Circulating markers of interstitial lung disease and subsequent risk of lung cancer.

Abstract

BACKGROUND:

Inflammation and pulmonary diseases, including interstitial lung diseases, are associated with increased lung cancer risk. Circulating levels of surfactant protein-D (SP-D) and Krebs von Lungren-6 (KL-6) are elevated in interstitial lung disease patients and may be useful markers of processes contributing to lung cancer.

METHODS:

We conducted a nested case-control study, including 532 lung cancer cases, 582 matched controls, and 150 additional controls with chest X-ray (CXR) evidence of pulmonary scarring, in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Serum SP-D and KL-6 levels were measured using enzyme immunoassay. Logistic regression was used to estimate the associations of SP-D and KL-6 with lung cancer and CXR scarring.

RESULTS:

Cases had higher levels than controls for SP-D (median 118.7 vs. 105.4 ng/mL, P = 0.008) and KL-6 (372.0 vs. 325.8 μg/mL, P = 0.001). Lung cancer risk increased with SP-D (P(trend) = 0.0003) and KL-6 levels (P(trend) = 0.005). Compared with the lowest quartile, lung cancer risk was elevated among those with the highest quartiles of SP-D (OR = 1.87, 95% CI: 1.32-2.64) or KL-6 (OR = 1.58, 95% CI: 1.11-2.25). Among controls, participants with CXR scarring were more likely than those without scarring to have elevated levels of SP-D (quartile 4 vs. quartile 1: OR = 1.67, 95% CI: 1.04-2.70, P(trend) = 0.05) but not of KL-6 (OR = 1.04, 95% CI: 0.64-1.68, P(trend) = 0.99).

CONCLUSION:

Circulating levels of SP-D and KL-6 are associated with subsequent lung cancer risk.

IMPACT:

Our findings support a potential role for interstitial lung disease in lung cancer etiology or early detection, but additional research is needed.

• Authors: Meredith S Shiels, Anil K Chaturvedi, Hormuzd A Katki, Bernadette R Gochuico, Neil E Caporaso, Eric A Engels
• Journal: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology (Cancer Epidemiol Biomarkers Prev) Vol. 20 Issue 10 Pg. 2262-72 (Oct 2011) ISSN: 1538-7755 [Electronic] United States
• PMID: 21828236 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)
• Copyright: ©2011 AACR

Chemical References

• Biomarkers, Tumor
• MUC1 protein, human
• Mucin-1
• Pulmonary Surfactant-Associated Protein D

Topics

• Adenocarcinoma (blood, diagnosis, etiology)
• Aged
• Biomarkers, Tumor (blood)
• Carcinoma, Large Cell (blood, diagnosis, etiology)
• Carcinoma, Squamous Cell (blood, diagnosis, etiology)
• Case-Control Studies
• Female
• Follow-Up Studies
• Humans
• Lung Diseases, Interstitial (blood, complications)
• Lung Neoplasms (blood, diagnosis, etiology)
• Male
• Middle Aged
• Mucin-1 (blood)
• Prognosis
• Pulmonary Surfactant-Associated Protein D (blood)
• Radiography, Thoracic
• Risk Factors
• Small Cell Lung Carcinoma (blood, diagnosis, etiology)