Circulating Inflammation Markers Associated With Risk of Lung Cancer

Key Points

  • Eleven circulating inflammation markers were significantly associated with risk of lung cancer.
  • An inflammation risk score based on four markers distinguished risk levels among former and current smokers after adjustment for smoking exposure.

In a study reported in the Journal of the National Cancer Institute, Shiels et al identified 11 circulating inflammation markers significantly associated with lung cancer risk. A risk score using four of the markers distinguished risk levels among current and former smokers.

Study Details

This nested case-control study involved 526 patients with lung cancer and 592 control subjects from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial matched for age, sex, follow-up time, randomization year, and smoking (pack-years and time since quitting). Lung cancer screening in this trial included collection of blood samples at baseline and at five subsequent annual visits.

Serum levels of 77 circulating inflammation markers were measured with a Luminex bead-based assay. Case patients were significantly more likely to have lower education, history of bronchitis/emphysema, and family history of lung cancer. The median time from serum collection to lung cancer diagnosis or selection as control subject was 2.9 years.

Markers Associated With Risk

In total, 11 markers were significantly associated with lung cancer risk in conditional logistic regression models adjusting for matching criteria, history of bronchitis/emphysema, history of coronary heart disease or heart attack, family history of lung cancer, use of aspirin/ibuprofen, body mass index, race, and education. The markers  consisted of the acute-phase proteins C-reactive protein (CRP) and serum amyloid A (SAA), the proinflammatory cytokine soluble tumor necrosis factor receptor 2 (sTNFRII), the anti-inflammatory cytokine interleukin 1 receptor antagonist (IL-1RA), the lymphoid differentiation cytokine IL-7, the growth factor transforming growth factor alpha (TGF-A), and the chemokines epithelial neutrophil-activating peptide 78 (ENA 78/CXCL5), monokine induced by gamma interferon (MIG/CXCL9), B cell-attracting chemokine 1 (BCA-1/CXCL13), thymus activation regulated chemokine (TARC/CCL17), and  macrophage-derived chemokine (MDC/CCL22).

Odds ratios (ORs) for lung cancer associated with elevated marker levels (highest vs lowest levels) ranged from 1.47 for IL-7 to 2.27 for CRP; elevated IL-1RA levels were associated with reduced risk with an odds ratio of 0.71. No significant difference in the associations were observed according to latency, histology, or smoking, except for differences according to smoking for IL-1RA and to histology for TGF-A.

Inflammation Score

Of the 11 markers, CRP, BCA-1/CXCL-13, MDC/CCL22, and IL-1RA remained significant in backward stepwise regression analysis. An inflammation score based on these four markers was associated with a 2.8-fold increased risk of lung cancer between the lowest and highest risk score quartiles (OR = 2.79, P < .001 for trend). From the lowest to highest quartiles, 10-year cumulative risk increased from 1.1% to 3.1% in former smokers and from 2.3% to 7.9% in current smokers after adjustment for smoking exposure.

The investigators concluded: "[O]ur study extends observations from laboratory studies and single-marker association studies by providing epidemiologic evidence for the association of acute-phase proteins, pro- and anti-inflammatory cytokines, chemokines, and growth factors with prospective lung cancer risk. The separation in lung cancer cumulative risks across the inflammation score among current and former smokers provides preliminary evidence for the potential utility of inflammation markers in lung cancer risk stratification.”

Meredith S. Shiels, PhD, of the National Cancer Institute, is the corresponding author for the Journal of the National Cancer Institute article.

The study was supported by the National Cancer Institute.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.