Genetic polymorphisms in <it>MMP 2, 9 </it>and <it>3 </it>genes modify lung cancer risk and survival

• Main Authors: González-Arriaga Patricia, Pascual Teresa, García-Alvarez Arturo, Fernández-Somoano Ana, López-Cima M Felicitas, Tardón Adonina
• Format: Article
• Language: English
• Published: BMC 2012-03-01
• Series: BMC Cancer
• Online Access: http://www.biomedcentral.com/1471-2407/12/121

<p>Abstract</p> <p>Background</p> <p>Matrix metalloproteases (MMPs) are proteolytic enzymes that contribute to all stages of tumour progression, including the later stages of invasion and metastasis. Genetic variants in the <it>MMP </it>genes may influence the biological function of these enzymes and change their role in carcinogenesis and progression. We have investigated the association between the -735 C/T, the -1171 5A/6A, and the -1562 C/T polymorphisms in the <it>MMP2, MMP3 </it>and <it>MMP9 </it>genes, respectively, and the risk and survival of lung cancer.</p> <p>Methods</p> <p>The case-control study includes 879 lung cancer patients and 803 controls from a Caucasian population in Spain (CAPUA study). Genotypes were determined by PCR-RFLP. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression. The Kaplan-Meier method, long-rank test and Cox's were used for the survival analysis.</p> <p>Results</p> <p>The <it>MMP9 </it>-1562 T/T genotype was associated with a statistically significant decreased risk of developing lung cancer (OR = 0.23; 95% CI: 0.06-0.85), whereas no association was found for the <it>MMP2 </it>-735 C/T and <it>MMP3 </it>-1171 5A/6A polymorphisms. The <it>MMP2 </it>-735 T/T genotype was statistically significantly associated with a decreased survival in non-small cell lung cancer (NSCLC) patients, identified as an independent prognosis factor of survival (hazard ratio (HR) = 1.79; 95% CI: 1.00-3.20). In contrast, no association was found between the <it>MMP3 </it>-1171 5A/6A and the <it>MMP9 </it>-1562 C/T polymorphisms and survival.</p> <p>Conclusions</p> <p>These findings support the hypothesis that the <it>MMP9 </it>-1562 C/T polymorphism is associated with a protective effect against the development of lung cancer and suggest that the <it>MMP2 </it>-735 C/T polymorphism modify the length of survival in NSCLC patients.</p>