Elevated Levels of the Cancer Marker Neuron-Specific Enolase in a Patient With Coexisting Silicosis and Sarcoidosis.

In a periodical medical checkup, a 39-year-old Mongolian underground miner was diagnosed with silicosis based on chest radiography, computed tomography (CT), and work history. Chest radiography showed diffuse bilateral rounded nodules in both lung fields, with upper lobe dominance and large opacities in the right upper zone. Chest CT presented conglomerated massive changes in the right upper lobe and the coalescence of small nodules in the left upper lung. In the blood test, serum levels of the lung cancer marker neuron-specific enolase (NSE) were elevated (24.58 ng/mL). Carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA 21-1) levels were within the reference range. Subsequent to the suspicion of a tumour in the right upper lobe, a right upper lobectomy was performed. The histopathological examination of the lung specimen revealed the coalescence of numerous silica nodules, accompanied by indications of associated sarcoidosis. The histological features suggested the presence of two concurrent pathological processes: silicosis and sarcoidosis. This case demonstrated the combination of three clinical conditions diagnosed in one patient, including complicated silicosis associated with sarcoidosis and elevated serum NSE levels. This case report may serve as a foundation for future investigations exploring the potential of NSE as a marker for silicosis.

SNP-SNP positive interaction between MMP2 and MMP12 increases the risk of COPD.

Determining SNP-SNP interaction of the disease has become important for further investigation of pathogenesis and experimental research. Although many studies have been published on the effect of MMPs gene polymorphisms on chronic obstructive pulmonary disease (COPD), there is a lack of information on SNP-SNP and SNP-environment interactions. This study aimed to investigate the interaction between the polymorphisms of MMP1, MMP2, MMP9 and MMP12 genes and its combined effect with smoking on the risk of developing COPD. Totally 181 COPD patients and 292 healthy individuals were involved. Blood samples from the participants were tested for genotyping and data were collected through questionnaires. Genotyping was performed with nested allele-specific polymerase chain reaction (AS-PCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). SNP-SNP and SNP-environment interactions were investigated using multifactor dimensionality reduction and logistic regression analysis. The result showed that participants with high nicotine dependence and heavy smokers had a higher risk of COPD than non-smokers. Also, G/G genotype (cOR = 5.83; 95% CI, 1.19-28.4, p = 0.029) of MMP2 rs243864 and T/T genotype (cOR = 1.79; 95% CI, 1.16-2.76, p = 0.008) of MMP12 rs652438 independently contributes to the susceptibility of COPD. For SNP-SNP interaction, the positive interaction between rs243864 G/G genotype of MMP2 and rs652438 T/T genotype of MMP12 was found, and the combination of risk genotypes has a high risk of COPD (OR = 12.92; 95% CI, 1.46-114.4, p = 0.021). Moreover, the combination of T/T genotype of MMP12 rs652438 and smoking-related factors increases the risk of COPD approximately 4.5 to 6-fold. The results suggests that there is a combination of MMP2, MMP12, and smoking-related factors may increase the risk of developing COPD.

The Cumulative Effect of Gene-Gene Interactions Between GSTM1, CHRNA3, CHRNA5 and SOD3 Gene Polymorphisms Combined with Smoking on COPD Risk.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a multifactorial disorder which is affected by external and internal risk factors. People with no external risk factors may be significantly affected and develop pulmonary disease. The study aimed to define gene-gene and gene-environmental effects on COPD. METHODS: A case control study involved 181 COPD patients and 292 healthy individuals, with peripheral blood sampling and adequate questionnaires. Genotyping was done with various types of PCR design for GSTM1 (null del), GSTT1 (null del), EPHX1 (rs2234922 and rs1051740), GSTP1 (rs1695 and rs1138272), CHRNA3 (rs1051730 and rs12914385), CHRNA5 (rs16969968 and rs17486278), and SOD3 (rs1799895 and rs699473) gene polymorphisms. Gene-gene and gene-environmental interactions were investigated using multidimensional regression analysis. RESULTS: Frequency of risk alleles of rs1051730 (p = 0.001), rs16969968 (p <0.001), and rs1799895 (p <0.001) polymorphisms were significant in univariate analysis. For gene-gene interaction, GSTM1 null, rs1051730, rs16969968, and rs1799895 polymorphisms independently contributed to risk of COPD and any combinations of the risk genotypes have a higher risk of disease. A cumulative effect of the four risk polymorphisms increased the risk of COPD for the smoking index (cOR = 13.6, p <0.001), cigarettes per day (cOR = 32.08, p <0.01), nicotine dependence (cOR = 12.0, p <0.01), and smoking status (cOR = 17.02, p <0.01) for gene-environmental interaction. CONCLUSION: Several pivotal genes showed distinct effects for COPD, and some synergistic effects affected the disease progression. The development of COPD was synergistically increased with gene-gene and gene-environmental risk factors.