Association of asthma and lung cancer risk: A pool of cohort studies and Mendelian randomization analysis.

BACKGROUND: Over the past 2 decades, population-based studies have shown an increased association between asthma and the risk of lung cancer. However, the causal links between these 2 conditions remain poorly understood. METHODS: We conducted a comprehensive search of various databases, including PubMed, Embase, Web of Science, and Cochrane Library, up until May 04, 2023. Only articles published in English were included in our study. We performed a meta-analysis using random-effects models to calculate the odds ratio (OR) and corresponding 95% confidence interval (CI). Subgroup analyses were conducted based on study design, gender, and histologic types. We also conducted a 2-sample Mendelian randomization (MR) using the genome-wide association study pooled data (408,422 people) published by the UK Biobank to explore further the potential causal relationship between asthma and lung cancer. RESULTS: Our meta-analysis reviewed 24 population-based cohort studies involving 1072,502 patients, revealing that asthma is significantly associated with an increased risk of lung cancer (OR = 1.29, 95% CI 1.19-1.38) in all individuals. Subgroup analysis showed a significantly higher risk of lung cancer in females with asthma (OR = 1.23, 95% CI 1.01-1.49). We found no significant association between asthma and lung adenocarcinoma (LUAD) (OR = 0.76, 95% CI 0.54-1.05), lung squamous carcinomas (LUSC) (OR = 1.09, 95% CI 0.79-1.50), or small-cell lung cancer (SCLC) (OR = 1.00, 95% CI 0.68-1.49). Interestingly, our MR analysis supported an increasing causality between asthma and lung cancer (OR = 1.11, 95% CI 1.04-1.17, P = .0008), specifically in those who ever smoker (OR = 1.09, 95% CI 1.01-1.16, P = .0173) and LUSC pathological type (OR = 1.15, 95% CI 1.05-1.26, P = .0038). CONCLUSION: Through meta-analysis, our study confirms that patients with asthma have a higher risk of developing lung cancer. Our MR study further support an increasing causal relationship between asthma and the risk of lung cancer, particularly in smokers and LUSC. Future studies examining the link between asthma and the risk of developing lung cancer should consider the bias of controlled and uncontrolled asthma.

The associations of alcoholic liver disease and nonalcoholic fatty liver disease with bone mineral density and the mediation of serum 25-Hydroxyvitamin D: A bidirectional and two-step Mendelian randomization.

BACKGROUND: Reduced bone mineral density (BMD) and osteoporosis are common in chronic liver diseases. However, the causal effect of alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) on BMD remains uncertain. OBJECTIVES: This study uses a two-sample Mendelian randomization (MR) design to evaluate the genetically predicted effect of ALD and NAFLD on BMDs using summary data from publically available genome-wide association studies (GWASs). METHODS: The GWAS summary statistics of ALD (1416 cases and 213,592 controls) and NAFLD (894 cases and 217,898 controls) were obtained from the FinnGen consortium. BMDs of four sites (total body, n = 56,284; femoral neck, n = 32,735; lumbar spine, n = 28,498; forearm, n = 8143) were from the GEnetic Factors for OSteoporosis Consortium. Data for alcohol consumption (n = 112,117) and smoking (n = 33,299) and serum 25-Hydroxyvitamin D (25-OHD) level (n = 417,580) were from UK-biobank. We first performed univariate MR analysis with the Inverse Variance Weighted (IVW) method as the primary analysis to investigate the genetically predicted effect of ALD or NAFLD on BMD. Then, multivariate MR and mediation analysis were performed to identify whether the effect was mediated by alcohol consumption, smoking, or serum 25-OHD level. RESULTS: The MR results suggested a robust genetically predicted effect of ALD on reduced BMD in the femoral neck (FN-BMD) (IVW beta = -0.0288; 95% CI: -0.0488, -0.00871; P = 0.00494) but not the other three sites. Serum 25-OHD level exhibited a significant mediating effect on the association between ALD and reduced FN-BMD albeit the proportion of mediation was mild (2.21%). No significant effects of NAFLD, alcohol consumption, or smoking on BMD in four sites, or reverse effect of BMD on ALD or NAFLD were detected. CONCLUSION: Our findings confirm the genetically predicted effect of ALD on reduced FN-BMD, and highlight the importance of periodic BMD and serum 25-OHD monitoring and vitamin D supplementation as needed in patients with ALD. Future research is required to validate our results and investigate the probable underlying mechanisms.

Construction and validation of a fatty acid metabolism-related gene signature for predicting prognosis and therapeutic response in patients with prostate cancer.

Background: Reprogramming of fatty acid metabolism is a newly-identified hallmark of malignancy. However, no studies have systematically investigated the fatty acid metabolism related-gene set in prostate cancer (PCa). Methods: A cohort of 381 patients with gene expression and clinical data from The Cancer Genome Atlas was used as the training set, while another cohort of 90 patients with PCa from GEO (GSE70769) was used as the validation set. Differentially expressed fatty acid metabolism-related genes were subjected to least absolute shrinkage and selection operator (LASSO)-Cox regression to establish a fatty acid metabolism-related risk score. Associations between the risk score and clinical characteristics, immune cell infiltration, tumor mutation burden (TMB), tumor immune dysfunction and exclusion (TIDE) score, and response to chemotherapy were analyzed. Finally, the expression level of genes included in the model was validated using real-time PCR. Results: A prognostic risk model based on five fatty acid metabolism related genes (ALDH1A1, CPT1B, CA2, CROT, and NUDT19) were constructed. Tumors with higher risk score were associated with larger tumor size, lymph node involvement, higher Gleason score, and poorer biochemical recurrence (BCR)-free survival. Furthermore, the high- and low-risk tumors exhibited distinct immune cell infiltration features and immune-related pathway activation. High-risk tumors were associated with favorable response to immunotherapy as indicated by high TMB and low TIDE score, but poor response to bicalutamide and docetaxel chemotherapy. Conclusion: This study established a fatty acid metabolism-related gene signature which was predictive of BCR and response to chemotherapy and immunotherapy, providing a novel therapeutic biomarker for PCa.