Abstract
Purpose
Lung cancer is now one of the most common cancers in the world, with a high mortality rate and poor prognosis. Predicting the prognosis of lung cancer patients and using this information to develop treatment strategies and interventions is important for prolonging patient survival. A stratified analysis was conducted on Han Chinese primary lung cancer patients in the Chinese population, with the objective of investigating the relationship between matrix metalloproteinase 12(MMP12) gene polymorphism rs586701 and the prognosis of lung cancer patients.
Methods
A total of 888 Han Chinese primary lung cancer patients (exclusive of minors) were recruited between January and November 2009 (10 months) and provided written informed consent. The study included subjects from Changhai Hospital of the Naval Medical University (Second Military Medical University) and Taizhou Institute of Health Sciences of Fudan University. A total of 49 subjects were excluded due to incomplete data collection for various reasons. Blood samples were collected from 839 patients diagnosed with lung cancer, and genomic DNA was extracted for genotyping using SNPscan technology. In order to adjust for multiple factors, the data was stratified by age, sex, smoking status, family history of malignancy, TNM stage, and lung cancer tissue type. The association between lung cancer prognosis and genotype was then analyzed using a multivariate Cox proportional risk model.
Results
A polymorphism in the MMP12 gene, specifically the T > G variant at position 586701, has been associated with a reduction in survival time in lung cancer patients. In the overall sample, patients with the TG genotype (TG vs TT, adjusted HR = 1.21, 95% CI: 1.01–1.44, P = 0.035) exhibited a shorter survival time and a worse prognosis. Stratified analyses showed that among male lung cancer patients, lung cancer patients younger than 60 years old, and smoking lung cancer patients, patients with the TG genotype had a lower survival time than patients with the TT genotype (adjusted risk ratio HR = 1.24, 95% CI: 1.01–1.52, P = 0.04; HR = 1.58, 95% CI: 1.18–2.12, P = 0.002; HR= (1.30, 95% CI: 1.06–1.61, P = 0.013). In patients with SCC and NSCLC, survival time was shorter in patients with the TG genotype (TG vs TT, adjusted risk ratio HR = 1.48, 95% CI: 1.10–2.01, P = 0.010; HR = 1.21, 95% CI: 1.01–1.46, P = 0.038). In the designed genetic model, the dominant genotype TG + GG was associated with a shorter survival time and worse prognosis among lung cancer patients aged less than 60 years (TG + GG vs TT, adjusted risk ratio HR = 1.43, 95% CI: 1.07–1.90, P = 0.014).
Conclusion
The MMP12 polymorphism rs586701 may be associated with the prognosis of lung cancer. Specifically, the MMP12 polymorphism rs586701 T > G has been found to lead to a worse prognosis.