1.89 0.07 six.49 82 8 362 1.41 0.14 six.22 364 19 1330 1.76 0.09 6.42,0.0001,0.0001,0.0001 7259 9304 4166 35.0 44.9 20.1 5216 7076 2618 35.0 47.five 17.six 2222 2727 871 38.2 46.9 15.0 7438 9803 3489 35.9 47.3 16.eight 5611 5370 3568 6180 27.1 25.9 17.2 
29.8 3607 3901 2583 4819 24.2 26.2 17.three 
32.three 1371 1573 926 1950 23.six 27.0 15.9 33.five 4978 5474 3509 6769 24.0 26.4 16.9 32.7,0.0001 7439 13290 35.9 64.1 4942 9968 33.two 66.9 2497 3323 42.9 57.1 7439 13291 35.9 64.1,0.0001 # With no T2DM n % With T2DM n % Total n % p-value 0.99 % 8185 6629 5915 65.0 39.five 32.0 28.5 14.six 6301 4427 4182 64.eight 42.three 29.7 28.1 15.five 1884 2202 1734 68.9 32.4 37.eight 29.8 ten.8 8185 6629 5916 65.9 39.5 32.0 28.five 14.five,0.0001 0.99 Chi-square test in comparison to total COPD; #:Two sample t-test; `:Fisher precise test { The urbanization level was categorized by the population density of the residential area into 4 levels, with level 1 as the most urbanized and level 4 as the least urbanized. &NTD: New Taiwan dollar. doi:10.1371/journal.pone.0098290.t001 years and the COPD with T2DM cohort had a significantly higher mean age of 68.9 years. Among the three cohorts, the majority of patients were male. Compared to control cohort, patients with COPD tended to live in lower urbanized levels and had lower income. Patients with COPD also had a higher prevalence of all comorbidities than that of the control cohort. The mean duration of follow-up for control cohort was 8.24 years, approximately 1 year longer than that for COPD without T2DM, and COPD with T2DM. As shown in figure 1, the cumulative incidence of lung cancer estimated by KaplanMeier analysis revealed significant differences among the three cohorts over follow-up period. The cumulative incidence rate was much higher in COPD patients without T2DM than in those in the COPD with T2DM and control cohort. In addition, the higher rate also observed in the COPD with T2DM than control cohort. Following a 14-year follow-up, a high incidence rate of lung cancer was observed in the COPD cohorts without and with T2DM compared with the control cohort. Furthermore, the total COPD cohort, the COPD without T2DM cohort, and COPD with T2DM cohort Lung Cancer Risk in COPD with/without T2DM Furthermore, there was a significant reduction in the risk of lung cancer in subjects with an urbanization level of 2 or a monthly income,15,000 New Taiwan Dollars. Discussion To the best 18297096 of our knowledge, this study, examining a large population cohort in Taiwan during a 14-year follow-up period is the first to investigate the risks of lung cancer in patients diagnosed with COPD either with or without T2DM. One key finding of this study was that, there was a significantly higher incidence of lung cancer among COPD patients compared to that of the general population. Further analyses indicated that there was a significantly protective effect from lung cancer of diabetic patients than non-diabetic patients among patients with COPD. Several studies have shown increased risk of lung cancer in patients with COPD. Most of them concluded that COPD is an independent risk factor. 301353-96-8 However, the causal relationship between COPD and lung carcinogenesis is not yet fully understood. COPD can be exacerbated by pulmonary infections that cause inflammation, which AKT inhibitor 2 site contributes to carcinogenesis by generating reactive oxygen or nitrogen species, increasing cellular proliferation, upregulating antiapoptotic pathways, and stimulating angiogenesis. Infection can also promote airway remodeling tha.1.89 0.07 six.49 82 eight 362 1.41 0.14 6.22 364 19 1330 1.76 0.09 6.42,0.0001,0.0001,0.0001 7259 9304 4166 35.0 44.9 20.1 5216 7076 2618 35.0 47.five 17.6 2222 2727 871 38.2 46.9 15.0 7438 9803 3489 35.9 47.three 16.8 5611 5370 3568 6180 27.1 25.9 17.2 29.8 3607 3901 2583 4819 24.2 26.two 17.three 32.3 1371 1573 926 1950 23.six 27.0 15.9 33.five 4978 5474 3509 6769 24.0 26.4 16.9 32.7,0.0001 7439 13290 35.9 64.1 4942 9968 33.two 66.9 2497 3323 42.9 57.1 7439 13291 35.9 64.1,0.0001 # With out T2DM n % With T2DM n % Total n % p-value 0.99 % 8185 6629 5915 65.0 39.five 32.0 28.5 14.6 6301 4427 4182 64.8 42.3 29.7 28.1 15.five 1884 2202 1734 68.9 32.4 37.8 29.eight 10.eight 8185 6629 5916 65.9 39.five 32.0 28.five 14.five,0.0001 0.99 Chi-square test compared to total COPD; #:Two sample t-test; `:Fisher exact test { The urbanization level was categorized by the population density of the residential area into 4 levels, with level 1 as the most urbanized and level 4 as the least urbanized. &NTD: New Taiwan dollar. doi:10.1371/journal.pone.0098290.t001 years and the COPD with T2DM cohort had a significantly higher mean age of 68.9 years. Among the three cohorts, the majority of patients were male. Compared to control cohort, patients with COPD tended to live in lower urbanized levels and had lower income. Patients with COPD also had a higher prevalence of all comorbidities than that of the control cohort. The mean duration of follow-up for control cohort was 8.24 years, approximately 1 year longer than that for COPD without T2DM, and COPD with T2DM. As shown in figure 1, the cumulative incidence of lung cancer estimated by KaplanMeier analysis revealed significant differences among the three cohorts over follow-up period. The cumulative incidence rate was much higher in COPD patients without T2DM than in those in the COPD with T2DM and control cohort. In addition, the higher rate also observed in the COPD with T2DM than control cohort. Following a 14-year follow-up, a high incidence rate of lung cancer was observed in the COPD cohorts without and with T2DM compared with the control cohort. Furthermore, the total COPD cohort, the COPD without T2DM cohort, and COPD with T2DM cohort Lung Cancer Risk in COPD with/without T2DM Furthermore, there was a significant reduction in the risk of lung cancer in subjects with an urbanization level of 2 or a monthly income,15,000 New Taiwan Dollars. Discussion To the best 18297096 of our knowledge, this study, examining a large population cohort in Taiwan during a 14-year follow-up period is the first to investigate the risks of lung cancer in patients diagnosed with COPD either with or without T2DM. One key finding of this study was that, there was a significantly higher incidence of lung cancer among COPD patients compared to that of the general population. Further analyses indicated that there was a significantly protective effect from lung cancer of diabetic patients than non-diabetic patients among patients with COPD. Several studies have shown increased risk of lung cancer in patients with COPD. Most of them concluded that COPD is an independent risk factor. However, the causal relationship between COPD and lung carcinogenesis is not yet fully understood. COPD can be exacerbated by pulmonary infections that cause inflammation, which contributes to carcinogenesis by generating reactive oxygen or nitrogen species, increasing cellular proliferation, upregulating antiapoptotic pathways, and stimulating angiogenesis. Infection can also promote airway remodeling tha.
