Association of Metabolic Syndrome With Risk of Lung Cancer: A Population-Based Prospective Cohort Study

Abstract

Background: Both the incidence of lung cancer and the prevalence of metabolic syndrome (MetS) have been increasing worldwide. The relationship between MetS and lung cancer remains controversial.

Research question: What is the risk of lung cancer associated with MetS and its components?

Study design and methods: Multivariable Cox regression models were used to estimate the hazard ratio (HR) of MetS-related variables on lung cancer risk, both overall and by histologic subtype, in the UK Biobank. Stratified analyses were conducted by sex, tobacco use status, and use of medication. HR curves were used to test the nonlinear associations between the metabolic markers and the risk of lung cancer.

Results: Of the 331,877 participants included in this study, a total of 77,173 participants had a diagnosis of MetS at enrollment. During a median follow-up of 10.9 years, lung cancer as the primary site developed in 2,425 participants. The HRs of MetS were 1.21 (95% CI, 1.09-1.33), 1.28 (95% CI, 1.10-1.50), and 1.16 (95% CI, 0.94-1.44) for the overall risk of lung cancer, adenocarcinoma, and squamous cell carcinoma, respectively. The HRs increased with the number of metabolic abnormalities from 1.11 to approximately 1.4 or 1.5 for those with one to five disorders. Positive association with lung cancer was observed for low high-density lipoprotein cholesterol (HDL-C), elevated waist circumference, and hyperglycemia. The relationship between MetS and lung cancer was modified by sex, with a stronger effect in female patients (P = .031). The risk of lung cancer resulting from MetS was elevated mainly among individuals who used tobacco, although the modification effect of tobacco use was not statistically significant. A nonlinear association was found between lung cancer and HDL-C, waist circumference, and glycated hemoglobin.

Interpretation: The increased risk of lung cancer associated with MetS suggests the importance of taking metabolic status and markers into consideration for the primary prevention of lung cancer and the selection of high-risk populations for lung cancer screening.

Keywords: elevated waist circumference; hyperglycemia; low HDL-C; lung cancer; metabolic syndrome.

Figure 1

Forest plot showing the association of MetS-related variables with risk of lung cancer stratified by sex. P < .05 (interaction analysis) indicates statistically significant effect modifications. HDL-C = high-density lipoprotein cholesterol; HR = hazard ratio; MetS = metabolic syndrome.

Figure 2

Forest plot showing the association of MetS-related variables with risk of lung cancer stratified by tobacco use status. P < .05 (interaction analysis) indicates statistically significant effect modifications. HDL-C = high-density lipoprotein cholesterol; HR = hazard ratio; MetS = metabolic syndrome.

Figure 3

A-F, Funnel plots showing the nonlinear association between biomarkers of metabolic syndrome with risk of lung cancer: systolic BP (A), diastolic BP (B), triglycerides (C), HDL-C (D), waist circumference (E), and HbA1c (F). HbA1c = glycated hemoglobin; HDL-C = high-density lipoprotein cholesterol; HR = hazard ratio.