Diabetes mellitus as an independent risk factor for lung cancer: A meta-analysis of observational studies

Background: Epidemiologic studies have demonstrated inconsistent associations between diabetes mellitus and the risk of lung cancer. To determine whether diabetes mellitus is associated with an increased risk of lung cancer, we performed a meta-analysis of observational studies. Methods: PubMed, EMBASE and the Cochrane Library were searched for observational studies conducted prior to September 2012. We included prospective cohort studies that reported relative risks and case-control studies that showed odds ratios in the analysis. The pooled relative risk (RR) with 95% confidence intervals (CIs) was calculated with a random effects model. Sensitivity analysis was performed with studies which controlled for smoking status. Associations were assessed in several subgroups representing different participant and study characteristics. Results: A total of 34 studies from 24 manuscripts (10 case-control studies and 24 cohort studies) were included in the analyses. Diabetes was significantly associated with the increased risk of lung cancer compared with non-diabetic controls when limiting the analysis to studies adjusting for smoking status (RR, 1.11; 95% CI, 1.02-1.20; I-2 = 46.1%). By contrast, this association disappeared when the analysis was restricted to studies not adjusting for smoking status (RR, 0.99; 95% CI, 0.88-1.11; I-2 = 96.7%). When stratifying by sex, an increased risk of lung cancer was prominent in diabetic women (RR, 1.14; 95% CI, 1.09-1.20; I-2 = 0%), while there was no association in diabetic men (RR, 1.07; 95% CI, 0.89-1.28; I-2 = 96.6%). Among diabetic women, significantly increased risks of lung cancer were found in the following subgroups: cohort studies (RR, 1.14; 95% CI, 1.08-1.20; I-2 = 0%), studies controlling for major confounding variables such as age, smoking and alcohol (RR, 1.19; 95% CI, 1.00-1.43; I-2 = 23.1%), studies with long-term follow-up (RR, 1.14; 95% CI, 1.08-1.20; I-2 = 0%), and high-quality studies assessed by the Newcastle-Ottawa Scale (RR, 1.14; 95% CI, 1.08-1.20; I-2 = 0%). Interpretation: Preexisting diabetes mellitus may increase the risk of lung cancer, especially among female diabetic patients. Further large-scale prospective studies are needed to test specifically the effect of diabetes mellitus on lung cancer risk. (c) 2013 Elsevier Ltd. All rights reserved.