Metabolic Syndrome Linked to Risk for Lung Cancer, Especially in Women

Metabolic syndrome (MetS) and its components are risk factors for lung cancer, with the risk greater among women, according to study findings published in Chest.

 MetS, an increasingly common syndrome that has been identified as a risk factor in cardiovascular disease and diabetes, comprises a group of interrelated conditions that include hypertension, dyslipidaemia, central obesity, and insulin resistance. Investigators sought to determine if risk for lung cancer is associated with MetS and its components, evaluating the possibility of effect modification by sex, smoking status, and medication use.

The investigators conducted a population-based prospective cohort study of individuals from the United Kingdom (UK) Biobank, a prospective cohort of more than half a million women and men, aged 37 to 73 years, recruited between 2006 to 2010 from 22 assessment centers across England, Scotland, and Wales. Among the more than 331,000 participants in the current analysis, 77,173 had MetS upon study enrollment. All participants were followed (median 10.9 years) for incidence of cancer through February 2020 in England and Wales, and through January 2021 in Scotland.

The researchers divided patients into cohorts with and without MetS; both groups had similar demographics with respect to age, sex, race, and the number of individuals who smoked/never smoked. Significantly greater proportions of individuals with vs without MetS were noted in subgroups related to obesity (60% vs 13%, respectively), antihypertensives (39% vs 18%, respectively), and lipid lowering medication (31% vs 14%, respectively).

Among the 2425 participants who developed lung cancer (with the lung as the primary cancer site), MetS was found to be a statistically significant risk factor. The hazard ratios (HRs) noted for MetS and lung cancer risk were as follows: overall lung cancer HR, 1.21 (95% CI, 1.09-1.33; adenocarcinoma HR, 1.28 (95% CI, 1.10-1.50); squamous cell carcinomaHR, 1.16 (95% CI, 0.94-1.44). The study authors noted HRs increased with the number of metabolic abnormalities, from 1.11 to approximately 1.4 to 1.5 among those with 1 to 5 disorders.

Positive associations with lung cancer were found among individuals with MetS subcomponents, including hyperglycemia (HR, 1.30; 95% CI, 1.16-1.45), elevated waist circumference (HR, 1.36; 95% CI, 1.22-1.53), and low high-density lipoprotein cholesterol (HDL-C)(HR, 1.20; 95% CI, 1.09-1.32). The investigators noted lung cancer incidence rates were higher among individuals in all MetS subcomponent subgroups, with an especially high incidence rate among those with vs without hyperglycemia (141.4/100,000 vs  64.1/100,000, respectively).

Female sex had the strongest modification effect on the relationship between MetS and lung cancer. Women vs men with MetS had higher lung cancer risk (HR, 1.38; 95% CI, 1.20-1.60 vs HR, 1.07; 95% CI, 0.93-1.23; P =.031). Among women with 5 metabolic abnormalities, risk of lung cancer was double that of women with no abnormalities. For men, having a greater number of metabolic abnormalities did not result in any kind of statistically significant trend with respect to lung cancer.

The modification effect of smoking upon risk for lung cancer due to MetS was not statistically significant, although lung cancer risk due to MetS was mostly elevated among smokers. A non-linear association existed between lung cancer and glycated hemoglobin, waist circumference, and HDL-C.

Study limitations include residual confounding and inconsistencies in biomarker measurements due to the use of non-fasting baseline blood samples.

The investigators concluded, “In this study, we found associations of MetS and its components with increased risk of lung cancer. This relationship could potentially be modified by sex and smoking.” The study authors added, “Although a causal association between MetS and lung cancer cannot be verified through this study, the evidence obtained suggests the importance of taking metabolic status and markers into the selection of high-risk populations for lung cancer screening, and highlights a new direction of lung cancer prevention.”

This article originally appeared on Pulmonology Advisor