Meredith Shiels

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NCI

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PLCO (Learn more about this study)

2012-0356

Oct 22, 2012

Circulating inflammation markers and risk of lung cancer: A replication study

Both experimental and epidemiologic studies support a role for chronic inflammation in lung carcinogenesis. We have conducted several studies within the PLCO screening arm to investigate the role of chronic inflammation in the etiology of lung cancer. Building on these promising findings for an etiologic role for chronic inflammation in lung carcinogenesis, we recently conducted a comprehensive evaluation of the association of circulating levels of 77 inflammation markers with incident lung cancer risk in a nested case-control study within the PLCO trial. We found that 11 markers were significantly associated with lung cancer risk (BCA-1, CRP, CXCL9 MIG, ENA 78, IL-1RA, IL-7, MDC, SAA, STNFRII, SVEGFR2, and TARC), with an odds ratio of 0.71 for IL-1RA and odds ratios (comparing the highest category with the lowest) ranging from 1.47-2.33 for the remaining markers. Additionally, 7 other markers (TGF-A, IL-1B, GRO, TNF-B, SAP, STNFR1, and IL-10) were found to have marginal associations with lung cancer. Importantly, the markers associated with lung cancer encompass the spectrum of carcinogenesisinnate and adaptive immune activation, angiogenesis, and tumorigenesisunderscoring an etiologic role for chronic inflammation in lung cancer. Our recently completed study is the most comprehensive assessment to date of the association between circulating levels of inflammation markers and lung cancer risk. Although our findings are promising, like with any new technology that seeks to assess a number of markers simultaneously, our results need to be replicated in an independent sample to rule out the possibility of false-positive associations. Therefore, to replicate our findings, we propose to conduct a nested case-control study within the screening arm of the PLCO trial, excluding the cases already tested in our prior study. We propose to select 526 lung cancers and 600 controls; controls will be matched to cases on age at randomization, sex, year of randomization, length of follow-up during the study, smoking status, pack-years smoked for current and former smokers, and time since quitting for former smokers. Inflammation markers will be measured in 420 uL of serum using Millipores multiplexed bead-based assays. We will evaluate the association between each marker and lung cancer risk in the proposed study to replicate our ongoing study, and then will combine data from both studies to provide more precise estimates for each marker.