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

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Abstract

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; I2 = 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; I2 = 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; I2 = 0%), while there was no association in diabetic men (RR, 1.07; 95% CI, 0.89–1.28; I2 = 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; I2 = 0%), studies controlling for major confounding variables such as age, smoking and alcohol (RR, 1.19; 95% CI, 1.00–1.43; I2 = 23.1%), studies with long-term follow-up (RR, 1.14; 95% CI, 1.08–1.20; I2 = 0%), and high-quality studies assessed by the Newcastle–Ottawa Scale (RR, 1.14; 95% CI, 1.08–1.20; I2 = 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.

Introduction

Lung cancer is the most common cancer and the leading cause of cancer-related deaths globally.1 Despite enormous efforts to develop screening and treatment modalities, the 5-year survival rate for lung cancer is as low as 15%.2 Preventive strategies that manage risk factors have been implicated to reduce the incidence and mortality of lung cancer. The role of cigarette smoking in lung cancer development is well known, however smoking does not explain all of the variance in disease distribution.3, 4 As around 20% of women who develop lung cancer have never smoked, other risk factors should be considered.5

Diabetes mellitus is serious and becoming increasingly common in many countries worldwide.6 It has recently been suggested that diabetes increases the risk of a variety of cancers, including breast,7 pancreatic,8 colorectal9 and kidney cancer.10 However, epidemiologic studies of the relationship between diabetes and lung cancer have shown inconsistent results. The main issue in evaluating diabetes and lung cancer risk is the possible confounding effects of smoking and sex. Smoking is associated with diabetes,11, 12 and is the most important risk factor for lung cancer among both men and women.3, 4 Therefore, the analysis should be performed after controlling for smoking status in order to determine whether diabetes is an independent risk factor for lung cancer. Moreover, subgroup analysis by sex should be considered as the characteristic of lung cancer and differ for men and women.13

The possible role of diabetes is of particular importance in lung cancer prevention as the prevalence of diabetes worldwide is expected to approximately double between 2000 and 2030.6 This study was designed to perform a meta-analysis of observational studies to evaluate the association between diabetes and lung cancer. In this analysis, we focused on the direct effects of diabetes on lung cancer aetiology, independent of smoking and whether any association is dependent on sex.

Section snippets

Search strategy

Studies investigating the association between diabetes mellitus and lung cancer risk were identified by a literature search of MEDLINE (PubMed), EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL), from when recording began up to September 2012. Our overall search strategy included terms for diabetes (diabetes, diabetes mellitus and glucose), cancer (cancer, carcinoma, neoplasm and tumour), outcomes (incidence, risk and ratio) and study design (case–control, cohort, cohorts

Results

Fig. 1 shows a flow diagram of how we selected relevant studies. The search strategy identified 7442 references. After excluding duplicate articles, titles and abstracts of all identified studies were reviewed to exclude those that were clearly irrelevant. Next, the full texts of the remaining articles were examined for compliance with the aforementioned criteria. We identified 34 relevant publications for detailed evaluation and inclusion in the meta-analysis. After examining these articles in

Discussion

In this study, we evaluated the effect of diabetes on lung cancer incidence by using the results of previous observational studies. Diabetes was associated significantly with an increased risk of lung cancer when the analysis was restricted to studies adjusting for smoking status. When stratifying by sex, increased risks of lung cancer were prominent in diabetic women, while there was no significant association in diabetic men. In addition, significantly increased risks of lung cancer were

Contributors

S.M.P. was responsible for the study concept, design and literature search. J.-Y.L. and I.J. collected data. J.-Y.L. and J.M.L. did the statistical analysis. J.-Y.L., I.J. and S.M.P. drafted the manuscript. J.-M.Y. and S.M.P. supervised the study. All authors participated in analysis and interpretation of data and critical revision of manuscript.

Conflict of interest statement

None declared.

Funding/support

This study was not funded or supported by any organisation.

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