estimate odds ratios (ORs) overall and stratified by latency and histology in the pooled dataset.

Results: In our prior study, 11 inflammation markers were associated with lung cancer risk with ORs ranging from 1.41 to 2.27. Of these 11 markers, C-reactive protein (CRP), serum amyloid A (SAA), soluble tumor necrosis factor receptor 2 (sTNFRII) and monokine induced by gamma interferon (MIG/CXCL9) were associated with prospective lung cancer risk in the replication study with ORs ranging from 1.70 to 2.09 (p-trend across quartiles3 years) (all p-interactions&gt;0.2). Further, each marker was associated with both lung adenocarcinoma and squamous cell carcinoma (all p-trends&lt;0.05).

Conclusions: With results from two independent case-control studies, we have confirmed that pre-diagnostic circulating levels of two acute phase proteins (CRP and SAA), a receptor for a pro-inflammatory cytokine (sTNFRII), and a chemokine (MIG/CXCL9) are each associated with prospective lung cancer risk, after carefully controlling for cigarette smoking. These results provide evidence implicating inflammation in the development of lung cancer.

Citation Format: Meredith S. Shiels, Hormuzd A. Katki, Allan Hildesheim, Ruth M. Pfeiffer, Eric A. Engels, Marcus C. Williams, Troy J. Kemp, Neil E. Caporaso, Ligia A. Pinto, Anil K. Chaturvedi. Circulating inflammation markers and subsequent lung cancer risk: A discovery and replication study. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2920. doi:10.1158/1538-7445.AM2014-2920