Infections and Immunoepidemiology Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20852, USA.
Cancer Epidemiol Biomarkers Prev. 2011 Oct;20(10):2262-72. doi: 10.1158/1055-9965.EPI-11-0326. Epub 2011 Aug 9.
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.
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.
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).
Circulating levels of SP-D and KL-6 are associated with subsequent lung cancer risk.
Our findings support a potential role for interstitial lung disease in lung cancer etiology or early detection, but additional research is needed.
炎症和肺部疾病（包括间质性肺疾病）与肺癌风险增加有关。表面活性蛋白-D（SP-D）和 Krebs von Lungren-6（KL-6）在间质性肺疾病患者中的循环水平升高，可能是导致肺癌的相关过程的有用标志物。
我们在前列腺癌、肺癌、结直肠癌和卵巢癌筛查试验中进行了一项巢式病例对照研究，纳入了 532 例肺癌病例、582 例匹配对照和 150 例胸部 X 线（CXR）有肺部瘢痕证据的对照。使用酶联免疫吸附试验测量血清 SP-D 和 KL-6 水平。使用逻辑回归估计 SP-D 和 KL-6 与肺癌和 CXR 瘢痕的关联。
与对照组相比，病例组的 SP-D（中位数 118.7 比 105.4ng/ml，P = 0.008）和 KL-6（372.0 比 325.8μg/ml，P = 0.001）水平更高。肺癌风险随着 SP-D（P（趋势）= 0.0003）和 KL-6 水平的增加而增加（P（趋势）= 0.005）。与最低四分位数相比，SP-D 最高四分位数（OR = 1.87，95%CI：1.32-2.64）或 KL-6（OR = 1.58，95%CI：1.11-2.25）的肺癌风险升高。在对照组中，与无瘢痕的参与者相比，有 CXR 瘢痕的参与者更有可能具有较高水平的 SP-D（四分位数 4 比四分位数 1：OR = 1.67，95%CI：1.04-2.70，P（趋势）= 0.05），但 KL-6 水平无差异（OR = 1.04，95%CI：0.64-1.68，P（趋势）= 0.99）。
循环 SP-D 和 KL-6 水平与随后的肺癌风险相关。
我们的发现支持间质性肺疾病在肺癌病因学或早期检测中的潜在作用，但需要进一步的研究。
