Based on this large, population‐based, cross‐sectional study, we recognized that elevated SBP and high WC was associated with PNs development. When considered jointly, the number of abnormal MetS components was linearly associated with increased PNS risk. Remarkably, individuals with ≥3 MetS components had an approximately 40% increased risk of PNs than those with no MetS components. In addition, individuals with MetS had an approximately 30% increased risk of PNs than those who did not meet the MetS diagnostic criteria (number of MetS components<3). To the best of our knowledge, this is the first large-scale cross-sectional study to demonstrate the relationship between MetS components and PNs risk in china. The results provide strong evidence to support the potential impact of MetS components on the increased risk of PNs.
Previous studies have reported that some components of MetS were associated with lung cancer. The increased risk of PNs in individuals with high WC in our study was consistent with that observed in previous. The European Investigation Into Cancer and Nutrition (EPIC) showed that compared with individuals with similar BMIs and normal WC, those with a greatly higher WC (≥94 cm for men, ≥88 cm for women) had a HR of 1.25 (95% CI: 1.05, 1.50). A pooled analysis of 12 cohort studies involving more than 1.6 million individuals globally with an average 12-year follow-up found that WC and WHR were associated with increased lung cancer risk, regardless of sex, smoking status, follow-up time, and tumor histology. Even when considering BMIs, participants with BMIs of less than 25 kg/m2 but higher WC had a 40% greater risk (HR = 1.40, 95% CI: 1.26 - 1.56) than those with BMIs of 25 kg/m2 or greater but normal/moderate WC. Consequently, abdominal obesity is a part of MetS, which requires us to improve diet and increasing physical exercise.
A follow-up study in Finland provided evidence that both SBP and DBP were weighty predictors of lung cancer, with a 10% increase in risk every 10-mmHg rise in blood pressure. Among smokers, the age-adjusted hazard ratios for blood pressure increment of 10 mmHg are: SBP 1.11 (95% CI: 1.05, 1.17)), DBP 1.17 (95% CI: 1.05, 1.29), respectively. Similarly, a meta-analysis of 7 prospective cohort studies in Europe revealed that In men, significant linear associations in analysis per 10-mm Hg increment of mid-BP were found among men for cancers of lung (P for trend＜0.05, HR=1.09 (95% CI: 1.03 –1.16). Futher, a positive association by quintiles and 10-mm Hg increments of BP was also found for lung cancer mortality among men (p for trend＜0.05, HR=1.09 (95% CI: 1.02 –1.16). This association is basically consistent with what we found in lung nodules. After adjustment for confounders, results indicated that a positive association of high BP with PNs (OR = 1.23 (1.01–1.51), which reminds us to constantly adhere to the detection and control of blood pressure, reduce salt intake and other risk factors of hypertension.
However, inconsistent to previous studies, we did not find the significant correlation between the remaining other components and pulmonary nodules. Zhang and his collegues found that compared with males with normal TG (75-100 mg/dL), both low TG (HR=1.24, 95%CI: 0.99-1.54) and high TG (HR =1.27, 95%CI: 1.01-1.59) were correlated with increased lung cancer risk. Several longtitude prospective cohort studies indicated that the inverse association of HDL cholesterol was evident for cancers of lung despite of different explanation on the role of reverse causation[36, 37]. Regarding blood glucose, although there is no clear evidence that it is related to increased risk, it’s well known that cancer cells prefer to metabolize glucose by Warburg effect. Additionally, a study showed that low FBG levels and diabetes were associated wth poor survival in patientsits with lung cancer. Moreover, a case-cohort study of Finnish men inferred that higher fasting serum insulin concentrations, as well as the presence of insulin resistance, appear to be associated with an elevated risk of lung cancer development. Diabetes was also confirmed to be an independent predictor of the risk of recurrence following resection of NSCLC. Compared with non-diabetic controls limiting the analysis to studies adjusting for smoking status, diabetes was independently associated with the increased risk of lung cancer (RR, 1.11; 95% CI, 1.02–1.20; I2= 46.1%). Differences in race, definitions of major variables, and adjusted confounders might possibly explain these discrepancie.
The association of lung cancer risk with MetS is currently controversial. Some studies suggested there were no obvious association between MetS and lung cancer[16, 17]. In contrast, some studies indicated that MetS and/or its components are somewhat associated with a higher risk of lung cancer incidence and believed the mechanism of MetS promotes the cancer development/growth is not well defined, especially for lung cancers. Interestingly, rencent epidemiological analysis indicated that the prevalence of MeS in survivors of lung cancer showed higher prevalence of MeS compared with that of the controls without chronic disease (OR = 2.11; 95% CI = 1.33–3.36). From a genetic perspective, a review showed that genes associated with metabolic syndrome were present among genes related to susceptibility to lung adenocarcinoma in never smokers. Epidermal growth factor receptor (EGFR), vesicle transport through interaction with t-SNAREs homologue 1A gene (VTl1A), tumor necrosis factor receptor superfamily member 10C (TNFRSF10C), Chromosome 3 open reading frame 21 (C3ORF21) and hyper methylation of TNFSF10C, Basic helix-loop-helix transcription factor 5 (BHLHB5), and boule-like RNA-binding protein (BOLL) are involved in the metabolic pathways of metabolic syndrome. Our observations on the association of PNs risk with MetS yielded similar and interesting conclusions.
In addition to the genetic perspective, several potential mechanisms might explain the associations between MetS and PNs including several processes such insulin resistance, dyslipidemia, endothelial dysfunction, abnormal glucose utilization, and oxidative stress, DNA damage, Low-grade systemic inflammation, asabnormal cell proliferation etc[23, 34, 41, 42, 45]. An index case also highlighted the emerging interaction between MetS and tuberculosis. Central obesity, hypertension, hyperglycemia and the rest work together to increase risk. Hence, it need to confirm the degree of the correlation of factors that might be mediated by MetS. It need further investigations to explain the intrinsic biological mechanism underlying the correlation between MetS components and PNs.
Potential limitations of our study ought to be discussed. First, due to its observational nature, our discoveries might be influenced by measurement errors in anthropometric variables and residual confounding in covariates such as smoking exposure. Second, all participants in this study recruited from the Jidong communities in northern China, which restricts the generalization of the finding. Finally, the design of this cross‐sectional study made it difficult to evaluate the causality between MetS and PNs. In the future, we need to increase the sample size and perform a longtime follow-up examinations to compare the change of MetS components while clarifying the diagnosis of benign and malignant lung nodules.