<p>Supplemental Table 4. Frequency of DNA hypermethylation of markers in subjects with</p><p>(n=361) and without (n=58) COPD stratified for lung cancer or control for a) statistical approach i, and b) statistical approach ii. Subjects of both learning and validation sets were combined. P-values are calculated with chi-square tests to assess the difference in </p><p>DNA hypermethylation between both groups.</p><p> a) Statistical approach i</p><p>Marker Lung cancer Controls</p><p> no COPD COPD p-value no COPD COPD p-value</p><p> n/42 % n/147 % n/16 % n/214 %</p><p>RASSF1A 16 38.1% 53 36.1% 0.81 1 6.3% 19 8.9% 1.00*</p><p>APC 19 45.2% 77 52.4% 0.41 4 25.0% 65 30.4% 0.78*</p><p>CYGB 22 52.4% 78 53.1% 0.94 4 25.0% 63 29.4% 1.00*</p><p>3OST2 21 50.0% 72 49.0% 0.91 3 18.8% 28 13.1% 0.46*</p><p>PRDM14 29 69.0% 91 61.9% 0.40 4 25.0% 51 23.8% 1.00*</p><p>FAM19A4 32 76.2% 120 81.6% 0.43 11 68.8% 161 75.2% 0.56*</p><p>PHACTR3 26 61.9% 85 57.8% 0.64 8 50.0% 65 30.4% 0.10</p><p>* p-value based on Fisher’s exact test</p><p> b) Statistical approach ii</p><p>Marker Lung cancer Control</p><p> no COPD COPD p-value no COPD COPD p-value</p><p> n/42 % n/14 % n/16 % n/21 %</p><p>7 4</p><p>1 RASSF1A 16 38.1% 53 36.1% 0.81 1 6.3% 19 8.9% 1.00*</p><p>APC 8 19.0% 30 20.4% 0.85 0 0% 8 3.7% 1.00*</p><p>CYGB 8 19.0% 27 18.4% 0.92 0 0% 6 2.8% 1.00*</p><p>3OST2 15 35.7% 46 31.3% 0.59 0 0% 7 3.3% 1.00*</p><p>PRDM14 10 23.8% 35 23.8% 1.00 2 12.5% 5 2.3% 0.078*</p><p>FAM19A4 12 28.6% 30 20.4% 0.26 2 12.5% 5 2.3% 0.078*</p><p>PHACTR3 13 31.0% 36 24.5% 0.40 2 12.5% 13 6.1% 0.32*</p><p>* p-value based on Fisher’s exact test</p><p>2</p>