Research article

Polymorphism +17 C/G in Matrix Metalloprotease MMP8 decreases lung cancer risk

Patricia González-Arriaga¹ , M Felicitas López-Cima¹ , Ana Fernández-Somoano¹ , Teresa Pascual² , Manuel G Marrón² , Xose S Puente³ and Adonina Tardón¹

¹  Departamento de Medicina, Unidad de Epidemiología Molecular del Instituto Universitario de Oncología, Universidad de Oviedo, 33006 Oviedo, Spain and CIBER Epidemiología y Salud Pública (CIBERESP), Spain

²  Servicio de Neumología, Hospital de Cabueñes, Gijón, Spain

³  Departamento de Bioquímica y Biología Molecular, Instituto Universitario de Oncología del Principado de Asturias, Universidad de Oviedo, 33006 Oviedo, Spain

author email corresponding author email

BMC Cancer 2008, 8:378doi:10.1186/1471-2407-8-378

Published:	19 December 2008

Abstract

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.