title: 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).
  
  
  CONCLUSIONS
  Circulating levels of SP-D and KL-6 are associated with subsequent lung cancer risk.
  
  
  CONCLUSIONS
  Our findings support a potential role for interstitial lung disease in lung cancer etiology or early detection, but additional research is needed.
authors.affiliation: Infections and Immunoepidemiology Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20852, USA. shielsms@mail.nih.gov
authors.forename: Meredith S
authors.initials: MS
authors.lastname: Shiels
authors.forename: Anil K
authors.initials: AK
authors.lastname: Chaturvedi
authors.forename: Hormuzd A
authors.initials: HA
authors.lastname: Katki
authors.forename: Bernadette R
authors.initials: BR
authors.lastname: Gochuico
authors.forename: Neil E
authors.initials: NE
authors.lastname: Caporaso
authors.forename: Eric A
authors.initials: EA
authors.lastname: Engels
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D018287:Carcinoma, Large Cell / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017563:Lung Diseases, Interstitial / Q000097:blood / Q000150:complications*; D008175:Lung Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000097:blood; D011379:Prognosis; D037663:Pulmonary Surfactant-Associated Protein D / Q000097:blood; D013902:Radiography, Thoracic; D012307:Risk Factors; D055752:Small Cell Lung Carcinoma / Q000097:blood / Q000175:diagnosis* / Q000209:etiology
chemical_list: D014408:Biomarkers, Tumor; C060192:MUC1 protein, human; D018396:Mucin-1; D037663:Pulmonary Surfactant-Associated Protein D