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Polymorphism +17 C/G in matrix metalloprotease MMP8 decreases lung cancer risk
Patricia González-Arriaga1, M Felicitas López-Cima, Ana Fernández-Somoano
1Departamento de Medicina, Unidad de Epidemiología Molecular del Instituto Universitario de Oncología, Universidad de Oviedo, Oviedo, Spain. laboepic.uo@uniovi.es
Background:
Matrix metalloproteases (MMPs) constitute a family of enzymes capable of degrading different components of the extracellular matrix and are implicated in the invasion of tumor cells through the basement membrane. Polymorphisms in MMP genes may result in changes in the expression of MMPs being associated with the development and progression of cancer. We have investigated the association between three polymorphisms (-1607 1G/2G, +17 C/G and -77 A/G) in the human collagenases MMP1, MMP8 and MMP13 and the risk of development or progression of lung cancer.
Methods:
A hospital-based case-control study was designed including 501 lung cancer patients and 510 controls matched. Genotypes were determined by PCR-RFLP. Results were analyzed using unconditional logistic regression, Cox's proportional hazard regression, and the Kaplan-Meier method.
Results:
The MMP1 and MMP13 promoter polymorphisms were not associated with lung cancer risk, while the C/G polymorphism in MMP8 was associated with a statistically significant decreased risk of developing lung cancer (ORadj = 0.65; 95%CI = 0.45-0.93). The Kaplan-Meier analysis showed that the polymorphisms in MMP1, MMP8 and MMP13 not seem to modify the overall survival. Multivariate analysis revealed that MMP1, MMP8 and MMP13 polymorphisms are not independent prognostic factors for overall survival.
Conclusion:
This study suggests that the polymorphism in MMP8 is associated with a decreased lung cancer risk, which can be used as a prognostic marker in lung cancer.
Insights
Genetic variations in matrix metalloproteinase genes (MMPs) may influence cancer risk. A study found a specific MMP8 gene polymorphism is associated with a reduced risk of developing lung cancer, suggesting its potential as a prognostic marker.
Area of Science:
- Genetics and Oncology
- Molecular Biology
- Cancer Research
Background:
- Matrix metalloproteinases (MMPs) degrade extracellular matrix, aiding tumor cell invasion.
- Genetic variations (polymorphisms) in MMP genes can alter MMP expression, influencing cancer development.
- Investigated associations between MMP1, MMP8, and MMP13 gene polymorphisms and lung cancer risk/progression.
Purpose of the Study:
- To examine the relationship between specific polymorphisms in MMP1, MMP8, and MMP13 genes and the risk of developing or progressing lung cancer.
- To determine if these MMP gene polymorphisms impact overall survival in lung cancer patients.
Main Methods:
- Hospital-based case-control study with 501 lung cancer patients and 510 controls.
- Genotyping performed using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP).
- Statistical analysis included logistic regression, Cox's proportional hazard regression, and Kaplan-Meier survival analysis.
Main Results:
- MMP1 and MMP13 polymorphisms showed no association with lung cancer risk.
- A specific MMP8 C/G polymorphism was linked to a statistically significant decrease in lung cancer risk (ORadj = 0.65).
- Polymorphisms in MMP1, MMP8, and MMP13 did not appear to affect overall survival and were not independent prognostic factors.
Conclusions:
- The investigated MMP8 gene polymorphism is associated with a reduced risk of developing lung cancer.
- This MMP8 polymorphism may serve as a potential prognostic marker for lung cancer.
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